A Phase 3 Study of Niraparib in Combination with Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Patients with Metastatic Prostate Cancer
- Conditions
- Metastatic Prostate CancerMedDRA version: 21.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-003364-12-PL
- Lead Sponsor
- Janssen-Cilag International N.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 1100
1. Criterion modified per Amendment 3
1.1 Criterion modified per Amendment 4
1.2 Criterion modified per Amendment 5
1.3 HRR gene alteration status (as identified by the sponsor's required assays or local testing for HRR gene alteration) as follows:
a. Cohort 1: positive for HRR gene alteration
b. Cohort 2: not positive for HRR gene alteration (ie, no HRR gene alteration)
c. Cohort 3 : positive for HRR gene alteration, see Attachment 4
2. Metastatic disease documented by radiographic imaging
3. Metastatic prostate cancer in the setting of castrate levels of
testosterone =50 ng/dL on a GnRHa or bilateral orchiectomy as
evidenced by prostate-specific antigen (PSA) progression or
radiographic progression
4. Able to continue GnRHa during the study if not surgically castrate
5. ECOG PS Grade of 0 or 1
6 Score of =3 on the Brief Pain Inventory-Short Form (BPI-SF) Question #3 (worst pain in last 24 hours).
7. Clinical laboratory values at Screening:
a. Absolute neutrophil count (ANC) =1.5 x 10^9/L.
b. Hemoglobin =9.0 g/dL, independent of transfusions for at least 30
days.
c. Platelet count =100 x 10^9/L.
d. Serum albumin =3.0 g/dL.
e. Creatinine clearance =30 mL/min either calculated or directly
measured via 24-hour urine collection.
f. Serum potassium =3.5 mmol/L.
g. 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).
h. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3 x ULN.
8. Able to swallow the study drug tablets and capsules whole.
9. Criterion modified per Amendment 5
9.1 While on study drug and for 3 months following the last dose of study drug ,a male subject must agree to use an adequate contraception method as deemed appropriate by the investigator (specified in Section 4.4 Lifestyle Considerations) and agree not to donate sperm.
10. Willing and able to adhere to the prohibitions and restrictions specified in the protocol.
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 260
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 840
1. Prior treatment with a PARP inhibitor
2. Systemic therapy (ie, novel second-generation AR-targeted therapy
such as enzalutamide, apalutamide, or darolutamide; taxane-based
chemotherapy, or more than 4 months of AAP prior to randomization) in the mCRPC setting; or AAP outside of the mCRPC setting.
3. For subjects who received 2 to 4 months of AAP prior to
randomization for the treatment of mCRPC, evidence of progression by PSA (per PCWG3) during screening. These potential subjects are
required to have 2 PSA values during the Prescreening and Screening
Phases. The second PSA value should be within 2 weeks of
randomization. If PSA rise is thought to be due to flare, the investigator should confirm that there is no radiographic progression.
4. Symptomatic brain metastases
5. History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
6. Other prior malignancy =2 years prior to randomization, or malignancy that currently requires active systemic therapy
7. Severe or unstable angina, myocardial infarction or ischemia requiring coronary artery bypass graft or stent within the previous 6 months, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g. adequate cardiac function), or clinically significant ventricular arrhythmias within 6 months prior to randomization or New York Heart Association (NYHA) Class II to IV heart disease
8. Presence of uncontrolled hypertension
9. Current evidence of any of the following:
a. Any medical condition that would make prednisone use contraindicated
b. Any chronic medical condition requiring a higher equivalent dose of corticosteroid than 10 mg prednisone (or equivalent) per day
10. Criterion modified per Amendment 5
10.1 Active or symptomatic viral hepatitis or chronic liver disease (as evidenced by ascites, encephalopathy or bleeding disorders secondary to hepatic dysfunction).
11. History of adrenal dysfunction
13. Subjects who are receiving opioid analgesics at the time of screening
14. Active human immunodeficiency virus (HIV) infection
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effectiveness of niraparib plus AAP compared to AAP plus placebo.;Secondary Objective: * To assess the clinical benefit of niraparib plus AAP compared to AAP plus placebo<br>* To characterize the safety profile of niraparib when given with AAP compared to AAP with placebo;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 at<br>Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, and then every 12 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): * OS<br>* Time-to-symptomatic progression<br>* Time-to-initiation of cytotoxic chemotherapy<br>* Observed plasma concentrations of niraparib and abiraterone and<br>estimated population PK and exposure parameters for niraparib<br>* Incidence and severity of AEs<br>* Clinical laboratory test results;Timepoint(s) of evaluation of this end point: Assessments of the secondary endpoints are variable but carried out on a regular basis from C1D1 through the follow up as described in the endpoint requirements