A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-MutatedProstatic Neoplasms (mCSPC) (AMPLITUDE)

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 3

Conditions: Prostatic Neoplasms

Treatments: Drug: Placebo FDC; Drug: Prednisone; Combination Product: Niraparib+ Abiraterone acetate fixed dose combination (FDC); Drug: Placebo AA; Drug: Abiraterone acetate (AA)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04497844

CR108852

2023-506365-64-00 (Registry Identifier)

2023

67652000PCR3002 (Other Identifier)

2020-002209-25 (EudraCT Number)

Details and patient eligibility

About

The purpose of the study is to determine if the combination of niraparib with Abiraterone Acetate (AA) plus prednisone compared with AA plus prednisone in participants with deleterious germline or somatic Homologous Recombination Repair (HRR) gene-mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) provides superior efficacy in improving radiographic progression-free survival (rPFS).

Enrollment: 696 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Pathological diagnosis of prostate adenocarcinoma
• Must have appropriate deleterious homologous recombination repair (HRR) gene alteration
• Metastatic disease as documented by conventional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) (for soft tissue lesions) or 99mTc bone scan (for bone lesions). Participants with a single bone lesion on Technetium-99m (99mTc) bone scan with no other non-nodal metastatic disease must have confirmation of bone metastasis by CT or MRI. Participants with lymph node-only disease are not eligible
• Androgen deprivation therapy (either medical or surgical castration) must have been started >=14 days prior to randomization and participants be willing to continue androgen deprivation therapy (ADT) through the treatment phase
• Other allowed prior therapy for metastatic castration-sensitive prostate cancer (mCSPC): (a) maximum of 1 course of radiation and 1 surgical intervention for symptomatic control of prostate cancer (example, 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 45 days of abiraterone acetate + prednisone (AA-P) prior to randomization (d) Up to a maximum of 2 weeks of ketoconazole for prostate cancer prior to randomization

Exclusion criteria

• Prior treatment with a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARP inhibitor)
• History of adrenal dysfunction
• Long-term use of systemically administered corticosteroids (greater than [>] 5 milligrams [mg] of prednisone or the equivalent) during the study is not allowed. Short-term use (<=4 weeks, including taper) and locally administered steroids (for example, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated
• History or current diagnosis of myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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696 participants in 2 patient groups

Niraparib with Abiraterone Acetate plus Prednisone (AAP)

Experimental group

Description:

Participants will receive the following in each 28-day treatment cycle: niraparib 200 milligrams (mg) + abiraterone acetate (AA) 1000 mg fixed dose combination (FDC) along with placebo for AA and prednisone 5 mg once daily.

Treatment:

Drug: Placebo AA

Combination Product: Niraparib+ Abiraterone acetate fixed dose combination (FDC)

Drug: Prednisone

Placebo for Niraparib + AA FDC plus AA and prednisone (AAP)

Active Comparator group

Description:

Participants will receive the following in each 28-day treatment cycle: matching placebo for Niraparib+AA FDC along with AA 1000 mg and prednisone 5 mg once daily.

Treatment:

Drug: Abiraterone acetate (AA)

Drug: Prednisone

Drug: Placebo FDC