Race Impact on Efficacy of Niraparib Plus Abiraterone Acetate and Prednisone in Patients With Homologous Repair Deficient Castration-resistant Prostate Cancer (REPRESENTATION)

This is an open-label, multicenter, interventional study in racially self-identified black or ethnically self-identified hispanic and racially self-identified white or native American participants with metastatic castration-resistant prostate cancer whose tumors demonstrate molecular alterations compatible with homologous repair deficiency.

Study Overview

• Status: Withdrawn
• Conditions: Prostate Cancer; Homologous Recombination Deficiency; Castrate Resistant Prostate Cancer
• Intervention / Treatment: Drug: Niraparib/Abirate rone acetate fixed-dose combination; Drug: Prednisone

Detailed Description

This study will enroll up to 70 participants, divided into two cohorts of 35 each. Cohort A will include participants self-identified as of black origin, as defined by the FDA Guidance on Collection of Race and Ethnicity Data in Clinical Trials, including those with more than one race, such as pardos. Cohort B will include (1) participants self-identified from Native Indigenous American origins and (2) participants self-identified from White origin who ethnically identify as Latinos, both as per the FDA guidance. The study will consist of five phases: Prescreening for biomarker evaluation, Screening, Treatment, Extension, and Follow-Up. Participants will be assessed during prescreening using the sponsor's required assays or previous results from CLIA-certified labs showing a pathogenic germline or somatic HRR alteration.

The combination of niraparib/AA plus prednisone is FDA-approved for treating homologous repair deficient metastatic castration-resistant prostate cancer (HRD mCRPC). Given the benefits of this combination and the lack of representation in previous studies, a placebo-controlled study is deemed unethical. Thus, the study design includes two independent cohorts, both receiving the standard of care treatment. This study aims to provide additional information on the benefits of this therapy in underrepresented populations. Conducted with input from experts in racial inequities, the study results may be shared with participants through a plain language summary. Participants will be fully informed about the study's risks and requirements and will receive new information affecting their participation decision. Consent to participate is voluntary and can be withdrawn at any time without penalty. Written consent will be obtained following regulations and participant preferences.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Eligibility criteria - Prescreening Inclusion

Age:

≥18 years of age (or the local legal age of consent)

Participant Origin:

Participants of the following origins:

- COHORT A: Participants self-identified as with black origin as defined as having origins in any of the black racial groups of Africa, as per the FDA Guidance on Collection of Race and Ethnicity Data in Clinical Trials, and irrespective of ethnicity. This includes participants with more than one race, including pardos.

- COHORT B: Participants self-identified from Native Indigenous American origins as per the FDA Guidance on Collection of Race and Ethnicity Data in Clinical Trials, irrespective of ethnicity. This includes participants with more than one race, including mestizos.

OR

- Participants self-identified from White origin as per the FDA Guidance on Collection of Race and Ethnicity Data in Clinical Trials, and ethnically self-identified as Latinos.

Participant and Disease Characteristics

• ECOG Performance Status 0-1
• Histologically or cytologically confirmed metastatic prostate adenocarcinoma

• Metastatic disease documented by conventional imaging with CT or MRI (for soft tissue lesions) or 99mTc bone scan (for bone lesions)

  1. Participants with a single bone lesion on 99mTc bone scan with no other non-nodal metastatic disease must have confirmation of bone metastasis by CT or MRI.
  2. Participants with lymph node-only disease are not eligible.

• Willing to provide tumor tissue (archival) for determination of deleterious germline or somatic HRR gene alterations, if no local (testing done at investigator center or commercial testing) or prior sponsor-approved test result is available.

  1.Testing must demonstrate pathogenic gene alterations in ≥1 of the following genes to proceed to screening: ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, or PALB2.

• Castration-resistant disease, defined by the PCWG3 as any of the following criteria while on castrate levels of testosterone (less than or equal to 50 ng/dL):

  1. Visceral Progression OR
  2. Bone progression (2 or more new prostate-cancer related new lesions compared to baseline) OR

  3. PSA Progression, as defined by an increase in two consecutive measurements that fulfills all the following criteria:

     1. The evaluations were performed with a minimum interval of 1 week.
     2. Progressive worsening with an increase of at least 50% compared to baseline.
     3. The minimum value of PSA is ≥ 1 ng/ml.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: self-identified as from Black racial origin irrespective of ethnicity; Cohort A will include participants self-identified as from Black origin as defined as having origins in any of the Black racial groups of Africa, as per the FDA Guidance on Collection of Race and Ethnicity Data in Clinical Trials, and irrespective of ethnicity. This includes participants with more than one race, including pardos.	Drug: Niraparib/Abirate rone acetate fixed-dose combination; Participants will receive niraparib/abiraterone acetate fixed-dose combination 100/500 mg 2 tablets once daily on days 1-28 of each 28-day cycle.; Drug: Prednisone; Participants will receive prednisone 5mg 2 tablets once daily on days 1-28 of each 28-day cycle.
Experimental: Racially self-identified as Native Indigenous American or self-identified Latino and racially White; Cohort B will include participants of the following racial and ethnic backgrounds: self-identified as from Native Indigenous American origins as per the FDA Guidance on Collection of Race and Ethnicity Data in Clinical Trials, irrespective of ethnicity (this includes participants with more than one race, including mestizos); self-identified as from White origin as per the FDA Guidance on Collection of Race and Ethnicity Data in Clinical Trials, and ethnically self-identified as Latinos. This includes participants with mixed (or mestizo) races.	Drug: Niraparib/Abirate rone acetate fixed-dose combination; Participants will receive niraparib/abiraterone acetate fixed-dose combination 100/500 mg 2 tablets once daily on days 1-28 of each 28-day cycle.; Drug: Prednisone; Participants will receive prednisone 5mg 2 tablets once daily on days 1-28 of each 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month radiographic Progression-Free Survival (rPFS)	Assessed by modified RECIST v1.1 and PCWG3 criteria, and defined as time from enrollment until progression of soft tissue lesions measured by CT or MRI as defined in RECIST 1.1, progression of bone lesions observed by bone scan and based on PCWG3, or death from any cause.	12 months

Collaborators and Investigators

• Sponsor: Latin American Cooperative Oncology Group
• Collaborators: Janssen, LP
• Investigators: Principal Investigator: Fernando Cotait Maluf, Latin American Cooperative Oncology Group

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: July 25, 2024
• First Submitted That Met QC Criteria: July 25, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Prednisone; niraparib
• Other Study ID Numbers: LACOG 1223; 67652000PCR2006 (Other Grant/Funding Number: Janssen)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No