Apalutamide and Abiraterone Acetate in African American and Caucasian Men With Metastatic Castrate Resistant Prostate Cancer

NCT ID: NCT03098836

Last Updated: 2025-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-10
• Study Completion Date: 2024-07-09

Brief Summary

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 distributions.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Caucasian

Group Type: EXPERIMENTAL

ARN-509

Intervention Type: DRUG

240 mg orally daily

Abiraterone Acetate

Intervention Type: DRUG

1000 mg orally daily

Prednisone

Intervention Type: DRUG

5 mg orally twice daily (for total daily dose 10 mg)

African American

Group Type: EXPERIMENTAL

ARN-509

Intervention Type: DRUG

240 mg orally daily

Abiraterone Acetate

Intervention Type: DRUG

1000 mg orally daily

Prednisone

Intervention Type: DRUG

5 mg orally twice daily (for total daily dose 10 mg)

Interventions

ARN-509

240 mg orally daily

Intervention Type: DRUG

Abiraterone Acetate

1000 mg orally daily

Intervention Type: DRUG

Prednisone

5 mg orally twice daily (for total daily dose 10 mg)

Intervention Type: DRUG

Other Intervention Names

apalutamide; Zytiga

Eligibility Criteria

Inclusion Criteria

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 performed.

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 level, OR
• 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 radiologic studies.

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.

Exclusion Criteria

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 disease

4. Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone bid

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 anti-hypertensive treatment

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 1

24. Any condition which, in the opinion of the investigator, would preclude participation in this trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role: collaborator

Daniel George, MD

OTHER

Sponsor Role: lead

Responsible Party

Daniel George, MD

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Daniel J. George, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Cancer Institute

Locations

Tulane University

New Orleans, Louisiana, United States

Chesapeake Urology Associates

Baltimore, Maryland, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Duke Cancer Center Cary

Cary, North Carolina, United States

UNC Lineberger Cancer Center

Chapel Hill, North Carolina, United States

Johnston Hematology and Oncology of Clayton

Clayton, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Maria Parham Hospital

Henderson, North Carolina, United States

Scotland Memorial Hospital

Laurinburg, North Carolina, United States

Southeastern Regional

Lumberton, North Carolina, United States

Johnston Memorial Hospital

Smithfield, North Carolina, United States

Spartanburg Regional

Spartanburg, South Carolina, United States

Virginia Oncology Associates

Hampton, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Pro00075097

Identifier Type: -

Identifier Source: org_study_id