An open-label, randomized study to assess the relative bioavailability (BA) and bioequivalence (BE) of fixed-dose combination (FDC) formulations of niraparib plus abiraterone acetate (AA) compared to niraparib and AA co-administered as single agents in men with prostate cancer
- Conditions
- prostate cancerprostate carcinoma10038597
- Registration Number
- NL-OMON52439
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
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.
9.Toxicity associated with prior chemotherapy or radiotherapy has resolved to
Grade <=1 (except alopecia, local skin fibrosis/reaction or Grade <=2 neuropathy)
at screening.
10.At screening, the following laboratory parameters must be met:
a.Absolute neutrophil count (ANC) >=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 <=1.5×upper limit of normal (ULN), or a calculated creatinine
clearance >=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 <=1.5×ULN (Note: In participants with Gilbert*s
syndrome, if total bilirubin is >1.5×ULN, measure direct and indirect
bilirubin, and if direct bilirubin is <=1.5×ULN, participant may be eligible)
h.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <=3xULN
11. Criterion modified per Amendment 1.
11.1 While on study medication and for 3 months following the last dose of
study medication, a male participant must agree to use an adequate
contraception method as deemed appropriate by the investigator and as specified
in Protocol Section 5.3. Lifestyle Considerations.
12. Ability to provide a blood sample for determination of HRR gene alteration
status.
13. Willing to provide a tumor sample (archival) for determination of HRR gene
alteration
status.
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 < 350 at screening
e.An acquired immunodeficiency syndrome-defining opportunistic infection within
6 months of the start of screening
9 .<=21 days prior to Study Day 1 received or had
a. chemotherapy or immunotherapy for treatment of prostate cancer
b. investigational agent for treatment of prostate cancer
10. Active or symptomatic viral hepatitis or chronic liver disease; ascites or
bleeding disorders secondary to hepatic dysfunction.
11. Moderate or Severe hepatic impairment Class B or C per Child-Pugh
classification system.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>- PK parameters (Cmax,ss, AUC0-24h,ss, and test-to reference ratios for these<br /><br>parameters) of niraparib and Abiraterone Acetate at steady state.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>- PK parameters (Cmax, AUC0-168h and test-to reference ratios for these<br /><br>parameters) of niraparib and Abiraterone Acetate after a single dose.<br /><br>- PD parameter (serum testosterone levels and test to-reference ratio) at<br /><br>steady state.<br /><br>- Incidence and severity of AEs and clinical laboratory safety.</p><br>