A Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Sponsor: Janssen Research & Development, LLC
ClinicalTrials ID:NCT03431350
This multicenter study assesses the safety and efficacy of niraparib with cetrelimab or abiraterone acetate plus prednisone in mCRPC patients. It includes dose selection, expansion, and bioavailability phases. Participants receive niraparib, cetrelimab, abiraterone acetate, and prednisone. Evaluations cover efficacy, pharmacokinetics, biomarkers, safety, and tolerability.
Patient Parameters
| Parameter | Options |
|---|
Program Overview
The purpose of this study is to: a) establish the recommended phase 2 dose (RP2D) and to evaluate the antitumor activity and safety of niraparib combination therapies (Combinations 1 and 2) and b) to determine the relative bioavailability of niraparib and abiraterone acetate (AA) in combination (Combination 3) in participants with metastatic castration-resistant prostate cancer (mCRPC).
Description
This multicenter study will evaluate safety and efficacy of niraparib in combination with other anti-cancer agents. Combination 1 will combine niraparib with the anti-programmed cell death protein (PD)-1 monoclonal antibody cetrelimab, in participants with mCRPC. Combination 1 has 2 parts: in Part 1 (dose selection), participants will be enrolled to establish RP2D doses of niraparib and cetrelimab; and Part 2 (dose expansion) will evaluate the combination therapy in an expanded number of participants into 2 cohorts (biomarker positive or biomarker negative). Combination 2 will combine niraparib with abiraterone acetate plus prednisone (AA-P) in mCRPC participants with DNA-repair gene defects (DRD). Combination 3 will evaluate the relative bioavailability (BA) of niraparib and AA in combination. In a pharmacokinetics (PK) assessment phase, niraparib and AA will be administered, and in an extension phase, niraparib and AA-P will be administered. Combinations 1 and 2 will have 5 phases: A Pre-screening Phase, a Screening Phase, a Treatment Phase, a Follow-up Phase, and a Long-term Extension (LTE) Phase; Combination 3 has 3 phases: A Screening Phase, A PK Assessment Phase, an Extension Phase (including LTE phase). Study evaluations will include efficacy, PK, PK/pharmacodynamics, biomarkers, safety and tolerability.
Eligibility Criteria
Exclusion Criteria
- History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
- Active malignancies (that is, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: non-muscle invasive bladder cancer; skin cancer (non-melanoma or melanoma); breast cancer; malignancy that is considered cured with minimal risk of recurrence
- Active infection requiring systemic therapy
- Allergies, hypersensitivity, or intolerance to niraparib or the corresponding excipients
Combination 3:
- Symptomatic brain metastases
- Prior disease progression during combination treatment with AA and poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor (PARPi). Prior discontinuation of treatment with AA or PARPi due to AA- or PARPi-related toxicity
Locations
| FACILITY | ZIP | CITY | STATE |
|---|---|---|---|
| Urological Associates of Southern Arizona, P.C. | 85741 | Tucson | Arizona |
| The Urology Center of Colorado | 80211 | Denver | Colorado |
| Mayo Clinic - Division Of Hematology/oncology | 32224 | Jacksonville | Florida |
| First Urology, PSC | 47130 | Jeffersonville | Indiana |
| Chesapeake Urology Research Associates | 21204 | Towson | Maryland |
| Michigan Institute of Urology | 48084 | Troy | Michigan |
| New York Oncology Hematology | 12208 | Albany | New York |
| Memorial Sloan Kettering Cancer Center | 10604 | Harrison | New York |
| Memorial Sloan Kettering Cancer Center | 10065 | New York | New York |
| Thomas Jefferson University | 19107 | Philadelphia | Pennsylvania |
Get This Program In Your Inbox
You can sign up and apply your patients for this program.