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NCT Number: NCT04497844

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-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

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).

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This study is active but is not currently recruiting participants.

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Key information

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Asociacion de Beneficencia Hospital Sirio Libanes, Buenos Aires, Argentina

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About this study

Prostate cancer is a heterogenous disease and recent genomic analyses have highlighted specific germline and somatic mutations and alternative driver growth signaling pathways in patients with metastatic disease. Abiraterone acetate plus prednisone (AAP) is an established standard of care for the treatment of participants with mCSPC and is included in widely accepted clinical treatment guidelines. Niraparib in combination with AAP has been approved for the treatment of BRCA-mutated Metastatic Castration-Resistant Prostate Cancer (mCRPC). Niraparib is an investigational agent in the Metastatic Castration-Sensitive Prostate Cancer (mCSPC) population. Whether the addition of niraparib to the AAP standard of care may improve initial disease control and long-term outcomes compared with AAP alone in a biomarker selected mCSPC population is being evaluated on this trial. The study will consist of 4 phases; a Prescreening Phase for biomarker evaluation for eligibility only, a Screening Phase, a Treatment Phase, and a Follow-up Phase. Efficacy evaluations include the following: tumor measurements by computed tomography (CT), magnetic resonance imaging (MRI; abdomen, chest, and pelvis), Technetium-99m (99mTc) bone scans, serum prostate sensitive antigen (PSA) evaluations, and patient reported outcomes (PROs). Safety evaluations include incidence of adverse events and clinical laboratory parameters.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Niraparib

Drug

Participants will receive Niraparib 200 mg once daily.

Abiraterone Acetate (AA)

Drug

Participants will receive AA 1000 mg once daily.

Prednisone

Drug

Participants will receive prednisone 5 mg once daily.

Placebo for Niraparib

Drug

Participants will receive matching placebo for Niraparib once daily.

Primary outcomes

  1. Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator

    Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months

    rPFS: time interval from date of randomization to first date of radiographic progression as assessed by investigator or death due to any cause, whichever occurred first. rPFS was determined by: (1) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) per response evaluation criteria in solid tumors (RECIST) 1.1; (2) progression of bone lesions observed by bone scan per prostate cancer working group 3 (PCWG3) criteria: bone progression was confirmed by subsequent scan greater than or equal to (>=) 6 weeks later. Week 8 scan was baseline to which all subsequent scans were compared to determine progression. A confirmatory scan with >=2 new lesions indicated progression; A confirmatory scan not showing >=2 new lesions means no progression. If Week 8 scan shows <2 new bone lesions compared to baseline, first scan with >=2 new lesions compared to Week 8 scan indicated progression, when confirmed by a subsequent scan >=6 weeks later.

  2. HRR Effector Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator

    Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months

    rPFS: time interval from date of randomization to first date of radiographic progression as assessed by investigator or death due to any cause, whichever occurred first. rPFS was determined by: (1) progression of soft tissue lesions measured by CT or MRI per RECIST 1.1; (2) progression of bone lesions observed by bone scan per PCWG3 criteria: bone progression was confirmed by subsequent scan >= 6 weeks later. Week 8 scan was baseline to which all subsequent scans were compared to determine progression. A confirmatory scan with >=2 new lesions indicated progression; A confirmatory scan not showing >=2 new lesions means no progression. If Week 8 scan shows <2 new bone lesions compared to baseline, first scan with >=2 new lesions compared to Week 8 scan indicated progression, when confirmed by a subsequent scan >=6 weeks later.

  3. All HRR: Radiographic Progression-free Survival (rPFS) Assessed by Investigator

    Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months

    rPFS: time interval from date of randomization to first date of radiographic progression as assessed by investigator or death due to any cause, whichever occurred first. rPFS was determined by: (1) progression of soft tissue lesions measured by CT or MRI per RECIST 1.1; (2) progression of bone lesions observed by bone scan per PCWG3 criteria: bone progression was confirmed by subsequent scan >= 6 weeks later. Week 8 scan was baseline to which all subsequent scans were compared to determine progression. A confirmatory scan with >=2 new lesions indicated progression; A confirmatory scan not showing >=2 new lesions means no progression. If Week 8 scan shows <2 new bone lesions compared to baseline, first scan with >=2 new lesions compared to Week 8 scan indicated progression, when confirmed by a subsequent scan >=6 weeks later.

Secondary outcomes

  1. BRCA Subgroup: Time to Symptomatic Progression

    Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months

    Time to symptomatic progression was defined as time from the date of randomization to the date of any of the following (whichever occurred first): (a) the use of external beam radiation therapy for skeletal or pelvic symptoms, (b) the need for tumor-related orthopedic surgical intervention, (c) other cancer-related procedures (example: nephrostomy insertion, bladder catheter insertion, external beam radiation therapy, or surgery for tumor symptoms), (d) cancer-related morbid events (that is, fracture [symptomatic and/or pathologic], cord compression, urinary obstructive events), (e) initiation of a new systemic anti-cancer therapy because of cancer symptoms.

  2. HRR Effector Subgroup: Time to Symptomatic Progression

    Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months

    Time to symptomatic progression was defined as time from the date of randomization to the date of any of the following (whichever occurred first): (a) the use of external beam radiation therapy for skeletal or pelvic symptoms, (b) the need for tumor-related orthopedic surgical intervention, (c) other cancer-related procedures (example: nephrostomy insertion, bladder catheter insertion, external beam radiation therapy, or surgery for tumor symptoms), (d) cancer-related morbid events (that is, fracture [symptomatic and/or pathologic], cord compression, urinary obstructive events), (e) initiation of a new systemic anti-cancer therapy because of cancer symptoms.

  3. All HRR: Time to Symptomatic Progression

    Time frame: From date of randomization (Day -3 to Day 1) up to approximately 49 months

    Time to symptomatic progression was defined as time from the date of randomization to the date of any of the following (whichever occurred first): (a) the use of external beam radiation therapy for skeletal or pelvic symptoms, (b) the need for tumor-related orthopedic surgical intervention, (c) other cancer-related procedures (example: nephrostomy insertion, bladder catheter insertion, external beam radiation therapy, or surgery for tumor symptoms), (d) cancer-related morbid events (that is, fracture [symptomatic and/or pathologic], cord compression, urinary obstructive events), (e) initiation of a new systemic anti-cancer therapy because of cancer symptoms.

  4. Overall Survival (OS)

    Time frame: From date of randomization (Day -3 to Day 1) up to 83 months

  5. Time to Subsequent Therapy

    Time frame: From date of randomization (Day -3 to Day 1) up to 83 months

  6. Number of Participants With Treatment-emergent Serious Adverse Events

    Time frame: From Cycle 1 Day 1 up to 83 months

  7. Number of Participants With Treatment-emergent Adverse Events by Severity

    Time frame: From Cycle 1 Day 1 up to 83 months

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study title

A Phase 3 Randomized, Placebo-controlled, Double-blind 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-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

Acronym: AMPLITUDE

Important dates

Study start
2020
Primary completion
2025
Study completion
2027
First posted
Aug 4, 2020
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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