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-DE
- 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 positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI).
3. Criterion modified per Amendment 2
3.1 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. Criterion modified per Amendment 2
7.1 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. Criterion modified per Amendment 2
2.1 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. Criterion modified per Amendment 2
3.1 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. Subjects with a history of hypertension are allowed, if BP is controlled to within these limits by anti-hypertensive treatment.
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) once daily.
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
12. Known allergies, hypersensitivity, or intolerance to AA or niraparib or the corresponding excipients
13. Subjects who are receiving opioid analgesics at the time of screening
14. Human immunodeficiency virus (HIV) positive subjects with 1 or more of the following:
a. Not receiving highly active antiretroviral therapy.
b. Receiving antiretroviral therapy that may interfere with the study drug
c. A change in antiretroviral therapy within 6 months of the start of screening
d. CD4 count <350 at screening.
e. An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening.
15. Subjects who have had the following =28 days prior to randomization:
a. A transfusion (platelets or red blood cells).
b. Hematopoietic growth factors.
c. An investigational agent for prostate cancer.
d. Major surgery (sponsor should be consulted regarding what constitutes major surgery).
e. Radiation therapy
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 and AAP compared to AAP and placebo.;Secondary Objective: *To assess the clinical benefit of niraparib and AAP compared to AAP and placebo<br>*To characterize the pharmacokinetics (PK) of niraparib when given with AAP and abiraterone trough levels<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 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 estimated population PK and exposure parameters for niraparib<br>* Incidence and severity of AEs<br>* Clinical laboratory test results<br><br>;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