Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: niraparib/abiraterone 50/500mg(G009)
Product Code: CJNJ-67652000-G009
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: NIRAPARIB
CAS Number: 1038915-60-4
Current Sponsor code
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. 18 years of age or older 2. Diagnosis of prostate adenocarcinoma. 3. Willing to provide an archival tumor tissue sample or a fresh tumor tissue sample. If germline positive for deleterious germline or somatic HRR gene mutations, an archived or fresh tumor tissue sample is not required. 4. Metastatic disease documented by =1 bone lesion(s) on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by CT or MRI. 5 Must have at least one of the deleterious germline or somatic HRR gene mutations listed in Table 4. 6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade 14 days prior to randomization and willing to continue through the treatment phase. Participants who start a GnRH agonist 14 days prior to randomization. The anti-androgen must be discontinued prior to randomization. 8. Participants who have received prior docetaxel treatment must meet the following criteria: a. Received a maximum of 6 cycles of docetaxel therapy for mCSPC b. Received the last dose of docetaxel 1.5 × ULN, measure direct and indirect bilirubin, and if direct bilirubin is =1.5 × ULN, participant may be eligible as determined by the medical monitor) h. AST or ALT =3 × ULN 12. Able to swallow the study medication tablets whole. 13. Must provide informed consent (written or remote/virtual) indicating that he understands the purpose of, and procedures required for, the study and is willing to participate in the study including providing a DNA sample. 14. While on study medication and for 3 months following the last dose of study medication, a male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak. The investigator should advise of the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study medication.
Exclusion criteria
Exclusion criteria: 1. Pathological finding consistent with small cell ductal or neuroendocrine carcinoma of the prostate. 2. Prior treatment with a PARP inhibitor. 3.Prior AR-targeted therapy (eg, ketoconazole for prostate cancer, apalutamide, enzalutamide, darolutamide), immunotherapy, or radiopharmaceutical agents with the exception of only 30 days of AA-P allowed prior to randomization. 4. Initiation of treatment with a bisphosphonate or denosumab for the management of bone metastasis 5 mg of prednisone or the equivalent) during the study is not allowed. Short-term use (=4 weeks, including taper) and locally administered steroids (eg, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated. 7. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: a. non-muscle invasive bladder cancer; b. skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured; c. breast cancer – adequately treated lobular carcinoma in situ or ductal carcinoma in situ; d. malignancy that is considered cured with minimal risk of recurrence. 8. History or current diagnosis of MDS/AML. 9. Current evidence within 6 months prior to randomization of any of the following: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, clinically significant arterial or venous thromboembolic events (eg, pulmonary embolism), or clinically significant ventricular arrhythmias. 10. Presence of sustained uncontrolled hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg). Participants with a history of hypertension are allowed, provided that blood pressure is controlled to within these limits by an antihypertensive treatment. 11. Known allergies, hypersensitivity, or intolerance to the excipients of niraparib, AA, or niraparib/AA FDC (refer to the IBs for niraparib and AA). 12. Current evidence of any medical condition that would make prednisone use contraindicated. 13. Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the planned first dose of study medication. 14. Participants who have had the following =28 days prior to randomization: a. A transfusion (platelets or red blood cells); b. Hematopoietic growth factors; c. Major surgery (sponsor should be consulted regarding what constitutes major surgery). 15. Known active hepatitis B virus (eg, hepatitis B surface antigen reactive) or active hepatitis C virus (HCV; eg, HCV ribonucleic acid [RNA] [qualitative] is detected). 16. Human immunodeficiency virus positive participants with 1 or more of the following: a. Not receiving highly active antiretroviral therapy or on antiretroviral therapy for less than 4 weeks. b. Receiving antiretroviral therapy that may interfere with the study medication (consult the sponsor for review of medication prior to enrollment). c. A change in antiretroviral therapy within 6 months of the start of screening (except if, after consultation with the sponsor on exclusion criterion 16.b, a change is made to avoid a potential drug-drug interaction with the study medication). d. CD4 count <350 at screening. e. An a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if niraparib, AA, and prednisone compared with AA and prednisone in participants with deleterious germline or somatic HRR gene-mutated mCSPC provides superior efficacy in improving rPFS;Secondary Objective: - To assess the clinical benefit of niraparib, AA, and prednisone compared with AA and prednisone in participants with deleterious germline or somatic HRR gene-mutated mCSPC - To characterize the safety profile of niraparib, AA, and prednisone compared with AA and prednisone in participants with deleterious germline or somatic HRR gene-mutated mCSPC;Primary end point(s): Radiographic progression-free survival (rPFS) ;Timepoint(s) of evaluation of this end point: While on study treatment, radiographic imaging will be performed every 8 weeks for the first 6 months and every 12 weeks thereafter | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): * OS * Symptomatic progression-free survival * Time to subsequent therapy ;Timepoint(s) of evaluation of this end point: Assessments of the secondary endpoints are variable but carried out on a regular basis throughout study as described in the endpoint requirements | — |
Countries
Argentina, Australia, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Moldova, Republic of, Netherlands, New Zealand, Poland, Portugal, Russian Federation, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Registry group
Janssen-Cilag International N.V.
Outcome results
None listed