prostate cancer
Conditions
Interventions
there will be 4 different groups:
1.
Period 1: 100mg Niraparib/1000mg Abiraterone Acetate as single agents (+5mg
prednison 2dd)
Period 2: 200mg Niraparib/1000mg Abiraterone Acetate as single agents
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1.Male 2. >/= 18 years or older 3. Signed ICF, documenting that purpose and procedures are understood and patient is willing to participate in study. 4. Histologically or cytologically confirmed adenocarcinoma of the prostate. 5.Diagnosed with mCRPC, who in the opinion of the investigator may benefit from treatment in this study. 6.Able to continue gonadotropin-releasing hormone analogues (GnRHa) therapy during the study if not surgically castrate (ie, participants who have not undergone bilateral orchiectomy). 7.Criterion modified per Amendment 1. 7.1 Participants who received prior therapy with enzalutamide or apalutamide must have at least an 8-week or a 6-week washout, respectively, before the first dose of study treatment. Participants who received prior therapy with other anti-androgens (eg, bicalutamide, flutamide, nilutamide) must have at least a 2-week washout before the first dose of the study treatment. 8.Eastern Cooperative Oncology Group Performance Status (ECOG PS) of =1.5x109/L b.Hemoglobin >=9.0 g/dL independent of transfusion within the last 4 weeks c.Platelet count >=100x109/L independent of transfusion within the last 4 weeks d.Serum albumin >=3.0 g/dL e.Serum creatinine =60 mL/min/1.73 m2 using the MDRD or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation f.Serum potassium >=3.5 mmol/L g.Serum total bilirubin
Exclusion criteria
Exclusion criteria: 1.Symptomatic brain metastases. 2. Criterion modified per Amendment 1. 2.1 Prior disease progression during treatment with AA alone or when combined with a PARP inhibitor (PARPi). Prior discontinuation of treatment with AA or PARPi due to AA- or PARPi-related toxicity. 3.History or current diagnosis of MDS/AML. 4.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.Malignancy that is considered cured with minimal risk of recurrence. 5.Known allergies, hypersensitivity, or intolerance to niraparib or AA or the corresponding excipients of niraparib/AA. 6. Any medical condition that would make prednisone use contraindicated. 7.Active hepatitis B virus (eg, hepatitis B surface antigen [HBsAg] reactive) or active hepatitis C virus (HCV) (eg, HCV ribonucleic acid [RNA] [qualitative] is detected). 8.Human immunodeficiency virus (HIV)-positive participants 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 15.c, a change is made to avoid a potential drug-drug interaction with the study drug) c.Receiving antiretroviral therapy that may interfere with study treatment (consult the sponsor for review of medication prior to enrollment) d. CD4 count
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: - PK parameters (Cmax,ss, AUC0-24h,ss, and test-to reference ratios for these parameters) of niraparib and Abiraterone Acetate at steady state. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: - PK parameters (Cmax, AUC0-168h and test-to reference ratios for these parameters) of niraparib and Abiraterone Acetate after a single dose. - PD parameter (serum testosterone levels and test to-reference ratio) at steady state. - Incidence and severity of AEs and clinical laboratory safety. | — |
Countries
Netherlands
Outcome results
None listed