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).
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)
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 (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.
Completion Date
Completion Date Type
Estimated
Conditions
Metastatic Castration-sensitive Prostate Cancer
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)
* 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)
Inclusion 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
* 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
Gender
Male
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04497844
Org Class
Industry
Org Full Name
Janssen Research & Development, LLC
Org Study Id
CR108852
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome Description
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 and Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Outcome Measure
Radiographic Progression-free Survival (rPFS)
Outcome Time Frame
Up to 47 months
Secondary Ids
Secondary Id
67652000PCR3002
Secondary Id
2020-002209-25
Secondary Id
2023-506365-64-00
Secondary Outcomes
Outcome Description
OS is defined as the time from date of randomization to date of death from any cause.
Outcome Time Frame
Up to 78 months
Outcome Measure
Overall Survival (OS)
Outcome Description
Time to symptomatic progression is defined as time from the date of randomization to the date of any of the following (whichever occurs 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; d) cancer-related morbid events; e) initiation of a new systemic anti-cancer therapy because of cancer symptoms.
Outcome Time Frame
Up to 47 months
Outcome Measure
Time to Symptomatic Progression
Outcome Description
Time to Subsequent Therapy is defined as the time from date of randomization to the date of initiation of subsequent therapy for prostate cancer.
Outcome Time Frame
Up to 47 months
Outcome Measure
Time to Subsequent Therapy
Outcome Description
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.
Outcome Time Frame
Up to 78 months
Outcome Measure
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
MeSH Terms
NIRAPARIB
ABIRATERONE ACETATE
PREDNISONE
COUNTERFEIT DRUGS
ANDROSTENES
ANDROSTANES
STEROIDS
FUSED-RING COMPOUNDS
POLYCYCLIC COMPOUNDS
PREGNADIENEDIOLS
PREGNADIENES
PREGNANES
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS