A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination with Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Subjects with Metastatic Prostate Cancer

Overview

About this study

The purpose of this study is to evaluate the effectiveness of niraparib in combination with abiraterone acetate and prednisone (AA-P) compared to AA-P plus placebo.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Signed informed consent form (ICF).
  • ≥ 18 years of age (or the local legal age of consent)
  • Histologically confirmed prostate cancer.
  • Can provide a blood sample for determination of HRR gene alterations.
  • Willing to provide a tumor tissue sample (archival or recently collected) for determination of HRR gene alterations.
  • Metastatic prostate cancer in the setting of castrate levels of testosterone (i.e., taking a gonadotropin releasing hormone analog [GnRHa], or history of bilateral orchiectomy at study entry).
  • HRR gene alteration status (as identified by the sponsor’s required assays or local testing for HRR gene alteration as follows:
    • Cohort 1: positive for HRR gene alteration;
    • Cohort 2: not positive for HRR gene alteration (ie, no HRR gene alteration);
    • Cohort 3: see Attachment 4.
  • Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI).
  • 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.
  • Able to continue GnRHa during the study if not surgically castrate.
  • Eastern Cooperative Oncology Group Performance Score (ECOG PS) Grade of 0 or 1.
  • Score of ≤ 3 on the Brief Pain Inventory-Short Form (BPI-SF) Question #3 (worst pain in last 24 hours).
  • Clinical laboratory values at Screening:
    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9 /L;
    • Hemoglobin ≥ 9.0 g/dL, independent of transfusions for at least 30 days;
    • Platelet count ≥ 100 x 10^9/L;
    • Serum albumin ≥ 3.0 g/dL;
    • Creatinine clearance ≥ 30 mL/min either calculated or directly measured via 24-hour urine collection;
    • Serum potassium ≥ 3.5 mmol/L; 
    • 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);
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
  • Able to swallow the study drug tablets and capsules whole.
  • To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must agree while on study drug and for 3 months following the last dose of study drug to:
    • Use a condom during sexual activity;
    • Not donate sperm.
  • Willing and able to adhere to the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

  • Prior treatment with a PARP inhibitor.
  • Systemic therapy (i.e., novel second-generation AR-targeted therapy such as enzalutamide, apalutamide, or darolutamide; taxane-based chemotherapy, or more than 4 months of AA-P prior to randomization) in the mCRPC setting; or AA-P outside of the mCRPC setting.
  • For subjects who received 2 to 4 months of AA-P 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.
  • Symptomatic brain metastases.
  • History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).
  • Other prior malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) ≤ 2 years prior to randomization, or malignancy that currently requires active systemic therapy. 
  • 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., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization or New York Heart Association (NYHA) Class II to IV heart disease.
  • Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] ≥ 160 mmHg or diastolic BP ≥ 100 mmHg). Subjects with a history of hypertension are allowed, if BP is controlled to within these limits by anti-hypertensive treatment.
  • Current evidence of any of the following:
    • Any medical condition that would make prednisone use contraindicated;
    • Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone (or equivalent) once daily.
  • Active or symptomatic viral hepatitis or chronic liver disease (as evidenced by ascites or bleeding disorders secondary to hepatic dysfunction).
  • History of adrenal dysfunction 
  • Known allergies, hypersensitivity, or intolerance to AA or niraparib or the corresponding excipients (refer to Investigator's Brochures).
  • Subjects who are receiving opioid analgesics at the time of screening.
  • Human immunodeficiency virus (HIV) positive subjects with 1 or more of the following:
    • Not receiving highly active antiretroviral therapy;
    • Receiving antiretroviral therapy that may interfere with the study drug (consult the sponsor for review of medication prior to enrollment);
    • A change in antiretroviral therapy within 6 months of the start of screening (except if, after consultation with the sponsor on exclusion criterion 14.b, a change is made to avoid a potential drug-drug interaction with the study drug);
    • CD4 count < 350 at screening;
    • An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening.
  • Subjects who have had the following ≤ 28 days prior to randomization:
    • A transfusion (platelets or red blood cells);
    • Hematopoietic growth factors;
    • An investigational agent for prostate cancer;
    • Major surgery (sponsor should be consulted regarding what constitutes major surgery);
    • Radiation therapy.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Alan Bryce, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

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Jacksonville, Fla.

Mayo Clinic principal investigator

Winston Tan, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

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More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20484365

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