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    Participants who either do not have cancer but are at high risk for developing the disease or have had cancer and are at high risk for developing a new cancer.
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    These trials look at ways to improve the quality of life of cancer patients, especially those who have side effects from cancer and its treatment. They find new ways to help people cope with pain, nutrition problems, infection, nausea and vomiting, sleep disorders, depression and other health problems.
  • open for enrollment

    Lung-MAP: S1400 Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IIIB-IV Squamous Cell Lung Cancer

    Protocol: SWOG-S1400

    Eligibility:

    Inclusion Criteria:

    • SCREENING REGISTRATION:
    • Patients must have pathologically proven squamous cell non-small cell lung cancer (NSCLC) confirmed by tumor biopsy and/or fine-needle aspiration; disease must be either advanced, incurable stage IIIB or stage IV NSCLC; the primary diagnosis of SCCA should be established using the current World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASLC)-classification of Thoracic Malignancies; the diagnosis is based on hematoxylin and eosin (H&E) stained slides with or without specific defined immunohistochemistry (IHC) characteristic (p40/p63 positive, transcription termination factor [TTF1] negative) if required for diagnosis; mixed histologies will be allowed provided that they contain >= 50% of the squamous component
    • Patients must have progressed after receiving exactly one front-line platinum containing metastatic chemotherapy regimen
    • Patients must have adequate tumor tissue available (defined as >= 20% tumor cells as confirmed by the treating institution's local pathologist); patients must agree to have this tissue submitted to Foundation Medicine for common broad platform Clinical Laboratory Improvement Amendments (CLIA) biomarker profiling; if archival tumor is used either a tumor block or at a minimum 12 formalin-fixed paraffin-embedded (FFPE) slides 4-5 microns thick are required, but 20 slides are strongly recommended; in the event that patient's archival tumor material is derived from a fine needle aspirate and the tumor material from fine needle aspirate or from core needle biopsy is exhausted a new fresh tumor biopsy will be obtained and will be formalin fixed and paraffin-embedded
    • Patients must not have a known epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) fusion; in addition, patients whose biomarker profiling results indicate the presence of an EGFR mutation or ALK fusion will be notified that they are not eligible for any of the sub-studies
    • Patients must have Zubrod performance status =< 2 documented within 28 days prior to screening registration
    • Patients must also be offered participation in banking for future use of specimens
    • Patients must be willing to provide prior smoking history
    • Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
    • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
    • SUB-STUDY ASSIGNMENT:
    • Patients whose biomarker profiling results indicate the presence of an EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion are not eligible
    • Patients must be registered to the assigned sub-study within 28 calendar days of receiving sub-study assignment from the statistical center
    • Patients must have measurable disease, documented by computed tomography (CT) or magnetic resonance imaging (MRI); the CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality; if patient has measurable disease it must assessed within 28 days prior to sub-study treatment arm randomization; pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease; non-measurable disease must be assessed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form; patients with active new disease growth in previously irradiated site are eligible
    • Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study treatment arm randomization; patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 28 days following treatment, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 14 days prior to randomization
    • Patients must have progressed after receiving exactly one front-line platinum containing metastatic chemotherapy regimen; patients must not have received any prior systemic chemotherapy or investigational drug within 21 days prior to sub-study treatment arm randomization; patients must have recovered (=< grade 1) from any side effects of prior therapy; localized palliative radiotherapy >= 14 days is allowed
    • Patient must have fully recovered from the effects of prior surgery prior to sub-study treatment arm randomization
    • Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment; concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable
    • Absolute neutrophil count (ANC) >= 1,500/mcl obtained within 28 days prior to sub-study treatment arm randomization
    • Platelet count >= 100,000 mcl obtained within 28 days prior to sub-study treatment arm randomization
    • Hemoglobin >= 9 g/dL obtained within 28 days prior to sub-study treatment arm randomization
    • Serum bilirubin =< 2 X institutional upper limit of normal (IULN) within 28 days prior to sub-study treatment arm randomization
    • Either serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transferase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x IULN within 28 days prior to sub-study treatment arm randomization (if both SGOT and SGPT are done, both must be =< 2 IULN)
    • For patients with liver metastases, bilirubin and either SGOT and SGPT must be =< 5 x IULN
    • Serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50 cc/min using the following Cockroft-Gault Formula within 28 days prior to sub-study treatment arm randomization
    • Patients must have Zubrod performance status =< 2 documented within 28 days prior to sub-study treatment arm randomization
    • Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia
    • Patients must not have documented evidence of acute hepatitis or have an active or uncontrolled infection
    • Patients must not have a known history of human immunodeficiency virus (HIV) seropositivity
    • Prestudy history and physical must be obtained within 28 days prior to sub-study treatment arm randomization
    • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
    • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
    • S1400A:
    • Patients must not have any prior exposure to immunotherapy such as, but not limited to other anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death (PD)-1, or anti-PD-L1 antibodies excluding vaccines within 28 days prior to sub-study treatment arm randomization
    • Patients must not have received or be planning to receive any anti-cancer therapy whether chemotherapy, or biologic therapy, therefore receipt of the last dose of anti-cancer therapy, (chemotherapy, endocrine therapy, targeted therapy, biologic therapy, or tumor embolization) > 21 days prior to randomization (> 14 days prior to randomization for patients who have received prior TKIs [e.g. erlotinib, gefitinib, or crizotinib] and > 42 days for nitrosoureas or mitomycin-c)
    • Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment; concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable; patients must not have received or be planning to receive any immunosuppressive medication within 28 days prior to sub-study treatment arm randomization, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
    • Patients must not have any active or prior documented autoimmune or inflammatory disease (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome) within 3 years prior to sub-study treatment arm randomization; patients with vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded
    • Patients must not have any history of primary immunodeficiency
    • Patients must not have any prior grade >= 3 immune-related adverse event (irAE) or any unresolved irAE > grade 1
    • Patients must not have any history of organ transplant that requires use of immunosuppressives
    • Patients must not have any known allergy or reaction to any component of the MEDI4736 formulation
    • Patients must not have a known history of tuberculosis
    • Patients must not have received a live attenuated vaccination within 28 days prior to sub-study treatment arm randomization
    • Patients must not have known HIV, hepatitis B or C positivity
    • S1400B:
    • Hemoglobin A1c (HbA1c) < 7% obtained within 28 days prior to sub-study treatment arm randomization
    • Fasting glucose < 125 mg/dl obtained within 28 days prior to sub-study treatment arm randomization
    • Patients must not have Type 1 or 2 diabetes which requires insulin
    • Patients must not have active or a history of small or large intestine inflammation such as Crohn's disease or ulcerative colitis
    • Patients must not require daily supplemental oxygen
    • Patients must be able to take oral medications; patients may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of GDC-0032 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
    • Patients must not be taking, nor plan to take while on protocol treatment and for 14 days post the last dose of study treatment, drugs, herbal supplements or foods that are known to be strong/moderate cytochrome p450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates
    • Patients must not have received prior treatment of docetaxel as part of frontline platinum-containing chemotherapy (S1400B)
    • S1400C:
    • Patients must not be taking within 7 days prior to sub-study treatment arm randomization, nor plan to take while on protocol treatment, CYP3A4 inhibitors and/or strong CYP3A4 inducers; moderate inhibitors or inducers of isoenzyme CYP3A4 should be avoided, but if necessary can be used with caution
    • Patients must not be taking within 7 days prior to sub-study treatment arm randomization, nor plan to take while on protocol treatment drugs that are known to prolong the QT interval
    • Patients must not have QTc > 480msec (based on the mean value of the triplicate electrocardiograms [ECGs]), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes
    • Patients must not have uncontrolled electrolyte disorders which can compound the effects of a QTc-prolonging drug (eg, hypocalcemia, hypokalemia, hypomagnesemia)
    • Patients must be able to take oral medications; patient may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of palbociclib (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
    • Patients must not have received prior treatment of docetaxel as part of frontline platinum-containing chemotherapy (S1400C)
    • S1400D:
    • Patients must be >= 25 years of age (skeleton maturation is complete)
    • Patients must not be taking, nor plan to take while on protocol treatment and for 14 days after the last dose of study treatment drugs, herbal supplements and/or foods known to modulate CYP3A4 or cytochrome p450, family 2, subfamily D, polypeptide 6 (CYP2D6) enzyme activity and drugs that are known to be CYP3A4 substrates
    • Patients must not have received Nitrosourea or mitomycin C within 42 days prior to sub-study treatment arm randomization
    • Patients must not have had any prior exposure to any agent with FGFR inhibition as its primary pharmacology
    • Patients must not have a mean resting corrected QT interval (QTc) > 450 msec obtained from 3 consecutive electrocardiograms (ECGs); any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block); nor any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
    • Patients must be able to take oral medications; patient may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of AZD4547 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
    • Patients must not have a history of hypersensitivity to active or inactive excipients of AZD4547 or drugs with a similar chemical structure or class to AZD4547
    • Patients
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  • open for enrollment

    Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

    Protocol: NRG-LU001

    Eligibility:

    Inclusion Criteria:

    • Pathologically (histologically or cytologically) proven diagnosis of stage IIIA or IIIB non-small cell lung cancer within 84 days of registration; eligible histologies include adenocarcinoma, adenosquamous, large cell carcinoma, squamous carcinoma, non-lobar and non-diffuse bronchoalveolar cell carcinoma or non-small cell lung cancer not otherwise specified [NOS])
    • Patients must have measurable disease
    • Patients must have unresectable disease, be medically inoperable, or unwilling to undergo surgical management
    • Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
    • History/physical examination, including documentation of height, weight, body surface area [BSA], and vital signs, within 30 days prior to registration
    • Computed tomography (CT) or magnetic resonance imaging (MRI) imaging of the lung and upper abdomen through the adrenal glands within 30 days prior to registration
    • MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 30 days prior to registration; note: the use of intravenous contrast is required for the MRI or CT; an MRI without contrast is only permitted if the patient has a contrast allergy
    • Whole-body fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/CT within 30 days prior to registration; note: patients must have a separate CT (see above) and an FDG-PET/CT
    • Zubrod performance status 0-1
    • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
    • Platelets >= 100,000 cells/mm^3
    • Hemoglobin >= 8.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
    • Serum creatinine within normal institutional limits or creatinine clearance must be at least 60 ml/min
    • Total bilirubin =< 1.5 x upper limit of normal (ULN) for the institution
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN for the institution
    • Alkaline phosphatase =< 2.5 x ULN for the institution
    • Serum albumin > 3.0 g/dl within 14 days prior to registration
    • For women of childbearing potential, a serum pregnancy test within 72 hours prior to registration
    • Patients with post-obstructive pneumonia are eligible provided they no longer require intravenous antibiotics at registration
    • Patients must be at least 3 weeks from prior thoracotomy (if performed)
    • If a pleural effusion is present, the following criteria must be met at registration to exclude malignant involvement (incurable M1a disease):
    • When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative
    • Effusions that are minimal (i.e. not visible under ultrasound guidance) and that are too small to safely tap are eligible
    • Women of childbearing potential and male participants must practice adequate contraception throughout the study
    • Patient must provide study specific informed consent prior to study entry

    Exclusion Criteria:

    • Patients with mixed small cell and non-small cell histologies
    • Patients with distant metastasis
    • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
    • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
    • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
    • Patients currently using metformin (metformin hydrochloride), other oral hypoglycemic agents or insulin
    • Patients with any history of allergic reaction to paclitaxel or other taxanes or carboplatin
    • Patients with a history of chronic kidney disease or lactic acidosis
    • Patients with >= 10% weight loss within the past month
    • Severe, active co-morbidity, defined as follows:
    • Diagnosis of type I or type II diabetes mellitus
    • Uncontrolled neuropathy >= grade 2 regardless of cause
    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
    • Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease
    • Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol
    • End-stage renal disease (ie, on dialysis or dialysis has been recommended)
    • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
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  • open for enrollment

    A Study of BBI608 in Combination With Gemcitabine and Nab-Paclitaxel in Adult Patients With Metastatic Pancreatic Adenocarcinoma

    Protocol: OSU-14146

    Eligibility:

    Inclusion Criteria:

    1. Signed written informed consent

    2. Patients must have histologic evidence of adenocarcinoma of the pancreas, such as a core tissue biopsy or a surgical resection specimen.

    a. Cytological evidence only is not sufficient for enrollment on this study and patients can undergo a core tissue biopsy to meet this study enrollment criterion.

    3. Patients must have metastatic disease. Baseline imaging of chest, abdomen and pelvis (CT or MRI) within 21 days prior to initiation of protocol therapy is required.

    1. Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

    2. Patients with locally advanced unresectable pancreatic ductal adenocarcinoma are excluded.

    4. Patients are allowed to have up to one prior line of systemic therapy in the adjuvant setting ONLY. No prior systemic therapy in the metastatic or locally advanced/unresectable setting is allowed. Toxicities related to prior therapy must have completely resolved (except for alopecia and anemia), or be deemed irreversible.

    1. Patients who received Gemcitabine-based therapy in an adjuvant setting will be allowed to be enrolled on the trial as long as their last Gemcitabine administration was at least 6 months prior to the first dose of BBI608.

    2. Prior treatment with radiotherapy is allowed.

    5. = 18 years of age.

    6. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status < 1.

    7. Male or female patients of child-producing potential agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last BBI608 dose.

    8. Females of childbearing potential have a negative serum pregnancy test (preceding 72 hours of first day of BBI608 treatment).

    9. Patients with biliary or gastro-duodenal obstruction must have drainage or surgical bypass prior to starting chemotherapy.

    10. Significant or symptomatic amount of ascites should be drained prior to first dose of BBI608.

    11. Patients on Coumadin anticoagulation may be enrolled for as long as they undergo weekly international normalized ratio (INR) checks for the first 2 months of therapy.

    a. Patients who switch to low molecular weight heparin may be enrolled and weekly INR labs are not mandated for these patients.

    12. Aspartate transaminase (AST) level < 2.5 x upper limit of normal (ULN) and alanine transaminase (ALT) < 2.5 × upper limit of normal (ULN). For patients with liver metastases, AST < 5 ULN, and AST < 5 ULN may be enrolled if agreed upon by the investigator and medical monitor for the sponsor.

    13. Patients must have a total bilirubin level < 1.5 x ULN (= 2 x ULN if it is non-rising for a period of 10 days prior to initiation of therapy)

    14. Creatinine level < 1.0 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above or below the institutional normal (as determined by Cockcroft-Gault equation). For patients with a Body Mass Index (BMI) > 30 kg/m^2, lean body weight should be used to calculate the glomerular filtration rate (GFR).

    15. Hemoglobin (Hgb) = 9 g/dl

    16. Absolute neutrophil count = 1.5 x 10^9/L

    17. Platelets = 100 x 10^9/L

    18. Acceptable coagulation studies as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (+/-15%).

    19. Patient has no clinically significant abnormalities on urinalysis results.

    20. Life expectancy estimated at = 3 months.

    Exclusion Criteria:

    1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 14 days of the first dose of BBI608. Patients may begin BBI608 on a date determined by the investigator and medical monitor for the sponsor after a minimum of 14 days since last receiving anti-cancer treatment, provided that all treatment-related adverse events have resolved or have been deemed irreversible.

    2. Patients with islet cell neoplasms will be excluded.

    3. Major surgery, other than diagnostic surgery (e.g., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to first dose.

    4. Any brain metastases including leptomeningeal metastases, are excluded, even if treated and stable.

    5. History of posterior reversible encephalopathy syndrome.

    6. Neurosensory neuropathy = grade 2 at baseline.

    7. Pregnant or breastfeeding.

    8. Significant gastrointestinal disorder(s) that would, in the opinion of the Principal Investigator, prevent absorption of an orally available agent (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection and small intestinal resection).

    9. Unable or unwilling to swallow BBI608 capsules daily.

    10. Uncontrolled chronic diarrhea = grade 2 at baseline.

    11. Uncontrolled intercurrent illness including, but not limited to uncontrolled active infection (including bacterial, viral or fungal requiring systemic therapy), clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.

    12. Known infection with Human Immunodeficiency Virus (HIV), and/or active infection with hepatitis B, or hepatitis C.

    13. Significant cardiac disease, including the following: unstable angina, New York Heart Association class III-IV congestive heart failure, myocardial infarction within six months prior to study enrollment.

    14. History of active Peripheral Artery Disease (treated peripheral artery disease that is stable for at least 6 months is allowed).

    15. Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.

    16. History of hemolytic-uremic syndrome.

    17. History of other active malignancies.

    18. Known hypersensitivity to Gemcitabine or taxanes.

    a. Patients with history of Gemcitabine toxicity in the adjuvant setting requiring more than 1 dose level reduction (as per Dose Modification schema described in Section 8.2.2) are excluded.

    19. Prior treatment with BBI608.

    20. Enrollment on any additional investigational agent study. Enrollment on concurrent observational study is allowed following consultation with the Sponsor.

    21. Patients planning to take a vacation for 7 or more consecutive days during the course of the study.

    Principal Investigator: Tanios Bekaii-Saab, MD

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  • open for enrollment

    Cellular Immunotherapy Treatment Antigen-Directed for EBV Lymphoma

    Protocol: OSU-14109

    Eligibility:

    FOR SCREENING PHASE:

    Inclusion Criteria:

    1. Diagnosis of extranodal NK/T lymphoma, perWHO classification, 4th ed., which must include EBV tumor positivity, measured either by EBV encoded RNA (EBER) or LMP1 immunostaining.

    2. a) Clinically suspected or documented relapse/progression, at any time following at least one cycle of an asparaginase-based chemotherapy OR b) High-risk disease (stage III/IV, KPI groups 3-4 or IPI intermediate-high) at any time (regardless of chemotherapy status and disease relapse/ progression)

    3. Male or female = 18 years of age.

    4. Weigh = 35 kg.

    5. ECOG performance score 0-2, inclusively.

    6. Negative ß-hCG test in women of childbearing potential.

    7. Able to understand and comply with the requirements of the study and to provide written informed consent.

    Exclusion Criteria:

    1. CNS lymphoma.

    2. NK cell leukemia.

    3. Hemophagocytic lymphohistiocytosis.

    4. Positive laboratory test for anti-HIV 1,2; HBsAg, anti-HTLV-I; anti-HCV, or syphilis (Patients with anti-hepatitis B core antibody are eligible if negative for HBsAg).

    5. Use of systemic corticosteroids >0.5 mg/kg/day within 10 days prior to obtaining 100 mL whole blood starting material.

    6. Patient is pregnant or lactating.

    7. Female patient of childbearing potential unwilling to use effective birth control.

    8. Sexually active patients unwilling to utilize one of the more effective birth control methods during the study and for 6 months after the study treatment is concluded. The male partner should use a condom.

    9. Clinically significant medical condition e.g. pulmonary, neurological, cardiovascular, metabolic, that could jeopardize patient safety, interfere with the objectives of the protocol, or limit patient compliance with study requirements, as determined by the Investigator.

    10. Active second malignancy.

    11. Previous non-hematological malignancy, except for adequately treated basal-cell carcinoma of skin or cervical carcinoma in-situ without current evidence of disease, unless the tumor was treated with curative intent more than 5 years prior to study entry.

    12. Any prior allogeneic hematopoietic stem cell or solid organ transplant.

    FOR TREATMENT PHASE:

    Inclusion Criteria:

    1. All Screening Phase inclusion criteria.

    2. Documented relapse or progression following at least one prior cycle of an asparaginase-containing chemotherapy regimen.

    3. At least one prior cycle of gemcitabine-based salvage chemotherapy.

    4. Completed most recent course of chemotherapy at least 2 weeks prior to first study drug dose.

    5. Recovery from acute hematological, hepatic and renal chemotherapy-related toxicities as defined by

    = Grade 1 according to NCI CTCAE v4.0.

    6. Life expectancy = 8 weeks.

    7. Pulse oximetry of = 90% on room air.

    Exclusion Criteria:

    1. All Screening Phase exclusion criteria.

    2. Use of any investigational agents within prior 4 weeks.

    3. Radiotherapy within prior 3 weeks.

    4. Major surgery within prior 2 weeks.

    5. Systemic corticosteroids within 24 hours prior to study drug administration.

    6. Symptoms of cardiac failure with New York Heart Association classification of III or IV.

    7. Clinically significant medical condition e.g. infection, pulmonary, neurological, cardiovascular, metabolic, that could jeopardize patient safety, interfere with the objectives of the protocol, or limit patient compliance with study requirements, as determined by the Investigator.

    Principal Investigator: Pierluigi Porcu, MD, Affiliate

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  • open for enrollment

    A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

    Protocol: OSU-14108

    Eligibility:

    Inclusion Criteria:

    • Patients with histologically/cytologically confirmed advanced solid tumors with FGFR1 or FGFR2 amplification or FGFR3 mutation, for which no further effective standard anticancer treatment exists
    • Patients with advanced/metastatic urothelial cell carcinoma (UCC) with FGFR3 mutations or gene fusions progressing after platinum-based chemotherapy or intolerant to platinum therapy or for whom platinum is contraindicated
    • No more than 2 prior lines of systemic chemotherapy (not including neoadjuvant or adjuvant) for advanced/metastatic disease for UCC patients. UCC patients with more than 2 prior lines of systemic chemotherapy may be considered for inclusion on a case by case basis after discussion with Novartis. Prior immunotherapy or biological therapy is permitted and does not count towards the 2 prior lines.
    • Must be measurable disease for UCC patients
    • A representative tumor sample must be available for molecular testing. The biopsy sample must be obtained from an advanced, invasive or metastatic lesion.
    • Adequate bone marrow function
    • Adequate hepatic and renal function
    • Adequate cardiovascular function

    Contraception:

    • For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen during and for 3 months after the treatment period; must have a negative serum or urine pregnancy test and must not be nursing
    • For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after the treatment period

    Exclusion Criteria:

    • Patients with primary CNS tumor or CNS tumor involvement
    • Patients with history and/or current evidence of endocrine alteration of calcium-phosphate homeostasis
    • History and/or current evidence of ectopic mineralization / calcification including but not limited to the soft tissue, kidneys, intestine, myocard and lung with the exception of calcified lymphnodes and asymptomatic coronary calcification
    • Current evidence of corneal or retinal disorder/ keratopathy incl. but not limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis etc., confirmed by ophthalmologic examination
    • History or current evidence of cardiac arrhythmia and/or conduction abnormality
    • Women who are pregnant or nursing

    Other protocol-defined inclusion/exclusion criteria may apply.

    Principal Investigator: Amir Mortazavi, MD, Affiliate

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  • open for enrollment

    Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery

    Protocol: SWOG-S1310

    Eligibility:

    Inclusion Criteria:

    • DISEASE RELATED CRITERIA
    • Patients must have histologically or cytologically documented carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder with clinical and/or radiologic evidence of unresectable, locally advanced or metastatic disease; patients with ampullary carcinoma are not eligible
    • Patients must have measurable disease; computed tomography (CT) scans or magnetic resonance imaging (MRI)s used to assess measurable disease must have been completed within 28 days prior to registration; CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
    • PRIOR/CONCURRENT THERAPY CRITERIA
    • Patients must have completed any prior chemotherapy at least 21 days prior to registration and have recovered from any of the effects AND
    • Patients must have experienced progression to no more than 1 prior regimen of systemic chemotherapy for advanced biliary cancer OR
    • Patients who received adjuvant chemotherapy and had evidence of disease recurrence within 6 months of completion of the adjuvant treatment are also eligible; if patient received adjuvant treatment and had disease recurrence after 6 months, patients will only be eligible after failing one regimen of systemic chemotherapy used to treat the (unresectable or metastatic) disease recurrence
    • Patients must not have been treated with prior MEK inhibitors; prior 5-FU or capecitabine treatment is allowed only if given as a radiosensitizer concurrently with radiation therapy at least 12 weeks prior to registration or if given as part of any adjuvant therapy regimen >= 12 months prior to study enrollment
    • Patients must have no plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy (including herbal or natural supplements) for treatment of cancer while on this treatment protocol
    • For patients who have received prior cryotherapy, radiation therapy, radiofrequency ablation, therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met:
    • 28 days have elapsed since that therapy (lesions that have not been treated with local therapy must be present and measureable)
    • CLINICAL/LABORATORY CRITERIA
    • Patients must have a Zubrod performance status of 0-1
    • Absolute neutrophil count (ANC) > 1000/mcL
    • Platelets > 100000/mcL
    • Total bilirubin =< 2.0 x the institutional upper limit of normal limits (IULN)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 3 x IULN; if liver metastases are present, AST and ALT must be =< 5 x IULN
    • If the patient has had decompression of the biliary tree within the last 14 days, stability of the bilirubin level needs to be confirmed with two measurements that are within 5 to 7 days of each other; (the second measurement must be obtained within 7 days prior to registration;) both the first and second measurement must be =< 2.0 x IULN; stability is defined as the second measurement being no more than one point higher than the first
    • Patients must have adequate kidney function as evidenced by at least ONE of the following:
    • Serum creatinine =< 1.5 x IULN within 28 days prior to registration
    • Calculated creatinine clearance >= 50 ml/min for patients with creatinine level of 1.0-1.5 x IULN; the serum creatinine value used in the calculation must have been obtained within 28 days prior to registration
    • Patients with known history or current evidence of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) are not eligible:
    • History of RVO or RPED, or predisposing factors to RVO or RPED (e.g. such as uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)
    • Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as:
    • Evidence of new optic disc cupping
    • Evidence of new visual field defects
    • Intraocular pressure > 21 mmHg
    • NOTE: ophthalmic exam is required for all patients; this exam should not be performed until or unless it is very clear the patient is otherwise eligible for registration; this exam should not be performed until or unless it is very clear the patient is otherwise eligible for registration
    • Patients must have echocardiogram and left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (LLN) within 28 days prior to registration; this exam should not be performed until or unless it is very clear the patient is otherwise eligible for registration
    • Patients must not have uncontrolled or clinically significant cardiovascular disease including: myocardial infarction within past 6 months; uncontrolled angina within past 6 months; class II-IV New York Heart Association (NYHA) congestive heart failure; grade 3 cardiac valve dysfunction; cardiac arrhythmia not controlled by medication; history of stroke or transient ischemic attack within 6 months; history of arterial thrombotic event (ATE) of any type in the past 6 months; treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled with anti-hypertensive therapy; known intra-cardiac defibrillators; known cardiac metastases
    • Patients must have an electrocardiogram (ECG) within 28 days prior to registration; patients must have corrected QT interval (QTc) =< 500 msec; this exam should not be performed until or unless it is very clear the patient is otherwise eligible for registration
    • Must be able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
    • Must not have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, or excipients or to dimethyl sulfoxide (DMSO) or other agents used in study
    • Must not have active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible)
    • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
    • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method while on study and for 4 months after discontinuation of study drug; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
    • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
    • SPECIMEN SUBMISSION CRITERIA
    • Patients must submit paraffin-embedded tissue and blood for banking within 28 days after registration; paraffin-embedded tissue from prior surgical resection or from a diagnostic biopsy is acceptable
    • REGULATORY CRITERIA
    • Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
    • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

    Principal Investigator: Tanios Bekaii-Saab, MD

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  • open for enrollment

    TORC1/2 Inhibitor MLN0128 and Bevacizumab in Treating Patients With Recurrent Glioblastoma or Advanced Solid Tumors

    Protocol: OSU-14154

    Eligibility:

    Inclusion Criteria:

    • Patients must have a histologically/cytologically confirmed diagnosis of recurrent glioblastoma or an advanced solid tumor in which bevacizumab has shown benefit in specific disease population and for which standard or curative measures do not exist or are no longer effective
    • Measurable or evaluable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for non-GBM tumors and by Response Assessment in Neuro-Oncology (RANO) criteria for GBM
    • For stage 1 (all patients) and dose expansion (stage 2) endometrial and ovarian cancer cohorts, participants are allowed following unlimited prior therapy; for stage 2 GBM participants, no more than 2 prior relapses are allowed; for these patients, relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy) or a subsequent therapy; the intent therefore is that GBM patients enrolling onto stage 2 had no more than 3 prior therapies (initial and treatment for 2 relapses); if the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered to constitute 1 relapse
    • NOTE: For participants who had prior therapy for a low-grade glioma, the surgical diagnosis of glioblastoma will be considered the first relapse; therefore, these participants may have had more than 3 prior therapies
    • Patients must have recovered from clinically significant toxicity of prior therapy to grade =< 1 or pre-treatment baseline; the following intervals from previous treatments are required prior to day 1 of study therapy:
    • 12 weeks from the completion of radiation for recurrent GBM unless there is surgical diagnosis of recurrence or a new lesion that was not previously radiated
    • 6 weeks from a nitrosourea chemotherapy
    • 3 weeks from a non-nitrosourea chemotherapy
    • 4 weeks from an investigational agent (not Food and Drug Administration [FDA] approved) (or 5 half lives, whichever is shorter)
    • 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.) (or 5 half lives, whichever is shorter)
    • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
    • Absolute neutrophil count >= 1,500/uL
    • Platelets >= 100,000/uL
    • Hemoglobin >= 9.0 g/dL
    • Total bilirubin < 1.5 x institutional upper limit of normal with direct bilirubin within normal limits except for participants with Gilbert's disease
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (=< 5 x upper limit of normal [ULN] if liver metastases are present)
    • Creatinine < 1.5 x normal institutional limits OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine level above institutional normal based either on Cockroft-Gault estimate or based on urine collection (12 or 24 hour)
    • Metabolic: fasting serum glucose (=< 130 mg/dL) and fasting triglycerides =< 300 mg/dL
    • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 6 months after completion of MLN 0128 or bevacizumab administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of MLN0128 or bevacizumab administration
    • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for >= three years prior to registration
    • Solid tumor patients must be off corticosteroids prior to registration; if GBM patient is receiving corticosteroids, patient must be on a stable or decreasing dose of corticosteroids for at least 5 days prior to baseline magnetic resonance imaging (MRI) or computed tomography (CT); if steroids are added or the steroids dose is increased between the date of the screening MRI or CT and the start of treatment, a new baseline MRI or CT is required
    • Patients must be able to swallow whole capsules
    • Ability to understand and the willingness to sign a written informed consent document
    • For stage 2 GBM participants, a block of paraffin embedded tissue or 30 unstained slides at standard 4-5 um thickness from any prior surgery demonstrating GBM pathology must be available for submission
    • Stage 2 endometrial and ovarian cancer patients must have at least one lesion amenable to biopsy; this determination will be made by a member of the interventional radiology team or surgical associate investigator and an associate investigator; this requirement is not necessary for patients in stage 1
    • Solid tumor patients in stage 2 must have a diagnosis of papillary serous, endometrioid or clear cell endometrial carcinoma or, high grade serous, clear cell, endometrioid or mucinous ovarian, fallopian or primary peritoneal carcinoma

    Exclusion Criteria:

    • Concurrent administration of any other investigational agents
    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN0128 or bevacizumab
    • For all stage 2 participants, no prior treatment with mTOR, PI3 kinase or Akt inhibitors; prior treatment with mTOR, PI3 kinase or Akt inhibitors allowed in stage 1 only
    • For stage 2 GBM participants, no prior treatment with bevacizumab/vascular endothelial growth factor receptor (VEGFR) inhibitors; prior treatment with bevacizumab/VEGFR inhibitors is allowed in stage 1 for all participants, as well as stage 2 endometrial and ovarian cancer participants
    • Stage 1 solid tumor and stage 2 endometrial and ovarian cancer participants with known central nervous system (CNS) metastatic lesions which are symptomatic and/or growing; patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll; brain metastasis must be stable for 1 month with verification by imaging (brain MRI completed at screening demonstrating no current evidence of progressive brain metastases); CNS imaging will not be mandated for asymptomatic patients with no history of CNS metastases
    • Concurrent use of enzyme-inducing anti-epileptic drugs (EIAED); patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of MLN0128
    • Subjects taking strong cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2C19 (CYP2C19) inhibitors and/or inducers should be considered with caution; alternative treatments that are less likely to affect MLN0128 metabolism, if available, should be considered; if a subject requires treatment with 1 or more of the strong CYP3A4 and CYP2C19 inhibitors and/or inducers, the principal investigator should be consulted
    • Concurrent use of herbal supplements and other non-traditional medications; all herbal supplements and other non-traditional medications must be stopped before time of registration
    • Concurrent use of anti-coagulants (warfarin, etc.) other than low-molecular weight heparin (LMWH); medication must be stopped before time of registration; if patient has recently been on anti-coagulants other than LMWH, patient must have INR =< 2
    • Evidence of any significant intracranial hemorrhage, as determined by the treating investigator, within 6 weeks from registration or as seen on most recent MRI prior to screening/baseline MRI
    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
    • History of any of the following within 6 months prior to start of MLN0128:
    • Left ventricular ejection fraction (LVEF) =< 55% as determined by multi gated acquisition (MUGA) scan or echocardiogram (ECHO)
    • Heart failure >= New York Heart Association (NYHA) grade 3
    • Significant ST depression of >= 1.5 mm in 2 or more leads and/or T wave inversions in >= 2 leads
    • Complete left bundle branch block
    • Right bundle branch block + left anterior hemiblock (bi-fascicular block)
    • Congenital long QT syndrome
    • QT interval corrected by Fridericia's formula (QTcF) > 450 msec on screening electrocardiogram (ECG)
    • Requirement of inotropic support (excluding digoxin)
    • History or presence of clinically significant ventricular or atrial tachyarrhythmias, or cardiac arrest
    • Clinically significant resting bradycardia
    • Presence of unstable atrial fibrillation (ventricular response > 100 beats per minute)
    • Patients with stable atrial fibrillation are allowed in the study provided they do not meet the other cardiac exclusion criteria
    • History of arrhythmia requiring an implantable cardiac defibrillator
    • Angina pectoris =< 12 months prior to starting drug
    • Acute myocardial infarction =< 12 months prior to starting drug
    • Any valve disease Common Terminology Criteria for Adverse Events (CTCAE) grade
    • Ischemic myocardial event including angina requiring therapy and artery revascularization procedures
    • Placement of a pacemaker for control of rhythm
    • Pulmonary embolism
    • Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures
    • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral MLN0128 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection that requires nutritional support)
    • Use of hematopoietic colony-stimulating growth factors (e.g. filgrastim [G-CSF], sargramostim [GMCSF], lanimostim [M-CSF]) =< 2 weeks prior to starting study drug; erythropoietin, darbepoetin and erythropoietin-biosimilars are allowed for as long as they have been initiated at least 2 weeks prior to study enrollment
    • Pregnant or nursing women; breastfeeding should be discontinued if the mother is treated with MLN0128
    • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; if an HIV-positive patient has adequate cluster of differentiation (CD4) counts (CD4 above the lower limit of institutional normal) and is on antiretroviral therapy with newer agents, which are not strong cytochrome (CYP) inhibitors, they will be eligible
    • Uncontrolled high blood pressure (i.e., systolic blood pressure >= 160 mmHg, diastolic blood pressure >= 90 mmHg)
    • Pulmonary hypertension
    • Uncontrolled asthma or oxygen (O2) saturation < 90% by ABG (arterial blood gas) analysis or pulse oximetry on room air
    • Participants with poorly controlled diabetes mellitus (defined as hemoglobin A1c [HbA1c] > 7%); subjects with a history of transient glucose intolerance due to corticosteroid administration are allowed in this study if all other inclusion/exclusion criteria are met
    • Urine protein should be screened by urinalysis; if protein is 2+ or higher, 24 hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment
    • Serious or non-healing wound, ulcer or bone fracture
    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1
    • Invasive procedures defined as follows:
    • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day 1 therapy
    • Anticipation of need for major surgical procedures during the course of the study
    • Core biopsy within 7 days prior to day 1 therapy
    • Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1
    • Evidence of bleeding diathesis or coagulopathy
    • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

    Principal Investigator: John L Hays, MD, PhD

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  • open for enrollment

    Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Hydrochloride Before Surgery in Treating Patients With Newly Diagnosed Non-Rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

    Protocol: COG-NRGARST1321

    Eligibility:

    Inclusion Criteria:

    • Newly diagnosed and histopathologically confirmed, potentially resectable NRSTS of the extremity and trunk will be eligible for the chemotherapy or non-chemotherapy cohort based on:
    • Evidence of chemotherapy sensitivity of the histologic sarcoma subtype based on existing evidence from prior clinical trials
    • Sufficient risk of metastatic disease to warrant chemotherapy based on size and grade and
    • Medically deemed able or unable to undergo chemotherapy
    • Notes: an incisional biopsy or core biopsy is preferred; fine needle aspiration biopsy is not acceptable to establish the diagnosis
    • ELIGIBLE SITES:
    • Extremities: upper (including shoulder) and lower (including hip)
    • Trunk: body wall
    • INELIGIBLE SITES: Head and neck, visceral organs (with the exception of embryonal sarcoma of the liver), retroperitoneum, peritoneum, pelvis within the confines of the bony pelvis
    • ELIGIBILITY FOR CHEMOTHERAPY COHORT:
    • Stage T2a/b (> 5 cm) and grade 3 AND
    • One of the following chemosensitive histologies as defined in the World Health Organization (WHO) classification of soft tissue tumors (with some evidence of good response to chemoradiation and of sufficient high risk of metastases, or clear evidence of metastases):
    • Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called "undifferentiated soft tissue sarcoma" or "soft tissue sarcoma not otherwise specified [NOS]")
    • Synovial sarcoma
    • Angiosarcoma of soft tissue
    • Adult fibrosarcoma
    • Mesenchymal (extraskeletal) chondrosarcoma
    • Leiomyosarcoma
    • Liposarcoma (excluding myxoid liposarcoma)
    • Undifferentiated pleomorphic sarcoma
    • Embryonal sarcoma of the liver
    • Patients meeting the above criteria (histology, size, and grade) with the EXCEPTION of histologies noted above may enroll on the chemotherapy cohort or the non-chemotherapy cohort at the discretion of the enrolling investigator; patients meeting these criteria with the EXCEPTION of histologies noted above but medically deemed unable to receive chemotherapy or who elect not to receive chemotherapy are eligible for the non-chemotherapy cohort
    • Patients with the following histologies are only eligible for the chemotherapy cohort and cannot enroll on the non-chemotherapy cohort:
    • Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called "undifferentiated soft tissue sarcoma" or "soft tissue sarcoma NOS") in patients < 30 years of age
    • Synovial sarcoma
    • Embryonal sarcoma of the liver
    • ELIGIBILITY FOR NON-CHEMOTHERAPY COHORT:
    • Patients with any size of grade 2 or 3 of the following "intermediate (rarely metastasizing)" or "malignant" tumors, as defined in the WHO classification of soft tissue tumors for which we have consensus data of chemotherapy-resistance are eligible only for the non-chemotherapy cohort:
    • So-called fibrohistiocytic tumors - plexiform fibrohistiocytic tumor, giant cell tumor of soft tissues
    • Fibroblastic/myofibroblastic tumors - solitary fibrous tumor, malignant solitary fibrous tumor, inflammatory myofibroblastic tumor, low grade myofibroblastic sarcoma, myxoinflammatory fibroblastic sarcoma, atypical myxoinflammatory fibroblastic tumor, myxofibrosarcoma, low grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma
    • Tumors of uncertain differentiation - epithelioid sarcoma, alveolar soft part sarcoma, clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma, ossifying fibromyxoid tumor, myoepithelioma, myoepithelial carcinoma, extraskeletal myxoid chondrosarcoma, neoplasms with perivascular epithelioid cell differentiation (PEComa), intimal sarcoma, atypical fibroxanthoma, mixed tumor NOS, phosphaturic mesenchymal tumor, malignant ossifying fibromyxoid tumor, malignant mixed tumor, malignant phosphaturic mesenchymal tumor
    • Chondro-osseous tumors - extraskeletal osteosarcoma
    • Pericytic (perivascular) tumors - malignant glomus tumor
    • Nerve sheath tumors - malignant peripheral nerve sheath tumor, malignant granular cell tumor, epithelioid malignant peripheral nerve sheath tumor, malignant Triton tumor
    • Undifferentiated sarcomas (with a specific pathologic category in the WHO classification) - undifferentiated round cell sarcoma, undifferentiated epithelioid sarcoma, undifferentiated spindle cell sarcoma
    • Patients meeting the criteria (histology, size, and grade) with the EXCEPTION of histologies noted above may enroll on the non-chemotherapy cohort at the discretion of the enrolling investigator; patients meeting these criteria with the EXCEPTION of histologies noted above but medically deemed unable to receive chemotherapy or who elect not to receive chemotherapy are eligible for the non-chemotherapy cohort; Note that tumors arising in bone are NOT eligible for this study
    • Extent of disease:
    • Patients with non-metastatic and metastatic disease are eligible
    • Initially unresectable patients, with or without metastatic disease, are eligible as long as there is a commitment at enrollment to resect the primary tumor
    • Sufficient tissue and blood must be available to submit for required biology studies
    • Lansky performance status score >= 70 for patients =< 16 years of age
    • Karnofsky performance status score >= 70 for patients > 16 years of age
    • Absolute neutrophil count >= 1500/uL; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
    • Platelet count >= 100,000/uL; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
    • Hemoglobin >= 8 g/dL for patients =< 16 years of age; >= 9 g/dL for patients > 16 years of age; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
    • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or normal serum creatinine based on age/gender as follows:
    • 2 to < 6 years; 0.8 mg/dL male; 0.8 mg/dL female
    • 6 to < 10 years; 1 mg/dL male; 1 mg/dL female
    • 10 to < 13 years; 1.2 mg/dL male; 1.2 mg/dL female
    • 13 to < 16 years; 1.5 mg/dL male; 1.4 mg/dL female
    • >= 16 years; 1.5 mg/dL male; 1.4 mg/dL female
    • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
    • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate transaminase [AST]) or serum glutamate pyruvate transaminase [SGPT] (alanine transaminase [ALT]) < 2.5 x upper limit of normal (ULN) for age
    • Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by radionuclide angiogram
    • Corrected QT interval (QTc) < 480 msec
    • No evidence of dyspnea at rest, no exercise intolerance, and a resting pulse oximetry reading > 94% on room air if there is clinical indication for determination
    • Patients on low molecular weight heparin or Coumadin (with a stable international normalized ratio [INR]) are eligible
    • Patient must have a life expectancy of at least 3 months with appropriate therapy
    • All patients and/or their parents or legal guardians must sign a written informed consent
    • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

    Exclusion Criteria:

    • Patients with grade 1 NRSTS tumors of any size are not eligible
    • Patients with known central nervous system (CNS) metastases are not eligible; Note: brain imaging is not an eligibility requirement
    • Patients with evidence of active bleeding or bleeding diathesis will be excluded (Note: patients aged > 17 years with excess of 2.5 mL of hemoptysis are not eligible)
    • Patients with gross total resection of the primary tumor prior to enrollment on ARST1321 are NOT eligible; patients who have experienced tumor recurrence after a gross total tumor resection are NOT eligible
    • Patients with uncontrolled hypertension are ineligible; uncontrolled hypertension is defined as follows:
    • Patients aged =< 17 years: greater than 95th percentile systolic and diastolic blood pressure based on age and height which is not controlled by one anti-hypertensive medication
    • Patients aged > 17 years: systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg that is not controlled by one anti-hypertensive medication
    • Prior Therapy:
    • Patients must have had no prior anthracycline (eg, doxorubicin, daunorubicin) or ifosfamide chemotherapy
    • Patients must have had no prior use of pazopanib or similar multi-targeted tyrosine kinase inhibitors (TKI)
    • Patients must have had no prior radiotherapy to tumor-involved sites
    • Note: patients previously treated for a non-NRSTS cancer are eligible provided they meet the prior therapy requirements; patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded
    • Other types of invasive malignancy that are not disease free within 3 years except for non-melanoma skin cancer, lentigo maligna, any carcinoma-in-situ or prostate cancer with low risk factors
    • CYTOCHROME P450 3A4 (CYP3A4) substrates WITH narrow therapeutic indices: patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices within 7 days prior to study enrollment, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; Note: the use of fentanyl is permitted
    • CYP3A4 Inhibitors: patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to itraconazole, clarithromycin, erythromycin many non-nucleoside reverse-transcriptase inhibitors (NNRTIs), diltiazem, verapamil, and grapefruit juice are not eligible
    • CYP3A4 Inducers: patients chronically receiving drugs that are known potent CYP3A4 inducers within 14 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort are not eligible (with the exception of glucocorticoids)
    • Certain medications that are associated with a risk for QTc prolongation and/or Torsades de Pointes, although not prohibited, should be avoided or replaced with medications that do not carry these risks, if possible
    • Subjects with any condition that may impair the ability to swallow or absorb oral medications/investigational product including:
    • Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow capsules or pills
    • Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
    • Active peptic ulcer disease
    • Malabsorption syndrome
    • Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:
    • Active peptic ulcer disease
    • Known intraluminal metastatic lesions
    • Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
    • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment
    • Subjects with any of the following cardiovascular conditions within the past 6 months
    • Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
    • Cardiac arrhythmia
    • Admission for unstable angina
    • Cardiac angioplasty or stenting
    • Coronary artery bypass graft surgery
    • Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks
    • Arterial thrombosis
    • Symptomatic peripheral vascular disease
    • Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; a subject who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible
    • History of serious or non-healing wound, ulcer, or bone fracture
    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
    • Patients who are unable to swallow whole tablets are not eligible
    • Patients with a body surface area < 0.5 m^2 are not be eligible
    • Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible
    • Patients who are receiving any other investigational agent(s)
    • Pregnancy and breast feeding:
    • Female patients who are pregnant are ineligible
    • Lactating females are not eligible unless they have agreed not to breastfeed their infants during treatment and for a period of 1 month following completion of treatment
    • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
    • Unwillingness to use an effective contraceptive method for the duration of their study participation and for at least 1 month after treatment is completed if sexually active with reproductive potential
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  • open for enrollment

    Selinexor in Treating Patients With Relapsed Small Cell Lung Cancer

    Protocol: OSU-14136

    Eligibility:

    Inclusion Criteria:

    • Written informed consent in accordance with federal, local, and institutional guidelines
    • Patients should have estimated life expectancy of > 3 months at study entry
    • Patients with relapsed small cell lung cancer - diagnosis must be histologically confirmed
    • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at the time of study entry
    • Objective evidence of disease progression on study entry
    • Prior systemic anticancer therapy: patients will have received no more than 2 prior chemotherapy regimens; the regimen(s) may have included biological, molecularly targeted or immune therapies; patients with primary refractory disease (i.e., those patients with progressive disease on first line chemotherapy) and patients with disease relapse within 90 days of completion of initial chemotherapy (chemotherapy resistant) are excluded; patients with limited stage small cell lung cancer (SCLC) and systemic relapse who are not felt to be candidates for repeat platinum-based chemotherapy at relapse are eligible for enrollment
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
    • Absolute neutrophil count (ANC) > 1000/mm^3
    • Platelet count > 75,000 mm^3
    • Total bilirubin < 2 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3 times ULN)
    • Alanine aminotransferase (ALT) < 2.5 times ULN; in the case of known (radiological and/or biopsy documented) liver metastasis, ALT < 5.0 times ULN is acceptable
    • Albumin >= 3.0 mg/dl
    • Estimated creatinine clearance of >= 30 mL/min, calculated using the formula of Cockroft and Gault
    • Amylase =< 1.5 x ULN
    • Lipase =< 1.5 x ULN
    • Alkaline phosphatase limit =< 2.5 x ULN
    • Female patients of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening; male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose
    • Resolution to grade =< 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v4.03) of all clinically significant toxic effects of prior anti-cancer therapy (with the exception neuropathy, which may be =< grade 2 within 14 days prior to cycle 1 day 1)
    • Available archival tumor tissue or willingness to undergo repeat biopsy is required at trial initiation

    Exclusion Criteria:

    • Primary refractory disease (progressive disease on initial platinum based chemotherapy) or chemotherapy-resistant disease (disease progression within 90 days of completion of initial chemotherapy)
    • Patients who are pregnant or lactating
    • Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =< 2 weeks prior to cycle 1 day 1; any clinical trial therapy (including investigational anti-cancer study) =< 3 weeks prior to cycle 1 day 1
    • Prior treatment with selinexor
    • Major surgery within 3 weeks before day 1
    • Unstable cardiovascular function:
    • Electrocardiogram (ECG) abnormalities requiring treatment, or
    • Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3
    • Myocardial infarction (MI) within 3 months
    • Symptomatic ischemia or angina
    • Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
    • Known to be human immunodeficiency virus (HIV) seropositive
    • Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) RNA or hepatitis B surface antigen (HBsAg) (hepatitis B virus [HBV] surface antigen)
    • Serious psychiatric or medical conditions that could interfere with treatment
    • History of seizures, movement disorders or cerebrovascular accident within the past 5 years prior to cycle 1 day 1
    • Concurrent therapy with approved or investigational anticancer therapeutic other than steroids
    • Patients with > 3 liver metastases at time of enrollment
    • Patients with coagulation problems and active bleeding in the last month (peptic ulcer, epistaxis, spontaneous bleeding)
    • Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications
    • Patients who are severely underweight (body mass index [BMI] less than 17) or patients with a body surface area (BSA) < 1.4 m^2 as calculated per Dubois 1916 or Mosteller 1987
    • Uncontrolled brain metastases or leptomeningeal involvement; patients with brain metastases are permitted if they have received appropriate therapy and demonstrated control of the brain metastases or leptomeningeal disease following therapy; patients with known brain metastases will require magnetic resonance imaging (MRI) brain to demonstrate disease control prior to enrollment (lack of symptom progression for two weeks off therapeutic doses of steroids, excluding chronic steroids used for control of chronic obstructive pulmonary disease [COPD])
    • Prior cancer diagnosis is allowed if patient is disease-free for >= 3 years, or disease free for < 3 years for treated basal cell/ squamous cell skin cancer or in situ cervical cancer
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  • open for enrollment

    Ibrutinib and Palbociclib Isethionate in Treating Patients With Previously Treated Mantle Cell Lymphoma

    Protocol: OSU-14148

    Eligibility:

    Inclusion Criteria:

    • Patients must have histologically or cytologically confirmed mantle cell lymphoma as defined by the World Health Organization; all patients must have either t(11;14) by karyotype or fluorescent in-situ hybridization (FISH) or positive immunohistochemistry for cyclin D1
    • Subjects must have measureable disease defined as at least one tumor lesion of at least 1.5 cm or a peripheral blood cluster of differentiation (CD)5+, CD19+ lymphocyte count of at least 5,000 cells/uL
    • Subjects must have received at least one prior treatment regimen
    • Subjects that have received prior ibrutinib or PD 0332991 (palbociclib) are ineligible
    • Subjects that have undergone prior allogeneic stem cell transplantation will only be eligible if the transplant occurred at least 1 year prior to study entry, the patient is no longer taking any immunosuppressive therapy, and there are no significant ongoing transplant-related adverse effects
    • Subjects who have had chemotherapy, radiotherapy, antibodies, or investigational agents within 4 weeks prior to entering the study unless progression has been documented while on treatment and all treatment-related toxicities have resolved to pre-treatment baseline; subjects may be receiving equivalent to prednisone at a maximum dose of 20 mg/day orally
    • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
    • Absolute neutrophil count (ANC) >= 750 cells/uL
    • Platelets >= 50,000 cells/uL
    • Total bilirubin =< 1.5 times upper limit of normal unless due to Gilbert's disease
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times upper limit of normal
    • Calculated creatinine clearance >= 60 mL/min by Cockcroft-Gault
    • Corrected QT interval (QTc) =< 480 ms
    • Subjects with known or suspected central nervous system (CNS) involvement are not eligible
    • Subjects with serologic status reflecting active viral hepatitis B or C infection are not eligible; subjects that are hepatitis B core antibody positive but antigen negative will need negative polymerase chain reaction (PCR) prior to enrollment; hepatitis B antigen or PCR-positive patients will be excluded
    • Subjects with uncontrolled human immunodeficiency virus (HIV) are not eligible; controlled HIV is defined as a CD4 count > institutional lower limit of normal and no current co-infection; uncontrolled HIV is all other HIV infection; note that patients with controlled infection should be allowed to participate only if they are not receiving prohibited cytochrome P450 (CYP) interactive medications
    • Subjects unable to swallow capsules or with disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption, such as malabsorption syndrome, resection of small bowel, or poorly controlled inflammatory bowel disease affecting the small intestine are not eligible
    • Subjects with uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible
    • Subjects with uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in declining platelet or hemoglobin levels within the 4 weeks prior to first dose of study drug are not eligible
    • Patients with transfusion-dependent thrombocytopenia are not eligible
    • Subjects with myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities are not eligible; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
    • Subjects with a history of stroke or intracranial hemorrhage within 6 months prior to enrollment are not eligible
    • Subjects with a history of malignancy are not eligible with the exception of the following:
    • Malignancy treated within curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
    • Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
    • Adequately treated cervical carcinoma in situ without current evidence of disease
    • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ibrutinib administration; subjects should be offered the opportunity to bank sperm or eggs prior to initiation of study drug
    • Female subjects that are pregnant or breastfeeding are not eligible
    • Subjects that have received anticoagulation therapy with warfarin or equivalent vitamin K antagonists within the last 28 days are not eligible
    • Subjects with a bleeding diathesis are not eligible
    • Subjects receiving other investigational agents are not eligible
    • Subjects should be willing to undergo a research related biopsy prior to treatment and at the time of progression
    • Subjects must give informed consent and must be willing and able to comply with the scheduled visits, treatment plans, laboratory tests, and other procedures

    Principal Investigator: Kristie A Blum, MD, Affiliate

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