S1014 Abiraterone Acetate in Treating Patients With Prostate Cancer Who Have Undergone Initial Hormone Therapy

Study Overview
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Brief Summary
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RATIONALE: Androgens can cause the growth of prostate cancer cells. Antiandrogen drugs, such as abiraterone acetate, may lessen the amount of androgens made by the body. It may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying the side effects and how well abiraterone acetate works in treating patients with prostate cancer who have undergone initial hormone therapy.

Detailed Description
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OBJECTIVES: Primary To assess the rate of achieving a prostate-specific antigen (PSA) of ≤ 0.2 ng/mL with abiraterone acetate therapy in men with metastatic prostate cancer with a sub-optimal response to androgen-deprivation therapy (ADT). Secondary To assess the overall survival and objective progression-free survival of this group of patients. To assess PSA partial response. To evaluate the qualitative and quantitative toxicity of abiraterone acetate. OUTLINE: This is a multicenter study. Patients receive abiraterone acetate orally daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive androgen blockade with GNRH agonist (goserelin acetate or leuprolide acetate) or a GNRH antagonist (degarelix) per the treating physician and this will be given continuously until evidence of disease progression. Bilateral surgical orchiectomy is also acceptable. After completion of study therapy, patients are followed up every 3 months for 1 year and then every 6 months for up to 3 years.

Official Title
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Abiraterone Acetate Treatment for Prostate Cancer Patients With a PSA of More Than Four Following Initial Androgen Deprivation Therapy Phase II

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: abiraterone acetate
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically proven diagnosis of adenocarcinoma of the prostate Metastatic (M1) disease as evidenced by soft tissue and/or bony metastases at the time of initiation of androgen-deprivation therapy (ADT) Must have at least one of the following: Visceral disease (liver, lung, other viscera) Bone metastases to sites in either the axial (spine, pelvis, ribs, or skull) and/or the appendicular (clavicle, humerus, or femur) skeleton Distant lymph node disease (e.g., above the aortic bifurcation, etc.) No small cell or neuroendocrine prostate cancer Patients must be receiving ADT (e.g., gonadotropin-releasing hormone [GNRH] antagonist, with or without antiandrogen) prior to entering this study Degarelix, a FDA-approved GNRH antagonist, is an acceptable form of ADT Bilateral surgical orchiectomy is also acceptable Suboptimal response to ADT induction as defined by the following criteria: Declining PSA (current PSA is less than the PSA prior to starting ADT) that fails to reach 4 ng/mL or below despite continuous ADT PSA of > 4 ng/mL must be observed between 6-12 months after the initiation of ADT Documentation of failure to achieve this PSA of ≤ 4 ng/mL must be within 28 days of registration The PSA must be obtained after any applicable antiandrogen washout period If the PSA is declining or stable (defined as a PSA rise ≤ 0.1 ng/mL from nadir) and the patient is on an antiandrogen, they must remain on the antiandrogen Patients with stable or declining PSA who have had previous antiandrogen exposure, but are not taking an antiandrogen at the time of registration, must wait at least 6 weeks from the last antiandrogen dose before registration and still demonstrate a stable or falling PSA which is > 4 ng/mL by month 12, in order to be eligible If the PSA is rising and they are on an antiandrogen, formal antiandrogen washout must be performed (4 weeks for flutamide and 6 weeks for bicalutamide and nilutamide with no evidence of a falling PSA after washout) No patients with radiographic progression when compared to available imaging studies performed prior to starting the GNRH agonist/antagonist therapy Patients who have measurable disease must have radiographic assessment (at least an abdominal/pelvic CT scan) within 28 days prior to registration Non-measurable disease must be assessed (i.e., bone scan) within 42 days prior to registration No patients with a history of brain metastases or who currently have treated or untreated brain metastases Patients with clinical evidence of brain metastases must have a brain CT scan or MRI negative for metastatic disease within 56 days prior to registration PATIENT CHARACTERISTICS: Zubrod performance status 0-2 ANC ≥ 1,500/μL Platelet count ≥ 100,000/μL Hemoglobin ≥ 10 g/dL Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) OR creatinine clearance ≥ 60 mL/min Bilirubin ≤ 1.5 times ULN (unless documented Gilbert disease) AST and ALT < 1.5 times ULN Potassium ≥ 3.5 mmol/L Patient must have a testosterone value of < 50 ng/dL obtained within 28 days prior to registration Patients must have controlled blood pressure defined as systolic blood pressure < 160 mm Hg and diastolic blood pressure < 95 mm Hg Patients with a history of hypertension are eligible provided blood pressure is controlled by anti-hypertensive treatment Patients who have partners of child-bearing potential must be willing to use a method of birth control with adequate barrier protection during the study and for 1 week after the last study drug administration Must be able to take oral medication without crushing, dissolving, or chewing tablets Patients must not have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of abiraterone acetate No other prior malignancy is allowed except for any of 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 Any other cancer from which the patient has been disease-free for 5 years No patients with active or symptomatic viral hepatitis or chronic liver disease No moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment No history of NYHA class III or IV heart failure Patients must have LVEF ≥ 50% No known allergies, hypersensitivity, or intolerance to abiraterone acetate, prednisone, or their excipients PRIOR CONCURRENT THERAPY: See Disease Characteristics Patients with a history of prior neoadjuvant or adjuvant GNRH agonist/antagonist therapy (related to previous surgery or radiation) are eligible provided they finished this therapy at least two years prior to registration Prior enrollment to SWOG-S0925 (either arm) is not exclusionary At least 6 weeks since prior and no concurrent finasteride or dutasteride At least 28 days since prior radiotherapy or surgery and recovered At least 4 weeks since prior investigational products At least 4 weeks since prior flutamide (6 weeks for bicalutamide and nilutamide) with no evidence of a falling PSA No other concurrent oral antiandrogen No prior or concurrent cytotoxic chemotherapy or radiopharmaceuticals for prostate cancer No prior or concurrent ketoconazole for the treatment of prostate cancer Not requiring more than 10 mg a day of prednisone for another medical indication Not planning to receive any concurrent cytotoxic chemotherapy, immunotherapy, surgery, or radiotherapy during protocol treatment No concurrent hormonal-acting agents, including diethylstilbestrol/DES, aldosterone, PC-SPES, or spironolactone No concurrent antifungal medication (e.g., fluconazole or itraconazole) No medications that alter cardiac conduction No prior Provenge (sipuleucel-T)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abiraterone acetate + prednisone<br>Abiraterone, 1,000 mg, oral (on an empty stomach at least 2 hours after or 1 hour before eating); to be taken daily Prednisone, 5 mg, oral, 5 mg twice daily | Drug: abiraterone acetate<br>* 1,000 mg, oral (on an empty stomach at least 2 hours after or 1 hour before eating); taken daily<br>Drug: Prednisone<br>* 5 mg, oral, 5 mg twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Undetectable PSA | undetectable PSA defined as <= 0.2 ng/mL. Patients not responding in the first year were deemed non-responders. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With PSA Partial Response | PSA reduction to < 4 ng/ml, but >0.2 ng/ml | 12 months | 
| Objective Progression-free Survival | Progression defined as unequivocal progression of disease, progressive disease as defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), progressive disease as defined by the Prostate Cancer Clinical Trials Working Group bone scan progression criteria, or death due to disease. | 3 years | 
| Overall Survival |  | 3 years | 
| Number of Patients With Toxicity of Abiraterone Acetate | Only adverse events that are possibly, probably or definitely related to study drug are reported. | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, hormone-resistant prostate cancer, stage IV prostate cancer, recurrent prostate cancer