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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

    Methods Project 4: Clinical Trial

    Protocol: OSU-14104

    Eligibility:

    Inclusion Criteria: - Male or female subjects who are at least 18 years of age; - Daily smoker; - Generally good health; - Subject has provided written informed consent to participate in the study (adolescents under the age of 18 will be excluded because this project involves continued use of tobacco products and new tobacco products); Exclusion Criteria: - Unstable health - Pregnant or breastfeeding (due to toxic effects from tobacco products). - Unable to read for comprehension or completion of study documents.

    Principal Investigator: Peter Shields, MD

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  • open for enrollment

    A Blanket Protocol to Study Oral Regorafenib in Patients With Refractory Liposarcoma, Osteogenic Sarcoma, and Ewing/Ewing-like Sarcomas

    Protocol: OSU-14056

    Eligibility:

    Inclusion Criteria:

    • Patients must have histologically or cytologically confirmed advanced/metastatic liposarcoma, osteogenic sarcoma, or Ewing/Ewing-like sarcoma of soft tissue or bone. This study will accept the diagnosis made at the investigator's center.
    • WHO Performance Status 0, 1 or 2. A maximum of 1/3 of patients in cohorts A & B may be WHO performance status 2.
    • At least one prior line of systemic therapy for the sarcoma diagnosis (neoadjuvant, adjuvant or metastatic disease).
    • All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v 4.0 Grade 1 or less (except alopecia) at the time of signing the Informed Consent Form (ICF).
    • Subject must be able to swallow and retain oral medication.
    • At least one site of measurable disease on x-ray/CT/MRI scan as defined by RECIST 1.1. Baseline imaging must be performed within 28 days of Day 1 of study.
    • Adequate organ function within 14 days of registration INR (International Normalized Ratio) : patients with no prior evidence of underlying abnormality in coagulation parameters exists, according to the written documentation of the treating physician
    • Evidence of progression of disease as defined by RECIST 1.1 (i.e. new disease sites or 30% growth of index lesions) within 6 months of registration
    • Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS (central nervous system) metastatic disease and are without evidence of clinical progression for at least 12 weeks after therapy.

    Exclusion Criteria:

    • Patients with documentation of well differentiated liposarcoma only (of the well differentiated/dedifferentiated liposarcoma family) are specifically excluded, owing to its characteristically slow growth. If high grade areas are suspected (dedifferentiation), but not proved by pathology analysis (e.g. after primary resection of a well-differentiated liposarcoma), a biopsy must be performed to demonstrate the high-grade dedifferentiated disease.
    • Prior systemic therapy with a small molecule oral kinase inhibitor, including but not limited to: pazopanib, sunitinib, sorafenib, everolimus, sirolimus, vemurafenib, dasatinib.
    • Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study. Patients who progress on placebo are specifically allowed to enroll on the treatment arm of the study if they meet all other entry criteria.
    • Concurrent, clinically significant, active malignancies within 12 months of study enrollment
    • Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.
    • Major surgery within 28 days prior to study registration or those patients who have not recovered adequately from prior surgery
    • Patients who have received wide field radiotherapy ≤ 28 days (defined as > 50% of volume of pelvis bones or equivalent) or limited field radiation for palliation < 14 days prior to study registration or those patients who have not recovered adequately from side effects of such therapy.
    • Patients who have received prior systemic therapy < 14 days prior to study registration or have not recovered adequately from toxicities to CTCAE v. 4.0 grade 1 or less; prior investigational therapy may not have been given < 5 half-lives of last dose of treatment, or < 14 days, whichever is greater.
    • Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v 4.0] on repeated measurement) despite optimal medical management.
    • Active or clinically significant cardiac disease including: Congestive heart failure-New York Heart Association (NYHA) > class II, Active coronary artery disease, Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, Unstable angina (anginal symptoms at rest), new onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization3.2.11
    • Evidence or history of bleeding diathesis or coagulopathy
    • Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to study registration
    • Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment
    • Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.
    • Ongoing infection > Grade 2 NCI-CTCAE v 4.0
    • Presence of a non-healing wound, non-healing ulcer, or benign bone fracture (patients with stress insufficiency fractures e.g. from osteoporosis or pathological fracture from tumor are eligible for study)
    • Patients with seizure disorder requiring medication
    • Persistent proteinuria: Grade 3 NCI-CTCAE v 4.0 (> 3.5 g/24 h, measured by urine protein:creatinine ratio on a random urine sample)
    • Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
    • Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE version 4.0 Grade 2 dyspnea)
    • History of organ allograft (including corneal transplant).
    • Known or suspected allergy or hypersensitivity to regorafenib, or excipients of the formulations given during the course of this trial.
    • Any malabsorption condition.
    • Women who are pregnant or breast-feeding.
    • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
    • Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
    • Inability to comply with protocol required procedures.
    • Use of any herbal remedy (e.g. St. John wort [Hypericum perforatum]).
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  • open for enrollment

    Ponatinib Hydrochloride in Treating Patients With Refractory Metastatic Cancers and Genetic Alterations

    Protocol: OSU-14078

    Eligibility:

    Inclusion Criteria:

    • Patients with histologically or cytologically confirmed diagnosis of refractory metastatic solid tumor or chronic hematological malignancy who are eligible for investigational drug therapy
    • Patients must have tumor suitable for biopsy (as assessed by trained specialists in interventional radiology) and medically fit to undergo a biopsy or surgical procedure OR if patients do not have a tumor suitable for biopsy but have another tissue available for molecular evaluation
    • Patients should have activating genomic alterations in FGFR (mutations, fusions or amplifications [> 6 copies]) or activating genomic alterations in KIT, platelet-derived growth factor receptor alpha [PDGFRα], ret proto-oncogene [RET], ABL proto-oncogene 1, non-receptor tyrosine kinase [ABL1] and fms-related tyrosine kinase 3 [FLT3] by any validated Clinical Laboratory Improvement Amendments [CLIA]-certified molecular testing (fluorescent in situ hybridization [FISH], polymerase chain reaction [PCR] or sequencing data are acceptable); CLIA validated results from other institutions; diagnostic labs (e.g. foundation medicine) are acceptable; additional types of activating alterations in these genes can be approved by the principal investigator (PI)
    • Patients with advanced cancers should have had at least one prior therapy that is considered standard for that disease type
    • Patients with solid tumors must have measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
    • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 80%)
    • Life expectancy of greater than 3 months
    • Patients with multiple malignancies remain eligible
    • Patients with an inherited cancer syndrome or a medical history suggestive of an inherited cancer syndrome remain eligible
    • Patients must have controlled blood pressure with a systolic blood pressure < 140 mmHg and diastolic < 90 mmHg; anti-hypertensive medications are permitted
    • 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 through 4 months after the end of treatment; for females of childbearing potential, a negative pregnancy test must be documented prior to randomization
    • Absolute neutrophil count >= 1,500/mcL
    • Platelets >= 75,000/mcL
    • Total bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome (< 5 if liver involvement with primary tumor)
    • Serum lipase and amylase =< 1.5 x ULN
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
    • Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal by echocardiogram (ECHO) or multi gated acquisition (MUGA)
    • Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min
    • Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:

    • Patients with acute hematological malignancies (e.g. acute myeloid leukemia)
    • Major surgery (e.g. thoracic, abdominal, vascular, neurosurgery) within 28 days prior to initiating therapy
    • History of acute pancreatitis within one year of study or history of chronic pancreatitis
    • History of alcohol abuse
    • Have uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)
    • Patients who are receiving any other investigational therapeutic agents
    • Patients with gastrointestinal stromal tumor (GIST)
    • Patients with history of clinically significant bleeding disorder
    • Patients with chronic myelocytic or myelogenous leukemia (CML)
    • Patients with multiple myeloma and t(4; 14) translocation with aberrant expression of wild type FGFR3 by immunoglobulin (IgH) promoter (conversely, patients with t (4; 14) translocation and FGFR3 mutation remain eligible)
    • Pregnant women are excluded from this study; breastfeeding should be discontinued
    • Patients who are incarcerated are not eligible
    • Patients with any history of arterial thromboembolic disease; any patient with a history of myocardial infarction (MI), stroke, transient ischemic attack (TIA), unstable angina or peripheral vascular disease will not be eligible
    • Patients with history of recurrent venous thromboembolism (deep venous thrombosis or pulmonary embolism) or history of venous thromboembolism within 6 months will not be eligible
    • Patients with history of active hepatitis B or C infection or chronic hepatitis with Child Pugh B or C hepatic dysfunction
    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ponatinib
    • Patients with history of atrial arrhythmia (requiring any anti-arrhythmic therapy) or patients with any history of ventricular arrhythmia are excluded
    • Clinically significant, uncontrolled intercurrent illness including, but not limited to:
    • Symptomatic or active infection
    • Uncontrolled hypertension (diastolic blood pressure > 90 mm Hg; systolic > 140 mm Hg); patients with hypertension should be under treatment on study entry to effect blood pressure control
    • Psychiatric illness/social situations that would limit compliance with study requirements
    • Patients with history of congestive heart failure or LVEF less than lower limit of normal per local institutional standards are excluded
    • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
    • Patients on medications known to be associated with Torsades de Pointes
    • 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
    • Patients taking medications or herbal supplements that are known to be strong cytochrome P450 3A4 (CYP3A4) inhibitors within at least 14 days before the first dose of ponatinib are excluded
    • Patients with symptomatic or progressive brain metastases are ineligible; subjects with treated brain metastases are eligible if they have no radiographic or other signs of progression in the brain for >= 4 weeks after completion of local therapy
    • Patients who have received prior FGFR targeted therapy

    Principal Investigator: Sameek Roychowdhury, MD, PhD

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  • open for enrollment

    INHERIT EGFR - Studying Germline EGFR Mutations

    Protocol: OSU-14072

    Eligibility:

    Inclusion Criteria:

    • Diagnosis of cancer of any type with an EGFR T790M mutation identified on genotyping of cancer; or
    • Have a first- or second-degree relative known to carry a germline EGFR mutation; or
    • Have a known germline EGFR mutation

    Exclusion Criteria:

    • Subjects with lung cancer and an acquired T790M mutation first detected after exposure to an EGFR tyrosine kinase inhibitor such as erlotinib or gefitinib
    • Too ill to complete the study questionnaire or provide the necessary specimen for testing
    • Unable to give informed consent
    • Unable to speak or read English
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  • open for enrollment

    Avelumab in Metastatic or Locally Advanced Solid Tumors (JAVELIN Solid Tumor)

    Protocol: OSU-13257

    Eligibility:

    Inclusion Criteria for dose escalation and expansion phase:

    • Signed written informed consent
    • Male or female subjects aged greater than or equal to 18 years
    • Subjects must have histologically or cytologically proven metastatic or locally advanced solid tumors, for which no standard therapy exists or standard therapy has failed. Availability of tumor archival material or fresh biopsies is optional for subjects in dose escalation
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry and an estimated life expectancy of at least 3 months
    • Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST 1.1, except for subjects with metastatic castrate-resistant prostate cancer (mCRPC) or metastatic breast cancer (MBC) who may be enrolled with objective evidence of disease without a measureable lesion
    • Adequate hematological, hepatic and renal function as defined in the protocol
    • Effective contraception for both male and female subjects if the risk of conception exists
    • Other protocol defined inclusion criteria could apply

    Inclusion Criteria for expansion phase:

    • Subjects must have relapsed, refractory, or progressive disease following last line of treatment (with the exception of the gastric and gastroesophageal junction (GEJ) cancer cohort, which does not require progression). Availability of tumor archival material or fresh biopsies (excluding bone biopsies) is mandatory for eligibility in the expansion cohorts. For subjects in the MBC cohort, the biopsy or surgical specimen must have been collected within 90 days prior to the first investigational medicinal product (IMP) administration. Specifically, the following will be required:
    • NSCLC post platinum doublet: Histologically or cytologically confirmed stage IIIB or stage IV NSCLC that has progressed after 1 line of platinum-containing doublet chemotherapy. Subjects should have received only 1 line of platinum-containing treatment for metastatic disease (i.e., adjuvant treatment with a platinum-containing regimen is not sufficient for eligibility because not received in the context of a metastatic disease). Subjects in the NSCLC cohort will only be enrolled in USA
    • NSCLC first line: Stage IV (per 7th International Association for the Study of Lung Cancer [IASLC] classification) or recurrent NSCLC that is histologically proven. Subjects must not have received treatment for their metastatic or recurrent disease. No activating epidermal growth factor receptor (EGFR) mutation nor ALK translocation/re-arrangement
    • Gastric and GEJ cancer: Histologically confirmed, unresectable locally advanced or metastatic adenocarcinoma of the gastric and gastro-esophageal junction, treated with first-line chemotherapy combination with or without disease progression. Subjects should have received no more than 1 line of treatment for metastatic disease. Subjects should not have been treated with trastuzumab (but can be Human Epidermal growth factor Receptor 2 [HER2] positive). Subjects who received any platinum containing doublet or triplet as a neoadjuvant chemotherapy strategy, but are not ultimately candidates for surgery will also be eligible, as long as they did not have progressive disease after completion of the neoadjuvant chemotherapy. In addition, subjects with gastric cancer can enter in the study if their white blood cell (WBC) and lymphocyte count is as defined in the protocol
    • MBC: Subjects must have histologically confirmed locally advanced or MBC and have tumor that is refractory to or progressive after standard of care therapy. Subjects must have received no more than 3 prior lines of cytotoxic therapy for metastatic disease. Subjects must have received a taxane and an anthracycline, unless contra-indicated
    • Secondary expansion cohorts: Metastatic colorectal cancer (mCRC), Metastatic castrate-resistant prostate cancer (mCRPC), melanoma, ovarian cancer, ACC, mesothelioma, urothelial carcinoma and renal cell carcinoma as defined in the protocol
    • Efficacy expansion cohorts: Gastric and GEJ cancer (third line), ovarian cancer (platinum Refractory + liposomal doxorubicin), urothelial carcinoma, and HNSCC as defined in the protocol
    • Other protocol defined inclusion criteria for expansion phase could apply

    Exclusion Criteria for dose escalation and expansion phase:

    • Concurrent treatment with a non-permitted drug
    • Prior therapy with specific antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
    • Concurrent anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of trial treatment; or concurrent systemic therapy with immunosuppressive agents, use of hormonal agents within 7 days before the start of trial treatment as defined in the protocol. Note: Subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab.
    • Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
    • Rapidly progressive disease (for example, tumor lysis syndrome)
    • Active or history of central nervous system metastases
    • Receipt of any organ transplantation including allogeneic stem-cell transplantation
    • Significant acute or chronic infections as defined in the protocol
    • Active or history of any autoimmune disease (subjects with diabetes Type 1, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies
    • Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma
    • Persisting toxicity related to prior therapy greater than Grade 1 NCI-CTCAE v4.0, however sensory neuropathy less than or equal to Grade 2 is acceptable
    • Pregnancy or lactation period
    • Known alcohol or drug abuse
    • Clinically significant (that is, active) cardiovascular disease
    • All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the investigator, might impair the subject's tolerance of trial treatment
    • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
    • Legal incapacity or limited legal capacity
    • Non-oncology vaccine therapies for prevention of infection disease (for example, seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of study drug administration. Vaccination while on study is also prohibited except for administration of the inactivated influenza vaccine

    Principal Investigator: John L Hays, MD, PhD

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  • open for enrollment

    A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors

    Protocol: OSU-11024

    Eligibility:

    Inclusion Criteria:

    • Has provided signed written informed consent for this study
    • Has demonstrated compliance with study drug(s), treatment visit schedules, and the requirements and restrictions listed in the consent form
    • Is currently participating in a GSK-sponsored study of GSK2118436
    • Currently has no evidence of progressive disease, as determined by the investigator, following previous treatment with GSK2118436 (either as monotherapy or as part of a combination treatment regimen)
    • For Cohort C only: Subjects must have a calcium phosphate product (CPP) of <4.4 mmol^2/L^2 (55 mg^2/dL^2) if they are to continue treatment with GSK1120212
    • Continued ability to swallow and retain orally administered study drug(s) and does not have any clinically significant GI abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
    • Women of childbearing potential and men with reproductive potential must be willing to continue practicing acceptable methods of birth control during the study NOTE: Oral contraceptives are not reliable due to potential drug-drug interaction with GSK2118436
    • Women of childbearing potential must have a negative serum pregnancy test at the time of transition to this study and before the first dose of study treatment
    • French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category

    Exclusion Criteria:

    • Permanent discontinuation of GSK2118436 in the parent study due to toxicity or disease progression
    • Local access to commercially available GSK2118436
    • Currently receiving treatment with any prohibited medication(s)
    • Any unresolved toxicity > Grade 2 (National Cancer Institute-Common Toxicity Criteria for Adverse Events [NCI-CTCAE], version 4.0) from parent study treatment, except for alopecia, will need to be approved by the GSK Medical Monitor
    • Uncontrolled diabetes, hypertension or other medical conditions at the time of transition to this study that may interfere with assessment of toxicity
    • Presence of rheumatoid arthritis
    • Corrected QT (QTc) interval >/= 480 msec at the time of transition to this study
    • Left ventricular ejection fraction (LVEF) </= institutional lower limit of normal (LLN) by ECHO at the time of transition to this study
    • Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system at the time of transition to this study
    • Pregnant or lactating female
    • Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions at the time of transition to this study that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator or GSK Medical Monitor
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  • open for enrollment

    Cabozantinib-S-Malate in Treating Patients With Advanced Solid Tumors and Human Immunodeficiency Virus

    Protocol: AMC-087

    Eligibility:

    Inclusion Criteria:

    • Patients must have known HIV infection and histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; any number of prior cancer therapies will be permitted; at least 4 weeks must have elapsed since prior chemotherapy or biological therapy, 6 weeks if the regimen included carmustine (BCNU) or mitomycin C; prior radiation therapy to the thoracic cavity, abdomen, or pelvis must be completed at least 3 months prior to registration; radiotherapy to any other site (including bone or brain metastases) must be completed at least 28 days prior to registration
    • Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immuno sorbent assay (ELISA), positive western blot, or any other federally approved licensed HIV test; alternatively, this documentation may include a record that another physician has documented that the participant has HIV infection based on prior ELISA and western blot, or other approved diagnostic tests
    • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
    • Life expectancy of greater than 12 weeks
    • Leukocytes >= 3,000/mcL
    • Absolute neutrophil count >= 1,500/mcL
    • Platelets >= 100,000/mcL
    • Total bilirubin=< 1.5 × upper limit of normal (ULN) (for subjects with Gilbert's disease or with atazanavir- or indinavir-induced unconjugated hyperbilirubinemia [without aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation], =< 3 × ULN)
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 × institutional upper limit of normal
    • Creatinine =< 1.5 × ULN
    • Creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
    • Hemoglobin >= 9 g/dL
    • Serum albumin >= 2.8 g/dL
    • Lipase < 2.0 × ULN and no radiologic or clinical evidence of pancreatitis
    • Urine protein/creatinine ratio (UPCR) =< 1
    • Serum phosphorus >= lower limit of normal (LLN)
    • Calcium >= LLN
    • Magnesium >= LLN
    • Potassium >= LLN
    • A cluster of differentiation (CD)4+ lymphocyte count > 50/mcL will be required within 2 weeks of study participation
    • Women of childbearing potential must have a negative pregnancy test at screening; women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal; postmenopause is defined as amenorrhea >= 12 consecutive months; note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
    • Women of child-bearing potential and men must agree to use adequate contraception 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 6 months after completion of cabozantinib administration; sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 6 months after the last dose of study drug(s), even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 6 months after the last dose of study drug
    • Participating patients MUST receive appropriate care and treatment for HIV infection, including antiretroviral medications, when clinically indicated and should be under the care of a physician experienced in HIV management; patients will be eligible regardless of antiretroviral medication (including no antiretroviral medication) provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 8 weeks following study entry; as study-specific (antiretroviral-based) strata fill, however, only patients who are receiving the therapies eligible for the remaining open strata will be accrued
    • Ability to understand and the willingness to sign a written informed consent document
    • Subjects must in the opinion of the investigator be capable of complying with this protocol

    Exclusion Criteria:

    • Prior treatment with cabozantinib (XL184)
    • The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
    • The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 4 weeks or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment; note: Subjects with prostate cancer currently receiving luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists may be maintained on these agents
    • The subject has received any other type of investigational agent within 28 days before the first dose of study treatment
    • The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
    • The subject has a primary brain tumor
    • The subject has active brain metastases or epidural disease; subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 4 weeks before starting study treatment are eligible; subjects with treated brain metastasis should not take enzyme-inducing anticonvulsive therapies (EIACDs) within 2 weeks of registration, though non-enzyme inducing anticonvulsive drugs such as levetiracetam are allowed; neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment; baseline brain imaging with contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scans for subjects with known brain metastases is required to confirm eligibility
    • The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test >= 1.3 x the laboratory ULN within 7 days before the first dose of study treatment
    • The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor xabans (Xa) inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted
    • The subject requires chronic concomitant treatment with the following strong cytochrome P450 3A4 (CYP3A4) inducers OTHER than antiretroviral agents: dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, primidone, modafinil, and other enzyme inducing anti-convulsant drugs (EIACD), and St. John's Wort; use of efavirenz or etravirine is permitted for patients considered for the CYP3A4-inducer based antiretroviral therapy (ART) regimen arm (Stratum B) of the trial
    • The subject requires concomitant treatment with the following inhibitors of CYP3A4:
    • Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin
    • Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole, posaconazole
    • Antidepressants: nefazodone
    • Antidiuretic: conivaptan
    • Gastrointestinal (GI): cimetidine, aprepitant
    • Hepatitis C: boceprevir, telaprevir
    • Miscellaneous: Seville oranges, grapefruit, or grapefruit juice and/or pummelos, star fruit, exotic citrus fruits, or grapefruit hybrids); use of any of anti-retrovirals (delavirdine) or protease inhibitors (ritonavir, indinavir, lopinavir/ritonavir, saquinavir, nelfinavir) is permitted; specifically, ritonavir and cobicistat is permitted for patients considered for the CYP3A4-inhibitor based ART regimen arm (Stratum A) of the trial
    • The subject has experienced any of the following:
    • Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
    • Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment
    • Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
    • The subject has radiographic evidence of cavitating pulmonary lesion(s)
    • The subject has tumor in contact with, invading or encasing any major blood vessels
    • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
    • Cardiovascular disorders including:
    • Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening
    • Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mmHg systolic, or > 90 mmHg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
    • Any history of congenital long QT syndrome
    • Any of the following within 6 months before the first dose of study treatment:
    • Unstable angina pectoris
    • Clinically-significant cardiac arrhythmias
    • Stroke (including transient ischemic attack [TIA], or other ischemic event)
    • Myocardial infarction
    • Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study)
    • Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
    • Any of the following within 28 days before the first dose of study treatment
    • Active peptic ulcer disease
    • Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
    • Malabsorption syndrome
    • Any of the following within 6 months before the first dose of study treatment:
    • Abdominal fistula
    • Gastrointestinal perforation
    • Bowel obstruction or gastric outlet obstruction
    • Intra-abdominal abscess; Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 6 months before the first dose of study treatment
    • Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
    • Other clinically significant disorders such as:
    • Active infection requiring systemic treatment within 28 days before the first dose of study treatment; patients with HIV infection will be eligible provided they meet the criteria; patients with known hepatitis B infection should be screened for active disease prior to study participation
    • Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
    • History of organ transplant
    • Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
    • History of major surgery as follows:
    • Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wound complications
    • Minor surgery within 1 months of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications
    • In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery
    • The subject is unable to swallow tablets that are whole (do not crush or chew or administer via nasogastric [NG]-tube)
    • The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization; note: If initial QTcF is found to be > 500 ms, two additional electrocardiogram (ECGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard
    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib (XL184)
    • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with cabozantinib

    Principal Investigator: Robert A Baiocchi, MD, PhD

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  • open for enrollment

    An Open-Label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of VX-970 in Combination With Cytotoxic Chemotherapy

    Protocol: OSU-13211

    Eligibility:

    Inclusion Criteria:

    Disease status

    • Parts A and B: Histologically confirmed advanced solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective, or for whom regimens containing gemcitabine, cisplatin, and/or etoposide might be considered, and with measurable disease according to RECIST criteria
    • Part C1:
    • Advanced (Stage IIIB or IV, not eligible for resection or definitive radiotherapy), histologically confirmed squamous non-small cell lung cancer (NSCLC) and who have not previously received chemotherapy for metastatic disease.
    • Either has lesion amenable to biopsy before Day 1 or available archived tumor sample
    • Measurable disease according to RECIST criteria
    • Part C2:
    • Advanced (locally-advanced incurable or metastatic) histologically confirmed estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) negative breast cancer.
    • Received a prior taxane-based regimen and no more than 1 additional regimen in the metastatic setting
    • Either has lesion amenable to biopsy before Day 1 or available archived tumor sample d. Measurable disease according to RECIST criteria
    • Part C3:
    • Histologically confirmed SCLC that has relapsed from, or was refractory to, prior chemotherapy. Refractory disease is defined as relapse within 90 days of completing chemotherapy, or lack of tumor response while on therapy.
    • Either has lesion amenable to biopsy before Day 1 or available archived tumor sample
    • Measurable disease according to RECIST criteria
    • Hematological and biochemical indices within protocol specified ranges at screening.

    Exclusion Criteria:

    • Radiotherapy (except for palliative reasons) endocrine therapy, immunotherapy, or chemotherapy during the previous 4 weeks
    • Parts A and B:
    • Greater than 6 cycles of prior treatment with cisplatin and/or carboplatin.

    (a) History of prior dose reductions or dose interruptions while receiving cisplatin or carboplatin due to toxicity from the platinum or intolerance to either agent.

    • More than 2 prior distinct chemotherapy regimens used for treatment of advanced stage disease containing DNA damaging agents:
    • Subjects with a history of Grade 3 or 4 thrombocytopenia or Grade 4 neutropenia while receiving prior therapy with cisplatin, carboplatin, or any of the DNA damaging agents listed above.
    • Part C1:
    • prior platinum therapy for squamous NSCLC
    • Received prior treatment for metastatic NSCLC
    • Part C2:
    • More than 2 prior chemotherapy regimens for the treatment of metastatic breast cancer
    • Any prior platinum therapy for breast cancer in any setting
    • Part C3:
    • In relapsed SCLC, more than 2 prior chemotherapy regimens or, in refractory SCLC, more than 1 prior chemotherapy regimen
    • Has not received at least 1 cycle of platinum based chemotherapy for SCLC
    • Unresolved toxicity of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater from previous anti-cancer therapy or radiotherapy
    • History of brain or leptomeningeal metastases
    • Female subjects who are already pregnant or lactating, or plan to become pregnant within 6 months of the last dose of study drug are excluded. Female subjects of childbearing potential must adhere to contraception guidelines
    • Male subjects with partners of child-bearing potential must agree to adhere to contraception guidelines. Men with pregnant or lactating partners or partners who plan to become pregnant during the study or within 6 months of the last dose of study drug are excluded
    • Major surgery ≤2 weeks before starting study drug, or incomplete recovery from a prior major surgical procedure
    • Serious cardiac or other co-morbid disease, as specified in the protocol
    • Prior bone marrow transplant or extensive radiotherapy to greater than 15% of bone marrow
    • Part C:
    • Current malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin

    Principal Investigator: Robert Wesolowski, MD

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  • open for enrollment

    Safety Study of Unlicensed, Investigational Cord Blood Units Manufactured by the NCBP for Unrelated Transplantation

    Protocol: OSU-12097

    Eligibility:

    Inclusion Criteria: 1. Diagnosis: Patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment. 2. Patients: Patients of any age and either gender 3. Cord blood product manufactured by the NCBP (at least one, if the graft contains more than one units) Exclusion Criteria: 1. Patients who are receiving licensed cord blood products (only) 2. Patients who are receiving unlicensed cord blood products from other banks (only) 3. Patients who are transplanted at non-US transplant centers 4. Patients who are receiving cord blood products that will be "manipulated" post-thaw (e.g., ex vivo expansion, incubation in vitro, etc.)

    Principal Investigator: Sumithira Vasu, MD

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