Phase 2 Study of CJNJ-67652000 (Niraparib/Abiraterone Acetate Fixed-Dose Combination) and Prednisone for Metastatic Castration-Resistant Prostate Cancer Associated With SPOP Mutation With or Without Homologous Recombination Deficiency
Overview
- Phase
- Phase 2
- Intervention
- Biospecimen Collection
- Conditions
- Not specified
- Sponsor
- Mayo Clinic
- Enrollment
- 8
- Locations
- 3
- Primary Endpoint
- Prostate specific antigen (PSA) response rate (PSA decline by >= 50% [PSA50])
- Status
- Active, not recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
This phase II trial tests how well abiraterone acetate/niraparib (CJNJ-67652000 [niraparib/abiraterone acetate fixed-dose combination]) and prednisone works in treating patients with castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and who have a mutation in the SPOP gene. CJNJ-67652000 (niraparib/abiraterone acetate fixed-dose combination) is a drug which stops certain cancer cells from being able to repair themselves from damage, leading to the death of the cancer cell. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving CJNJ-67652000 and prednisone may kill more tumor cells in patients with metastatic prostate cancer than giving these drugs alone.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the efficacy of abiraterone acetate/niraparib (CJNJ-67652000 \[niraparib/abiraterone acetate fixed-dose combination\]) and prednisone as assessed by prostate-specific antigen decline \>= 50% (PSA50) response rate in patients with metastatic castrate-resistant prostate cancer (mCRPC) who have failed prior treatment with androgen receptor (AR)-targeted therapy and have a qualifying, deleterious SPOP mutation. SECONDARY OBJECTIVES: I. To assess the radiologic progression free survival (rPFS) of CJNJ-67652000 (niraparib/abiraterone acetate fixed-dose combination) and prednisone treatment in patients with mCRPC who have failed prior treatment with AR-targeted therapy and have a qualifying, deleterious SPOP mutation. II. To assess best radiographic response using Prostate Cancer Working Group 3 (PCWG3) criteria. III. To assess time to prostate specific antigen (PSA) progression. IV. To assess safety and tolerability using National Cancer Institute (NCI) Common Toxicity Criteria Version 5.0. CORRELATIVE RESEARCH OBJECTIVES: I. To explore the landscape of genomic alterations occurring after use of CJNJ-67652000 (niraparib/abiraterone acetate fixed-dose combination) and prednisone. II. To use blood, tissue, or organoid lines for identifying predictive biomarkers of response, investigating drug resistance mechanisms, and for future drug efficacy studies. III. To explore the relationship of other genomic alterations in the tumor tissue with overall response rate (ORR) and disease progression. OUTLINE: Patients receive CJNJ-67652000 orally (PO) and prednisone PO on study. Patients also undergo blood specimen collection, computed tomography (CT) or magnetic resonance imaging (MRI), and bone scan throughout the trial.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male \>= 18 years of age
- •Histological confirmation of adenocarcinoma of the prostate
- •Qualifying deleterious SPOP mutation detected on any archival genomic assay (tissue and/or liquid biopsy) is acceptable for study inclusion. Qualifying mutation(s) of SPOP include any genomic change predicted to be deleterious or suspected deleterious. SPOP status must be established prior to involvement on the trial
- •Evidence of metastatic castration-resistant prostate cancer, defined as at least one (1) documented metastatic lesion on either bone scan or CT scan. Bone only disease is acceptable for enrollment. Non-bone metastatic lesions must be measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Subjects whose disease spread is limited to regional pelvic lymph nodes or local recurrence (e.g. bladder, rectum) are not eligible
- •Radiographic or PSA progression while on androgen deprivation therapy (or after bilateral orchiectomy) AND at least one prior AR-targeted therapy (abiraterone acetate, enzalutamide, apalutamide, darolutamide or investigational AR-targeted agents). PSA progression is a PSA increase that is \>= 25% and \>= 2 ng/mL above the nadir, and which is confirmed by a second value (minimum 1 week interval between tests). For radiographic progression of soft tissue lesions, modified RECIST 1.1 criteria will be used to qualify entry. For radiographic progression of bony disease, two new lesions must be seen as per PCWG3 criteria. No confirmatory scan of bone progression is required prior to study entry
- •A maximum of two lines of prior taxane (docetaxel and/or cabazitaxel) chemotherapy will be allowed, but are not required
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- •Surgically or medically castrated, with serum testosterone levels of =\< 50 ng/dL (1.73 nM). For patients currently being treated with luteinizing hormone-releasing hormone (LHRH) analogs (ie, patients who have not undergone an orchiectomy), therapy must be continued throughout the study
- •Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within 14 days prior to registration)
- •Platelet count \>= 100,000/mm\^3 (within 14 days prior to registration)
Exclusion Criteria
- •Prior treatment with PARP inhibitor or platinum chemotherapy
- •Historical or current diagnosis of myelodysplastic syndrome or myeloid malignancy
- •Any of the following prior therapies:
- •Surgery =\< 3 weeks prior to registration
- •Chemotherapy =\< 2 weeks prior to registration
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •Clinician assessed prognosis of less than 16 weeks
- •Human immunodeficiency virus (HIV) positive subjects with 1 or more of the following:
- •Not receiving highly active antiretroviral therapy
- •Receiving antiretroviral therapy that may interfere with the study drug (consult the sponsor for review of medication prior to enrollment)
Arms & Interventions
Treatment (CJNJ-67652000 and prednisone)
Patients receive CJNJ-67652000 PO and prednisone PO on study. Patients also undergo blood specimen collection, CT or MRI, and bone scan throughout the trial.
Intervention: Biospecimen Collection
Treatment (CJNJ-67652000 and prednisone)
Patients receive CJNJ-67652000 PO and prednisone PO on study. Patients also undergo blood specimen collection, CT or MRI, and bone scan throughout the trial.
Intervention: Abiraterone Acetate/Niraparib
Treatment (CJNJ-67652000 and prednisone)
Patients receive CJNJ-67652000 PO and prednisone PO on study. Patients also undergo blood specimen collection, CT or MRI, and bone scan throughout the trial.
Intervention: Bone Scan
Treatment (CJNJ-67652000 and prednisone)
Patients receive CJNJ-67652000 PO and prednisone PO on study. Patients also undergo blood specimen collection, CT or MRI, and bone scan throughout the trial.
Intervention: Computed Tomography
Treatment (CJNJ-67652000 and prednisone)
Patients receive CJNJ-67652000 PO and prednisone PO on study. Patients also undergo blood specimen collection, CT or MRI, and bone scan throughout the trial.
Intervention: Magnetic Resonance Imaging
Treatment (CJNJ-67652000 and prednisone)
Patients receive CJNJ-67652000 PO and prednisone PO on study. Patients also undergo blood specimen collection, CT or MRI, and bone scan throughout the trial.
Intervention: Prednisone
Outcomes
Primary Outcomes
Prostate specific antigen (PSA) response rate (PSA decline by >= 50% [PSA50])
Time Frame: Baseline to end of treatment (approximately 13 months)
PSA50 response rate is defined as \> 50% PSA decrease as compared to baseline. The proportion of PSA responses will be estimated by the number of PSA responses divided by the total number of evaluable patients. 95% exact binomial confidence intervals will be computed. The frequency and relative frequency of individual PSA response categories will also be computed. In addition, the maximum percentage change for PSA will be computed and displayed graphically via waterfall plots for individual patients.
Secondary Outcomes
- Time to progression(Up to 2 years)
- Radiologic progression-free survival (rPFS)(Up to 2 years)
- Incidence of adverse events(Up to 30 days after last treatment dose)