Niraparib, Abiraterone Acetate and Prednisone for mHSPC With Deleterious Homologous Recombination Repair Alterations

NCT06392841 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HCRN-GU23-626
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open label, phase II trial in subjects with treatment naïve, metastatic hormone sensitive prostate cancer (mHSPC) with deleterious homologous recombination repair (HRR) alteration(s). These include pathologic alterations in BRCA 1/2, BRIP1, CHEK2, FANCA, PALB2, RAD51B, and/or RAD54L. A total of 64 people will be enrolled to the study.

Conditions

Deleterious HRR Gene Mutation; BRCA2 Gene Mutation; BRIP1 Gene Mutation; PALB2 Gene Mutation; RAD51B Gene Mutation; RAD54L Gene Mutation; BRCA1 Gene Mutation; CHEK2 Gene Mutation; FANCA Gene Mutation; Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

Outcome Measures

Primary Outcomes (1)

• Rate of participants with PSA decline to < 0.2 ng/ml

  PSA decline is defined as percentage of participants with PSA decline to \< 0.2 ng/ml at 24 weeks of therapy with ADT and niraparib/abiraterone acetate DAT plus prednisone as determined by Cycle 7 Day 1 PSA

  24 weeks

Secondary Outcomes (8)

• Rate of participants with PSA reduction ≥ 90% (PSA90)

  24 weeks

• Percentage of participants with PSA decline to < 0.2 ng/ml (Cohort A)

  12 months

• Percentage of participants with PSA decline to < 0.2 ng/ml (Cohort B)

  12 months

• Overall response rate (ORR)

  4 years

• PSA progression free survival (PFS)

  4 years

Study Arms (3)

Initial Treatment (Cycle 1 to Cycle 6)

EXPERIMENTAL

Androgen Deprivation Therapy (ADT) with a GnRH agonist or antagonist per standard of care. 200 mg niraparib and 1,000 mg abiraterone acetate dual action tablet (DAT, Akeega) once daily, with 5mg prednisone once daily for 24 weeks (6 cycles) unless there is progression or unacceptable toxicity. After 6 cycles, disease evaluation performed.

Drug: Androgen Deprivation Therapy (ADT); Drug: Niraparib/Abiraterone Acetate DAT; Drug: Prednisone

Cohort A: prostate specific antigen (PSA) >4 ng/mL without progression at the completion of 24 weeks

EXPERIMENTAL

After 6 cycles, there will be an option to: 1. Continue ADT + niraparib/abiraterone acetate plus prednisone in 28-day cycles for a total of 2 years OR until disease progression or unacceptable toxicity. Subsequent therapy will be at the discretion of the investigator per standard of care. 2. Discontinue niraparib. Continue ADT, start abiraterone acetate plus prednisone and docetaxel 75mg/m2 in 21-day cycles. Docetaxel every 3 weeks x 6 doses. At the completion of docetaxel, the subject will move to follow-up per protocol. Niraparib should not be restarted at the completion of docetaxel. Subsequent therapy will be at the discretion of the investigator per standard of care.

Drug: Androgen Deprivation Therapy (ADT); Drug: Niraparib/Abiraterone Acetate DAT; Drug: Abiraterone Acetate; Drug: Prednisone; Drug: Docetaxel

Cohort B: PSA ≤ 4 ng/mL without progression at the completion of 24 weeks

EXPERIMENTAL

Continue ADT + niraparib/abiraterone acetate plus prednisone for 1 year unless progression or unacceptable toxicity. At 1 year, disease evaluation will occur. * PSA ≥ 0.2 ng/mL: ADT + niraparib/abiraterone acetate plus prednisone will continue for 2 years or until progression or unacceptable toxicity. Therapy beyond 2 years will be per standard of care per investigator discretion. * PSA \< 0.2 ng/mL and PSA not trending up: 1. Continue ADT + niraparib/abiraterone acetate plus prednisone for 2 years or until progression or unacceptable toxicity. Therapy beyond 2 years will be per standard of care per investigator discretion OR 2. STOP ADT + niraparib/abiraterone acetate plus prednisone only IF: * C14 PSA \< 0.2 AND not trending up * Subjects not eligible that elect to stop ADT + niraparib/abiraterone acetate plus prednisone, will be removed from protocol treatment and move to follow-up. Subsequent therapy re-initiation will be at the discretion per standard of care.

Drug: Androgen Deprivation Therapy (ADT); Drug: Niraparib/Abiraterone Acetate DAT; Drug: Prednisone

Interventions

Docetaxel DRUG

75 mg/m2 IV

Also known as: Docefrez, Taxotere

Cohort A: prostate specific antigen (PSA) >4 ng/mL without progression at the completion of 24 weeks

Androgen Deprivation Therapy (ADT) DRUG

Medical castration per ADT with GnRH agonist or antagonist (or surgical castration per orchiectomy)

Cohort A: prostate specific antigen (PSA) >4 ng/mL without progression at the completion of 24 weeks; Cohort B: PSA ≤ 4 ng/mL without progression at the completion of 24 weeks; Initial Treatment (Cycle 1 to Cycle 6)

Niraparib/Abiraterone Acetate DAT DRUG

Niraparib 200 mg/ Abiraterone acetate 1000 mg orally

Also known as: Akeega

Cohort A: prostate specific antigen (PSA) >4 ng/mL without progression at the completion of 24 weeks; Cohort B: PSA ≤ 4 ng/mL without progression at the completion of 24 weeks; Initial Treatment (Cycle 1 to Cycle 6)

Abiraterone Acetate DRUG

1000 mg orally

Also known as: Zytiga

Cohort A: prostate specific antigen (PSA) >4 ng/mL without progression at the completion of 24 weeks

Prednisone DRUG

5 mg orally

Also known as: Rayos, Deltasone, Prednisone Intensol

Cohort A: prostate specific antigen (PSA) >4 ng/mL without progression at the completion of 24 weeks; Cohort B: PSA ≤ 4 ng/mL without progression at the completion of 24 weeks; Initial Treatment (Cycle 1 to Cycle 6)

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• ≥ 18 years of age at the time of consent.
• Self-identify as Hispanic/Latino or non-Hispanic black racial/ethnic background.
• ECOG Performance Status of ≤ 2 within 30 days prior to registration.
• Histologically confirmed diagnosis of prostate adenocarcinoma.
• Deleterious HRR alteration(s) per any validated test, next generation sequencing (NGS) mutational analysis (tissue or liquid). These include BRCA 1/2, BRIP1, CHEK2, FANCA, PALB2, RAD51B, and/or RAD54L.
• Radiographic evidence of metastatic disease as per conventional CT or MRI of chest, abdomen pelvis and bone scan, according to RECIST version 1.1 criteria in subjects with measurable disease and PCWG3 criteria for subjects with bone only disease (1, 2). Evidence of metastatic disease detected on Axumin or PSMA PET/CT will need confirmation on conventional CT or MRI/bone scans.
• Hormone sensitive, treatment naïve/minimally treated \[first generation androgen receptor inhibitor (ARI) such as bicalutamide ≤ 45 days, ADT ± abiraterone acetate plus prednisone ≤ 45 days allowed\]. Prior therapy for localized prostate cancer allowed (including but not limited to radiation therapy, prostatectomy, lymph node dissection ± ADT, must have been completed \> 6 months prior to registration).
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 30 days prior to registration.
• Platelets (Plt): ≥ 100 x 10\^9/L (Independent of transfusions for at least 28 days prior to registration)
• Absolute Neutrophil Count (ANC): ≥ 1.5 x 10\^9/L (Independent of hematopoietic growth factors for at least 28 days prior to registration)
• Hemoglobin (Hgb): ≥ 9 g/dL (Independent of transfusions for at least 28 days prior to registration)
• Creatinine: Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min
• Total bilirubin: ≤ 1.5 × ULN or direct bilirubin ≤ 1 x ULN (For 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, subjects may be eligible.)
• Aspartate aminotransferase (AST): ≤ 3 × ULN

You may not qualify if:

• Prostate cancer variants including predominant neuroendocrine features and/or predominant small cell carcinoma of the prostate are excluded.
• Prior treatment with the following is excluded: second generation ARIs such as apalutamide, enzalutamide, darolutamide, or other investigational ARIs; oral ketoconazole as antineoplastic treatment for prostate cancer (allowed if total time on ketoconazole as prostate cancer-directed therapy is ≤ 10 days and discontinued prior to study treatment initiation); chemotherapy or immunotherapy for prostate cancer.
• Radiotherapy/radiopharmaceuticals within 2 weeks of registration.
• History of severe allergic anaphylactic reactions to niraparib/abiraterone acetate tablets or any of their excipients.
• Current evidence of any medical condition that would make prednisone use contraindicated.
• Long-term use of systemically administered corticosteroids (\> 5mg of prednisone or the equivalent) during the study is not allowed (5mg of prednisone or equivalent daily, given with abiraterone acetate, is allowed). Short-term use of corticosteroid for indication other than in combination with abiraterone acetate (≤ 4 weeks, including taper) and locally administered steroids (eg, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated.
• Subjects who have had major surgery ≤ 28 days prior to registration.
• Symptomatic brain metastases.
• Active or symptomatic viral hepatitis or chronic liver disease; encephalopathy, ascites, or bleeding disorders secondary to hepatic dysfunction.
• Moderate or severe hepatic impairment (Class B and C per Child-Pugh classification system.
• History of adrenal insufficiency not adequately managed.
• History or current diagnosis of MDS/AML.
• Current evidence within 6 months prior to registration of any of the following:
• Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure,
• Clinically significant arterial or venous thromboembolic events (ie. pulmonary embolism), or clinically significant ventricular arrhythmias.

Sponsors & Collaborators

• UT Southwestern Comprehensive Cancer Center: collaborator
• Qian Qin: lead
• Janssen, LP: collaborator

MeSH Terms

Interventions

Androgen Antagonists; niraparib; Abiraterone Acetate; Prednisone; Docetaxel

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Qian Qin, MD

  UT Southwestern Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

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: Assistant Professor

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: April 30, 2024
• Study Start: October 1, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share