Metastatic castration-resistant prostate cancer (mCRPC) MedDRA version: 20.0 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Subjects of age 18 years or older 2. Willing to undergo all protocol-specified biopsies 3. Diagnosis of prostate adenocarcinoma as confirmed by the investigator. 4. Must have determination of biomarker status (either biomarker-positive [BM+] or biomarker–negative [BM-] by the sponsor’s blood-based assay 5. Subjects must have measurable disease as defined by RECIST 1.1 (soft tissue lesion of =10mm in the long axis or extrapelvic lymph node of =15mm in the short axis). 6. Must have previously received at least 1, but no more than 2, lines of novel AR-targeted therapy (eg, abiraterone acetate with prednisone, enzalutamide, apalutamide) for prostate cancer. Subjects must have had at least 4 weeks of AR-targeted therapy 7. Must have castrate levels of testosterone =50 ng/dL on a gonadotropin releasing hormone analogue (GnRHa), or history of bilateral orchiectomy at study entry 8. Progression of metastatic prostate cancer at study entry defined as having one or more of the following: a. PSA progression defined by a minimum of 2 rising PSA levels with an interval of =1 week between each determination (per Prostate Cancer Working Group 3 [PCWG3] criteria). The PSA level at the screening visit should be =2 µg/L (2 ng/mL). b. Radiographic progression by bone scan per PCWG3 or by soft tissue per RECIST 1.1. 9. Must be willing to continue GnRHa during the study if not surgically castrate. 10. Eastern Cooperative Oncology Group Performance Score (ECOG PS) Grade of 0 or 1 11. Subjects who received prior therapy with an anti-androgen (eg, bicalutamide, flutamide, nilutamide, abiraterone acetate with prednisone, enzalutamide, apalutamide) must have at least a 4-week washout prior to enrollment. 12. To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must agree while on study drugs and for 5 months following the last dose of study drugs to: a.Use a condom during sexual activity. b.Not donate sperm. 13. Clinical laboratory values at Screening: a.Absolute neutrophil count (ANC) =1.5 x 10^9/L, independent of growth factors for 30 days b.Hemoglobin =9.0 g/dL, independent of growth factors or transfusions for 30 days c.Platelet count =100 x 10^9/L, independent of growth factors or transfusions for 30 days d.Serum albumin =3.0 g/dL e.Creatinine clearance =30 mL/min/1.73 m^2 either calculated or directly measured via 24-hour urine collection f.Serum total bilirubin =1.5 x upper limit of normal (ULN) or direct bilirubin =1 x ULN (Note: in subjects with Gilbert’s syndrome, if total bilirubin is >1.5 x ULN, measure direct and indirect bilirubin, and if direct bilirubin is =1.5 x ULN, subject may be eligible as determined by the medical monitor) g.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =3 x ULN h.Fasting glucose =250 mg/dL Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 28 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: 1. Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor. 2. History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). 3. Active malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently remission) =2 years prior to enrollment. 4. Active infection requiring systemic therapy. 5. Allergies, hypersensitivity, or intolerance to niraparib or the corresponding excipients (refer to the Investigator’s Brochures). 6. Human immunodeficiency virus (HIV)-positive subjects with 1 or more of the following: a. Not receiving highly active antiretroviral therapy. b. A change in antiretroviral therapy within 6 months of the start of screening (except if, after consultation with the sponsor on exclusion criterion 11.c, a change is made to avoid a potential drug-drug interaction with the study drug). c. Receiving antiretroviral therapy that may interfere with the study drug (consult the sponsor for review of medication prior to enrollment). d. CD4 count <350 cells/mm^3 at screening. e. An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening. 7. Active hepatitis B virus (eg, hepatitis B surface antigen reactive) or active hepatitis C virus (HCV) (eg, HCV ribonucleic acid [RNA] [qualitative] is detected). 8. If a subject has undergone major surgery, they must have recovered adequately from the toxicities or complications from the intervention prior to starting therapy. 9. Prior radium treatment or treatment with other therapeutic radiopharmaceuticals for prostate cancer. 10. Any of the following =30 days prior to planned Cycle 1 Day 1: a.A transfusion (platelets or red blood cells). b.Hematopoietic growth factors. c.An investigational agent for prostate cancer. d.Major surgery (sponsor's medical monitor should be consulted regarding what constitutes major surgery). e.Radiation therapy 11. Symptomatic brain metastasis from prostate cancer. 12. Symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease), unstable angina pectoris, cardiac arrhythmia, or uncontrolled hypertension. 13. Any condition for which, in the opinion of the investigator or medical monitor, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. For excl.criteria to combination 1: Niraparib and JNJ63723283: 1. Prior treatment with sipuleucel-T. 2. Prior therapy with an anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody (including any antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 3. Subjects with a history of allergy to protein-based therapies or any significant drug allergy (ie, analphylaxis, heptatotoxicity, or immune-mediated thrombocytopenia or anemia). 4. History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis. 5. Allergies, hypersensitivity, or intolerance to JNJ-63723283 or the corresponding excipients (refer to the Investigator’s Brochure). 6. Immunodeficiency or receiving systemic corticosteroid therapy or immunosuppressive therapy (eg, cyclosporine) within 7 days prior to treatment allocation. The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor. 7.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: - To evaluate the tolerability of niraparib combination therapies for the treatment of mCRPC - Determine the recommended Phase 2 dose (RP2D) of niraparib combination therapies Part 2 (Dose Expansion): - To evaluate the antitumor effect of the RP2D of niraparib combination therapies for treatment of mCRPC - To evaluate the safety of the RP2D of niraparib combination therapies for the treatment of mCRPC;Secondary Objective: Part 1: - To characterize the pharmacokinetics (PK) and immunogenicity (if applicable) of niraparib combination therapies Part 2: - To evaluate other response outcomes of niraparib combination therapies for the treatment of mCRPC - To evaluate duration of response - To characterize the PK and immunogenicity (if applicable) of niraparib combination therapies through sparse sampling;Primary end point(s): Part 1: 1. Incidence of specified toxicities Part 2: 2. Objective response rate (ORR) of soft tissue (visceral or nodal disease) 3. Incidence and severity of Adverse events (AEs);Timepoint(s) of evaluation of this end point: 1. First 28 days of treatment (Cycle 1) 2. From Cycle (C) 1 Day (D) 1, imaging will be performed every 8 weeks for the first 6 months and then every 12 weeks thereafter 3. Day 0 to until the End-of-treatment (EOT) visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: 1. Plasma concentrations of niraparib and, if performed, its major metabolite (M1), and plasma or serum concentrations of the combination agent 2. Population PK parameters and derived exposure of niraparib and combination agent 3. Anti-drug antibodies (if applicable) Part 2: 4. Circulating tumor cell (CTC) response 5. Response rate (RR) 6. Duration of objective response 7. Overall survival (OS) 8. Plasma concentrations of niraparib and, if performed, its major metabolite (M1) when dosed with combination agent 9. Population PK parameters and derived exposure of niraparib and combination agent 10. Anti-drug antibodies (if applicable);Timepoint(s) of evaluation of this end point: 1, 2, 8 and 9. Cycle (C) 1 Day (D) 1, C2 D1, C3 D1, C6 D1 and C12 D1 3 and 10. Cycle 1 (D1, 15), C2 (D1, 15), C3 (D1, 15), C4 (D1, 15), C5 (D1, 15), C6 (D1, 15), C7 (D1, 15), C9 D1, C10 D1, C12 (D1, 15), at end of treatment (EoT) visit and follow-up 4. At every cycle from C 1 D 1 through C 12 D 1, and at the EoT visit 5, 6 and 7. Day 1 to until death | — |
Countries
Canada, Israel, Spain, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Operations Spain
Janssen-Cilag International N.V.
Outcome results
None listed