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

NCT03098836 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro00075097
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 14

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

Keywords

metastatic; castrate resistant

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With 2-Year Progression-Free Survival (PFS)

  Radiographic PFS based on PCWG2 criteria or based on the onset of a skeletal related event. Imaging obtained every 12 weeks. Kaplan-Meier estimate of percentage of participants is reported.

  every 12 weeks, up to 2 years

Secondary Outcomes (7)

• 2-year PSA Progression Free Survival

  every 4 weeks, up to 2 years

• Time to PSA Nadir

  every 4 weeks, up to 2 years

• Percent of Men Who Achieve a PSA < 0.1

  every 4 weeks, up to 2 years

• Radiologic Response Rates

  every 12 weeks, up to 2 years

• Percentage of Participants With Bone Flares

  12 weeks

Study Arms (2)

Caucasian

EXPERIMENTAL

Drug: ARN-509; Drug: Abiraterone Acetate; Drug: Prednisone

African American

EXPERIMENTAL

Drug: ARN-509; Drug: Abiraterone Acetate; Drug: Prednisone

Interventions

ARN-509 DRUG

240 mg orally daily

Also known as: apalutamide

African American; Caucasian

Abiraterone Acetate DRUG

1000 mg orally daily

Also known as: Zytiga

African American; Caucasian

Prednisone DRUG

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

African American; Caucasian

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male, age ≥ 18 years
• Karnofsky performance status ≥ 70 (Appendix 1)
• Life expectancy of ≥ 12 months as determined by treating investigator
• Written Authorization for Use and Release of Health and Research Study Information (HIPAA authorization per institutional requirements)
• Willing/able to adhere to the prohibitions and restrictions specified in this protocol
• 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.
• 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
• 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.
• 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)
• Serum potassium ≥ 3.5 mEq/L
• Serum albumin of ≥ 3.0 g/dl
• AST/SGOT and ALT/SGPT \<2.5 x Institutional Upper Limit of Normal (ULN)
• 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)
• GFR ≥45 mL/min
• 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.

You may not qualify if:

• Prior treatment with abiraterone acetate, enzalutamide, apalutamide (ARN-509), galaterone (TOK-001), orteronel (TAK-700), or similar agent
• Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
• Active or symptomatic infection including HIV, viral hepatitis or chronic liver disease
• Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone bid
• Have known allergies, hypersensitivity, or intolerance to abiraterone acetate, apalutamide or prednisone or their excipients.
• Pathological finding consistent with small cell carcinoma of the prostate
• Symptomatic liver or visceral organ metastasis
• Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
• Known brain metastasis
• Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC. Note: sipulecel-T is permitted with a 2-week washout.
• Previously treated with ketoconazole for prostate cancer for greater than 7 days
• Prior systemic treatment with an azole anti-fungal drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1.
• 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
• Poorly controlled diabetes, FBS ≥200 mg/dL
• History of pituitary or adrenal dysfunction

Sponsors & Collaborators

• Daniel George, MD: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (14)

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Chesapeake Urology Associates

Baltimore, Maryland, 21204, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Duke Cancer Center Cary

Cary, North Carolina, 27518, United States

Location

UNC Lineberger Cancer Center

Chapel Hill, North Carolina, 27514, United States

Location

Johnston Hematology and Oncology of Clayton

Clayton, North Carolina, 27520, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Maria Parham Hospital

Henderson, North Carolina, 27536, United States

Location

Scotland Memorial Hospital

Laurinburg, North Carolina, 28352, United States

Location

Southeastern Regional

Lumberton, North Carolina, 28358, United States

Location

Johnston Memorial Hospital

Smithfield, North Carolina, 27577, United States

Location

Spartanburg Regional

Spartanburg, South Carolina, 29303, United States

Location

Virginia Oncology Associates

Hampton, Virginia, 29303, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

apalutamide; Abiraterone Acetate; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Daniel George, MD
• Organization: Duke University Medical Center

daniel.george@duke.edu

(919) 668-8108

Study Officials

• Daniel J. George, MD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 28, 2017
• First Posted: April 4, 2017
• Study Start: July 10, 2017
• Primary Completion: July 9, 2024
• Study Completion: July 9, 2024
• Last Updated: September 12, 2025
• Results First Posted: September 12, 2025

Record last verified: 2025-09

Locations

US (14)