OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive ADT per standard of care. Beginning 2 months after start of ADT,
patients also receive abiraterone acetate and prednisone per standard of care for at least 6
months in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive ADT, abiraterone acetate, and prednisone as in Arm I. Beginning 8-10
weeks after starting ADT and within 1 week of starting abiraterone acetate, patients also
undergo 3-5 fractions of neutron radiation therapy for 2 weeks in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 4 weeks for 6 months.
Inclusion Criteria:
- Pathologically proven (either histologic or cytologic) diagnosis of prostate
adenocarcinoma with < 50% neuroendocrine differentiation or small cell histology.
- At least one site of nodal or distant metastatic disease that is measurable by
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or a bony
metastasis that is evaluable on both computed tomography (CT) and bone scan.
- No prior orchiectomy.
- No androgen deprivation therapy such as treatment with antiandrogens, luteinizing
hormone-releasing hormone (LHRH) agonists or antagonists for at least one year prior
to trial enrollment, and testosterone must be inside normal range prior to trial
enrollment if there is prior history of ADT.
- No other systemic anti-cancer therapy for at least 1-year prior to enrollment.
- Prior prostate-directed therapies such as prostatectomy or cryotherapy are allowed.
- Prior radiation treatments are allowed (prostate or metastatic sites) but must have
been completed at least 3 months prior to starting ADT for this trial.
- White blood cell (WBC) > 3000/mm^3.
- Absolute neutrophil count (ANC) > 1000/mm^3.
- Platelets > 100,000/mm^3.
- Creatinine < 1.5 institutional upper limit of normal (ULN) or calculated creatinine
clearance > 30 ml/min.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin
< 3 x institutional ULN (unless patient has documented Gilbert's syndrome).
- No steroids for at least 2 weeks prior to enrollment, and patient must not be expected
to require steroids during the study period, other than the typical low dose steroid
that is given with abiraterone (typically prednisone or prednisolone at 5 mg twice
daily).
- Zubrod performance status 0-2.
- Patient must sign study specific informed consent prior to study entry.
- Men who are sexually active must use medically acceptable forms of contraception.
Exclusion Criteria:
- Other illnesses with a life expectancy of less than 6 months, including but not
limited to unstable angina, symptomatic congestive heart failure, cardiac arrhythmias.
- Psychological or social issues that would prevent patients from informed consent or
complying with study requirements.
- Subject has a history of unexplained loss of consciousness or transient ischemic
attack within 12 months of treatment start.
- Individuals on active treatment for a different cancer are excluded. Individuals with
a history of other malignancies are eligible if they are deemed by the investigator to
be at low risk for recurrence of that malignancy.
- Known brain metastasis.
- Known allergies, hypersensitivity, or intolerance to abiraterone or prednisone.
- Prior ADT less than a year, or greater than two months, prior to trial enrollment or
prior ADT with testosterone less than normal.
- There is a potential drug interaction when abiraterone is concomitantly used with a
CYP2D6 substrate narrow therapeutic index (e.g., thioridazine, dextromethorphan), or
strong CYP3A4 inhibitors (e.g., atazanavir, erythromycin, indinavir, itraconazole,
ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and
voriconazole) or strong inducers (e.g., carbamazepine, phenobarbital, phenytoin,
rifabutin, rifampin, rifapentine). Caution should be used when patients are on one of
these drugs.
- Patients with a history of pituitary or adrenal dysfunction, active or symptomatic
viral hepatitis, human immunodeficiency virus (HIV), or chronic liver disease are not
eligible.
- Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg
prednisone/prednisolone once daily.
