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) (AMPLITUDE)

• ClinicalTrials.gov Identifier: NCT04497844
• Recruitment Status: Recruiting
• First Posted: August 4, 2020
• Last Update Posted: May 25, 2022
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: July 31, 2020
• First Posted Date: August 4, 2020
• Last Update Posted Date: May 25, 2022
• Actual Study Start Date: September 23, 2020
• Estimated Primary Completion Date: November 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 31, 2020)

Radiographic Progression-free Survival (rPFS) [ Time Frame: Up to 47 months ]

rPFS is defined as time from randomization date to date of radiographic progression or death, whichever occurs first. Radiographic progression will be evaluated by Prostate Cancer Working Group 3 (PCWG3) criteria.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 31, 2020)

• Overall Survival (OS) [ Time Frame: Up to 78 months ]
  OS is defined as the time from date of randomization to date of death from any cause.
• Symptomatic Progression-free Survival [ Time Frame: Up to 47 months ]
  Symptomatic progression free survival is defined as time from the date of randomization to the onset of symptoms consistent with progression of metastatic prostate cancer.
• Time to Subsequent Therapy [ Time Frame: Up to 47 months ]
  Time to Subsequent Therapy is defined as the time from date of randomization to the date of initiation of subsequent therapy for prostate cancer.
• Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 78 months ]
  An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. AE does not necessarily have a causal relationship with intervention.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official 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)
• Brief Summary: 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).
• Detailed Description: 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 (AA-P) is an established standard of care for the treatment of participants with mCSPC and is included in widely accepted clinical treatment guidelines. Niraparib is an investigational agent in the castration-sensitive cancer population and has been approved for the treatment of ovarian cancer. The addition of niraparib to the AA-P backbone regimen may improve initial disease control and long-term outcomes compared with AA-P alone in a biomarker selected population. 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Metastatic Castrate Sensitive Prostate Cancer

Intervention

• Drug: Niraparib
  Participants will receive Niraparib 200 mg once daily.
• Drug: Abiraterone acetate (AA)
  Participants will receive AA 1000 mg once daily.
• Drug: Prednisone
  Participants will receive prednisone 5 mg once daily.
• Drug: Placebo for Niraparib
  Participants will receive matching placebo for Niraparib once daily.

Study Arms

• Experimental: Niraparib with Abiraterone Acetate plus Prednisone (AA-P)
  Participants will receive the following in each 28-day treatment cycle: niraparib 200 milligrams (mg), abiraterone acetate (AA) 1000 mg plus prednisone 5 mg once daily.
  Interventions:

  • Drug: Niraparib
  • Drug: Abiraterone acetate (AA)
  • Drug: Prednisone
• Experimental: AA plus Prednisone (AA-P)
  Participants will receive the following in each 28-day treatment cycle: matching placebo for Niraparib along with AA 1000 mg plus prednisone 5 mg once daily.
  Interventions:

  • Drug: Prednisone
  • Drug: Placebo for Niraparib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 31, 2020): 788
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 7, 2027
• Estimated Primary Completion Date: November 15, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Argentina, Australia, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Netherlands, New Zealand, Poland, Portugal, Russian Federation, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Moldova, Republic of

Administrative Information

• NCT Number: NCT04497844
• Other Study ID Numbers: CR108852; 2020-002209-25 ( EudraCT Number ); 67652000PCR3002 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: May 2022