The primary goal is to prospectively estimate the median PFS of African American and
Caucasian men with mCRPC taking apalutamide, abiraterone acetate, and prednisone. Secondary
objectives include: PSA kinetics: to determine the duration of PSA response, time to nadir,
and percent of men who achieve a PSA < 0.1; Radiographic assessments: to estimate the rate of
objective response and incidence of bone flares; Safety (NCI CTC v4.0) and tolerability,
particularly incidence and grade of hypertension in the two populations.
This is a non-comparative pilot open-label, parallel arm, multicenter study of apalutamide
and abiraterone acetate in African American and Caucasian men with mCRPC. It is anticipated
that 3 additional sites will be needed to accrue 100 subjects (50 African American and 50
Caucasian) over a 24 month accrual period. The study agents will be administerd at the
following doses: apalutamide 240mg orally once daily, abiraterone acetate 1000mg orally once
daily, and prednisone 5 mg BID in 4-week cycles throughout the treatment period.
Fifty (50) patients will be enrolled in each group (AA and Caucasians). The proportion of
patients who experience PSA decline of 30%, 50% and 90% will be estimated with exact 95%
confidence intervals based on the binomial distribution will be computed. In addition, post
therapy changes in PSA will be explored as a continuous outcome. The Kaplan-Meier product
limit method will be used to estimate the rPFS, biochemical PFS and overall survival
1. Male, age ≥ 18 years
2. Karnofsky performance status ≥ 70 (Appendix 1)
3. Life expectancy of ≥ 12 months as determined by treating investigator
4. Written Authorization for Use and Release of Health and Research Study Information
(HIPAA authorization per institutional requirements)
5. Willing/able to adhere to the prohibitions and restrictions specified in this protocol
6. Willing to take abiraterone acetate on an empty stomach, and should be able to swallow
tablets whole, without crushing/chewing tablets. Must have the ability to swallow,
retain, and absorb oral medication.
7. Medications known to lower the seizure threshold (see list under prohibited meds,
appendix 2) must be discontinued or substituted at least 4 weeks prior to study entry
8. Agrees to use a condom (even men with vasectomies) and another effective method of
birth control if he is having sex with a woman of childbearing potential or agrees to
use a condom if he is having sex with a woman who is pregnant while on study drug and
for 3 months following the last dose of study drug. Must also agree not to donate
sperm during the study and for 3 months after receiving the last dose of study drug.
Abstinence is an acceptable method of birth control.
9. Adequate bone marrow function as shown by: ANC ≥ 1.0 x 109/L, Platelets ≥ 100 x 109/L,
Hb≥9 g/dL, (independent of transfusion and/or growth factors within 3 months prior to
Cycle 1 Day 1)
10. Serum potassium ≥ 3.5 mEq/L
11. Serum albumin of ≥ 3.0 g/dl
12. AST/SGOT and ALT/SGPT <2.5 x Institutional Upper Limit of Normal (ULN)
13. Serum total bilirubin ≤ 1.5 x Institutional ULN (Note: In subjects with Gilbert's
syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and
if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
14. GFR ≥45 mL/min
15. Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic
variants of prostate cancer comprising of >50% of the tumor including neuroendocrine
features and small cell carcinoma of the prostate are excluded.
16. Radiographic evidence of metastatic disease based on RECIST 1.1 Criteria OR by
prostate cancer-specific PET imaging. Evaluable non-target lesions and/or bone only
metastasis are permitted per RECIST 1.1 and PCWG3 guidelines. Non-target, pathological
lymph nodes ≥ 10 mm and less than 15 mm in the short axis are permitted.
17. Ongoing ADT using an LHRH agonist (e.g. leuprolide, goserelin) or antagonist (e.g.
degarelix) must continue on therapy unless prior bilateral orchiectomy has been
18. PSA ≥ 2.0 ng/mL
19. Evidence of castration resistant disease in the setting of ongoing ADT (medical or
surgical) as evidenced by one of the following:
- Absolute rise in PSA of 2.0 ng/mL or an increase >25% from the nadir, minimum 2
consecutive rising PSA levels with an interval of ≥ 1 week between each PSA
- CT or MRI based evidence of disease progression (soft tissue, nodal or visceral
disease progression) according to PCWG3 criteria or RECIST 1.1 criteria, OR
- At least 1 new bone scan lesion as compared to the most immediate prior
20. A minimum of 2 weeks elapsed off of antiandrogen therapy prior to start of study drug
(i.e. flutamide, nilutamide, bicalutamide.)
21. A minimum of 2 weeks elapsed off of sipuleucel-T and radiation therapy prior to start
of study drug
22. A minimum of 4 weeks from any major surgery prior to start of study drug.
23. Self-reported race of either African American or Caucasian.
24. Ability to understand and the willingness to sign a written informed consent document.
If the subject is unable to understand the consent due to comorbidity, such as
Alzheimer's disease, consent by a legally authorized representative and assent by the
subject will be obtained.
1. Prior treatment with abiraterone acetate, enzalutamide, apalutamide (ARN-509),
galaterone (TOK-001), orteronel (TAK-700), or similar agent
2. Active infection or other medical condition that would make prednisone/prednisolone
(corticosteroid) use contraindicated
3. Active or symptomatic infection including HIV, viral hepatitis or chronic liver
4. Any chronic medical condition requiring a higher dose of corticosteroid than 5mg
5. Have known allergies, hypersensitivity, or intolerance to abiraterone acetate,
apalutamide or prednisone or their excipients.
6. Pathological finding consistent with small cell carcinoma of the prostate
7. Symptomatic liver or visceral organ metastasis
8. Have a history of gastrointestinal disorders (medical disorders or extensive surgery)
that may interfere with the absorption of the study agents
9. Known brain metastasis
10. Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC. Note:
sipulecel-T is permitted with a 2-week washout.
11. Previously treated with ketoconazole for prostate cancer for greater than 7 days
12. Prior systemic treatment with an azole anti-fungal drug (e.g. fluconazole,
itraconazole) within 4 weeks of Cycle 1, Day 1.
13. Uncontrolled hypertension (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg). Patients
with a history of hypertension are allowed provided blood pressure is controlled by
14. Poorly controlled diabetes, FBS ≥200 mg/dL
15. History of pituitary or adrenal dysfunction
16. Symptomatic Atrial Fibrillation, or other symptomatic cardiac arrhythmia
17. Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of
recurrence within 24 months
18. History of any of the following:
- Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke
within 6 months of Cycle 1 Day 1, brain arteriovenous malformation, Schwannoma,
meningioma, or other benign CNS or meningeal disease which may require treatment
with surgery or radiation therapy)
- Severe or unstable angina, myocardial infarction, symptomatic congestive heart
failure, arterial or venous thromboembolic events (e.g., pulmonary embolism,
cerebrovascular accident including transient ischemic attacks), or clinically
significant ventricular arrhythmias within 6 months prior to first dose of study
drug. Venous thrombolic events within 6 months are permitted IF they are not
attributed to prostate cancer (in the opinion of the treating physician).
19. Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment.
20. Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a
narrow therapeutic index. If an alternative treatment cannot be used, exercise caution
and consider a dose reduction of the concomitant CYP2D6 substrate
21. Baseline moderate or severe hepatic impairment (Child Pugh Class B & C)
22. Use of herbal products that may decrease PSA levels (i.e., saw palmetto) refer to
section 8.3.2 (no washout period required)
23. Administration of an investigational therapeutic within 30 days prior to Cycle 1, Day
24. Any condition which, in the opinion of the investigator, would preclude participation
in this trial