A Phase 3 Study of Niraparib in Combination with Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants with Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)
- Conditions
- Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)MedDRA 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
- EUCTR2020-002209-25-PL
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 696
1. 18 years of age or older
2. Criterion modified per Amendment 2.
2.1. Pathological diagnosis of prostate adenocarcinoma.
3. Criterion deleted per Amendment 1.
4. Criterion modified per Amendment 2.
4.1. Metastatic dsease documented by conventional imaging with CT or MRI (for soft tissue lesions) or 99mTc bone scan (for bone lesions). Participants with a single bone lesion on 99mTc bone scan with no other non-nodal metastatic disease must have confirmation of bone metastasis by CT or MRI.
a. Participants with lymph node-only disease are not eligible.
5. Criterion modified per Amendment 1.
5.1. Must have at least one of the deleterious germline or somatic HRR gene alterations listed in Table 4.
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) Grade =2.
7. Androgen deprivation therapy (either medical or surgical castration) must have been started =14 days prior to randomization and participants be willing to continue ADT through the treatment phase. Participants who start a GnRH agonist =28 days prior to randomization will be required to take a first-generation anti-androgen for =14 days prior to randomization. The anti-androgen must be discontinued prior to randomization.
8. Criterion modified per Amendment 1.
8.1. Criterion modified per Amendment 2.
8.2. Participants who have received prior docetaxel treatment must meet the following criteria:
a. Received a maximum of 6 cycles of docetaxel therapy for mCSPC b. Received the last dose of docetaxel =3 months prior to randomization
c. Maintained a response to docetaxel of stable disease or better, by investigator assessment of imaging and/or PSA, prior to randomization.
9. Criterion modified per Amendment 1.
9.1. Criterion modified per Amendment 2.
9.2. Other allowed prior therapy for mCSPC:
a. Maximum of 1 course of radiation and 1 surgical intervention for symptomatic control of prostate cancer (eg, uncontrolled pain, impending spinal cord compression or obstructive symptoms). Participants with radiation or surgical interventions to all known sites of metastatic disease will be excluded from trial participation. Radiation must be completed prior to randomization.
b. Up to a maximum of 6 months of ADT prior to randomization.
c. Up to a maximum of 45days of AAP prior to randomization.
d. Up to a maximum of 2 weeks of ketoconazole for prostate cancer prior to randomization.
10. Criterion modified per Amendment 2.
10.1. Allowed prior treatments for localized prostate cancer include radical prostatectomy (with or without lymph node dissection), radiation therapy, and other locally directed treatments to the prostate per institutional standards of care.
a. Participants who received ADT or first-generation anti-androgens for the treatment of localized prostate cancer
i. ADT: must have had =3 years total and must have completed =1 year prior to randomization
ii. First-generation anti-androgen: must have had =3 years total and must have completed =1 year prior to randomization.
11. Criterion modified per Amendment 1.
11.1. Clinical laboratory values at Screening:
a. Absolute neutrophil count =1.5 x 10^9/L
b. Hemoglobin =9.0 g/dL, independent of transfusions for at least 28 days
c. Platelet count =100 x 10^9/L
d. Creatinine = 2 x upper limit of normal (ULN)
e. Serum potassium =3.5 mmol/L
f. Serum total bilirubin =1.5× ULN or direct bilirubin =1 x ULN (Note: In participants with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin, and if d
1. Pathological finding consistent with small cell ductal or neuroendocrine carcinoma of the prostate.
2. Prior treatment with a PARP inhibitor.
3. Criterion modified per Amendment 1.
3.1. Criterion modified per Amendment 2.
3.2. Prior AR-targeted therapy (eg, apalutamide, enzalutamide,
darolutamide), immunotherapy, or radiopharmaceutical agents for prostate cancer with the Exception: allowed prior therapies are noted in inclusion criteria 9.2.
4. Criterion deleted per Amendment 2.
5. History of adrenal dysfunction
6. Long-term use of systemically administered corticosteroids (>5 mg of prednisone or the equivalent) during the study is not allowed. Short-term use (=4 weeks, including taper) and locally administered steroids (eg, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated.
7. 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. breast cancer – adequately treated lobular carcinoma in situ or ductal carcinoma in situ;
d. malignancy that is considered cured with minimal risk of recurrence.
8. History or current diagnosis of MDS/AML.
9. Current evidence within 6 months prior to randomization of any of the following: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, clinically significant arterial or venous thromboembolic events (ie, pulmonary embolism), or clinically significant ventricular arrhythmias.
10. Presence of sustained uncontrolled hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg). Participants with a history of hypertension are allowed, provided that blood pressure is controlled to within these limits by an antihypertensive
treatment.
11. Known allergies, hypersensitivity, or intolerance to the excipients of niraparib, AA, or niraparib/AA FDC (refer to the IBs for niraparib and AA).
12. Current evidence of any medical condition that would make prednisone use contraindicated.
13. Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the planned first dose of study medication.
14. Participants who have had the following =28 days prior to randomization:
a. A transfusion (platelets or red blood cells);
b. Hematopoietic growth factors;
c. Major surgery (sponsor should be consulted regarding what constitutes major surgery).
15. Criterion was deleted per Amendment 1
16. Human immunodeficiency virus positive participants with 1 or more of the following:
a. Not receiving highly active antiretroviral therapy or on antiretroviral therapy for less than 4 weeks.
b. Receiving antiretroviral therapy that may interfere with the study medication (consult the sponsor for review of medication prior to enrollment).
c. A change in antiretroviral therapy within 6 months of the start of screening (except if, after consultation with the sponsor on exclusion criterion 16.b, a change is made to avoid a potential drug-drug interaction with the study medication).
d. CD4 count <350 at screening.
e. An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening.
f. Human immunodeficiency virus load > 400 copies/mL.
17.Active or s
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method