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

Inclusion Criteria

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)