Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Ph III Comparing ADT+TAK-700 w ADT+Bicalutamide in Newly Diagnosed Met Hormone Sensitive Prostate Ca

Protocol: SWOG-S1216

Full Title

A Phase III Randomized Trial Comparing Androgen Deprivation Therapy + TAK-700 With Androgen Deprivation Therapy + Bicalutamide in Patients With Newly Diagnosed Metastatic Hormone Sensitive Prostate Cancer

Study Objective

PRIMARY OBJECTIVES:

I. To compare overall survival in newly diagnosed metastatic prostate cancer patients randomly assigned to androgen deprivation therapy (ADT) (luteinizing hormone releasing hormone analogue [LHRHa] or orchiectomy) + TAK-700 (orteronel) versus ADT (LHRHa or orchiectomy) + bicalutamide.

SECONDARY OBJECTIVES:

I. To compare progression free survival between the two arms.

II. To compare distributions of prostate specific antigen (PSA) response (< 0.2 vs. 0.2-4.0 vs. > 4.0 ng/ml) between the treatment arms at 7 months post-randomization.

III. To compare the qualitative and quantitative adverse events from each treatment arm.

IV. To characterize the long-term survival in both treatment arms after 10 years of follow-up.

TERTIARY OBJECTIVES:

I. To validate the prognostic and predictive value of markers of bone turnover in newly-diagnosed metastatic hormone sensitive prostate cancer patients treated with TAK-700.

II. To bank plasma/whole blood and tissue specimens for future use.

III. To evaluate genomic variants and gene expression of androgen pathway genes and their correlation with response to therapy (ADT + TAK-700 vs. ADT + bicalutamide).

OUTLINE: Patients who are not surgically castrated are randomized to 1 of 2 treatment arms. Patients who are surgically castrated receive only orteronel (Arm I) or bicalutamide (Arm II).

ARM I: Patients receive goserelin acetate or leuprolide acetate subcutaneously (SC) or intramuscularly (IM) once every 3 months and orteronel orally (PO) twice daily (BID).

ARM II: Patients receive goserelin acetate or leuprolide acetate as in Arm I and bicalutamide PO once daily (QD).

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually for up to 10 years.

Are you eligible?

Inclusion Criteria:

There are two patient populations eligible for the study: those who have not started any therapy with LHRH agonist or antagonist (or orchiectomy) (Early Induction Group) and those who have already started therapy with LHRH agonist or antagonist (or orchiectomy) within the 30 days prior to registration (Late Induction Group); patients must be registered within 30 days of first injection of the LHRH agonist or antagonist (or orchiectomy)

Disease Related Criteria:

All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate; all patients must have metastatic disease as evidenced by soft tissue and/or bony metastases prior to initiation of androgen deprivation therapy

Patients who have not yet started androgen deprivation therapy (LHRH agonist/antagonist or orchiectomy) and will not have an LHRH agonist injection until after randomization (early induction group) must have radiographic assessments of all disease including bone scan (or positron emission tomography [PET] scan) within 42 days prior to registration; patients who have started androgen deprivation therapy (LHRH agonist/antagonist or orchiectomy) prior to registration (late induction group) must have radiographic assessments including bone scan (or PET scan) within 42 days prior to start of androgen deprivation therapy (if scans have not been obtained prior to LHRH agonist/antagonist or orchiectomy they must be done within 42 days prior to registration); all disease must be assessed and documented on the Baseline Tumor Assessment Form; NOTE: Androgen deprivation therapy does not include treatment with anti-androgens such as bicalutamide or flutamide or five alpha reductase inhibitors such as finasteride or dutasteride

Patients with known brain metastases are not eligible; brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms suggestive of brain metastasis; but, if brain imaging studies are performed, they must be negative for disease

Patients who are deemed to have high-risk or extensive metastatic, hormone sensitive prostate cancer (mHSPC) per “clinical judgment” of the treating physician are eligible for enrollment if they are unsuitable candidates for docetaxel or if they have declined docetaxel therapy

Prior Therapy Criteria:

Patients may have received prior androgen deprivation therapy (ADT) - neoadjuvant and/or adjuvant setting only, but it must not have lasted for more than 36 months (note that this is NOT the same as “late induction” as described in Section 5.1b above); single or combination therapy allowed; at least 6 months must have elapsed since completion of androgen deprivation therapy in the neoadjuvant and/or adjuvant setting, and serum testosterone must be > 50 ng/dL (non-castrate levels) within 28 days prior to registration for early induction patients; Note: serum testosterone assessment is required for eligibility for only those with prior treatment with ADT

Patients must not have received prior and/or must not have any plans for receiving concomitant therapy with ketoconazole, aminoglutethimide, or abiraterone acetate, or enzalutamide (MDV3100); concurrent megestrol for hot flashes is allowed

Patients must not have received any prior cytotoxic chemotherapy for metastatic prostate cancer; prior cytotoxic chemotherapy with curative intent in the neoadjuvant or adjuvant setting is allowed; at least 2 years must have elapsed since completion of cytotoxic chemotherapy in the neoadjuvant and/or adjuvant setting

Patients may have received prior surgery; for all major surgeries, at least 14 days must have elapsed since completion and patient must have recovered from all major side effects of surgery per investigator’s assessment

Patient may have received or plan to receive concurrent bone targeting agents that do not have an effect on PSA (e.g. denosumab or bisphosphonate)

Patient must have no plans to receive any other experimental therapy while on the protocol treatment; previous experimental therapy must have been completed at least 28 days prior to registration

In the late induction group, patients must have had no more than 30 days of prior castration (medical or surgical) for metastatic prostate cancer prior to registration; the start date of medical castration is considered the day the patient first received an injection of a LHRH agonist/antagonist (or orchiectomy), not an oral antiandrogen

If the method of castration was luteinizing hormone releasing hormone (LHRH) agonists (i.e., leuprolide or goserelin), the patient must be willing to continue the use of LHRH agonist and add bicalutamide or TAK-700 (according to randomization) during protocol treatment

If the patient was on an antiandrogen (e.g. bicalutamide, flutamide), the patient must be willing to switch over to bicalutamide or TAK-700 (according to randomization); there is no limit on how many days a patient may have been on an antiandrogen (e.g. bicalutamide, flutamide) or a five alpha reductase inhibitor (e.g. finasteride or dutasteride) prior to going on study and no washout is required

If the method of castration was LHRH antagonists (i.e. Degarelix), the patient must be willing to switch to an LHRH agonist during protocol treatment

Clinical/Laboratory Criteria:

Patients must have a complete physical examination and medical history within 28 days prior to registration

Patients must have a PSA >= 2 ng/mL obtained within 90 days prior to registration

A dual-energy X-ray absorptiometry (DEXA) scan must be obtained within 2 years prior to registration

Patients must not have New York Heart Association class III or IV heart failure at the time of screening; patients must not have any thromboembolic event, unstable angina pectoris, myocardial infarction, or serious uncontrolled cardiac arrhythmia within 6 months prior to registration (Note: Patients with congenital long AT syndrome, congestive heart failure, frequent electrolyte abnormalities, and patients taking drugs known to prolong the QT interval may be at increased risk)

Patient must have a corrected QT interval (QTc) interval < 461 msec on the 12 lead electrocardiogram (ECG) within 42 days prior to registration, patients with asymptomatic or incidental bundle branch blocks may have QTc measured by a cardiologist or standard formulas such as Bazett’s or Fridericia’s to adjust for pre-existing blocks

Patients must have a left ventricular ejection fraction (LVEF) >= 50% by echocardiogram or multiple gated acquisition (MUGA) scan within 42 days prior to registration

Patients must have blood pressure measured within 14 days prior to registration; patients must not have uncontrolled hypertension (defined as blood pressure > 160 mmHg systolic and > 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart) despite appropriate medical therapy; Note: patients may be rescreened after adjustments of antihypertensive medications

Bilirubin =< 2 x institutional upper limit of normal (ULN); these results must be obtained within 28 days prior to registration

Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x institutional ULN, or =< 5 x institutional ULN if liver metastases are present; these results must be obtained within 28 days prior to registration

Calculated creatinine clearance >= 40 mL/min using a serum creatinine or by 24-hour urine creatinine obtained within 28 days prior to registration

Leukocytes >= 3,000/mcL; these results must be obtained within 28 days prior to registration

Absolute neutrophil count (ANC) >= 1,500/mcL; these results must be obtained within 28 days prior to registration

Hemoglobin >= 9 g/dL; these results must be obtained within 28 days prior to registration

Platelets >= 100,000/mcL; these results must be obtained within 28 days prior to registration

Patient must not be known to have human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with participation in this study; patients will be tested for hepatitis B or C or HIV infection during screening if they are considered by the investigator to be at higher risk for these infections and have not been previously tested

Patients with a known history of primary and secondary adrenal insufficiency are not eligible

Patient must not be known to have hypersensitivity to TAK-700, to TAK-700 metabolites, to bicalutamide, or to LHRH agonist

Patients must not have known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of TAK-700, including difficulty swallowing oral medications per investigator’s clinical judgement

Patients must have a Zubrod performance status of 0 - 2; Zubrod performance status 3 will be allowed if from bone pain only

No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin 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 5 years

Men of reproductive potential and those who are surgically sterilized (i.e., post-vasectomy) must agree to practice effective barrier contraception or agree to abstain from intercourse while receiving treatment on this study and for at least 4 months after protocol treatment ends

Specimen Submission Criteria:

Patients must be offered the opportunity to participate in specimen banking for future use to include translational medicine studies

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

Voluntary written informed consent must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

As a part of the 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

Prostate Cancer Genitourinary Cancers