Metastatic Castration-sensitive Prostate Cancer
Conditions
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 (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.
Interventions
DRUGNiraparib
Participants will receive Niraparib 200 mg once daily.
Participants will receive AA 1000 mg once daily.
DRUGPrednisone
Participants will receive prednisone 5 mg once daily.
Participants will receive matching placebo for Niraparib once daily.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator | 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. |
| HRR Effector Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator | 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. |
| All HRR: Radiographic Progression-free Survival (rPFS) Assessed by Investigator | 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
| Measure | Time frame | Description |
|---|---|---|
| BRCA Subgroup: Time to Symptomatic Progression | 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. |
| HRR Effector Subgroup: Time to Symptomatic Progression | 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. |
| All HRR: Time to Symptomatic Progression | 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. |
| Overall Survival (OS) | From date of randomization (Day -3 to Day 1) up to 83 months | — |
| Time to Subsequent Therapy | From date of randomization (Day -3 to Day 1) up to 83 months | — |
| Number of Participants With Treatment-emergent Serious Adverse Events | From Cycle 1 Day 1 up to 83 months | — |
| Number of Participants With Treatment-emergent Adverse Events by Severity | From Cycle 1 Day 1 up to 83 months | — |
Countries
Argentina, Australia, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Malaysia, Mexico, Netherlands, New Zealand, Poland, Portugal, Puerto Rico, Russia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Pre-assignment details
The results presented are based on the primary completion date (07 January 2025). Remaining results will be reported within a year of study completion.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical 85 years and over | 6 Participants |
| Age, Categorical Adults (18-64 years) | 135 Participants |
| Age, Categorical From 65 to 84 years | 212 Participants |
| Age, Continuous | 67.3 years STANDARD_DEVIATION 8.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 292 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 21 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants |
| Race (NIH/OMB) Asian | 77 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 257 Participants |
| Region of Enrollment ARGENTINA | 15 Participants |
| Region of Enrollment AUSTRALIA | 9 Participants |
| Region of Enrollment BELARUS | 7 Participants |
| Region of Enrollment BELGIUM | 9 Participants |
| Region of Enrollment BRAZIL | 30 Participants |
| Region of Enrollment BULGARIA | 3 Participants |
| Region of Enrollment CANADA | 14 Participants |
| Region of Enrollment CHINA | 53 Participants |
| Region of Enrollment CZECH REPUBLIC | 3 Participants |
| Region of Enrollment DENMARK | 10 Participants |
| Region of Enrollment FRANCE | 15 Participants |
| Region of Enrollment GERMANY | 6 Participants |
| Region of Enrollment HUNGARY | 7 Participants |
| Region of Enrollment ISRAEL | 11 Participants |
| Region of Enrollment ITALY | 56 Participants |
| Region of Enrollment MALAYSIA | 4 Participants |
| Region of Enrollment MEXICO | 3 Participants |
| Region of Enrollment NETHERLANDS | 1 Participants |
| Region of Enrollment NEW ZEALAND | 9 Participants |
| Region of Enrollment POLAND | 12 Participants |
| Region of Enrollment PORTUGAL | 2 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 9 Participants |
| Region of Enrollment SOUTH AFRICA | 3 Participants |
| Region of Enrollment SOUTH KOREA | 19 Participants |
| Region of Enrollment SPAIN | 21 Participants |
| Region of Enrollment SWEDEN | 2 Participants |
| Region of Enrollment TAIWAN | 11 Participants |
| Region of Enrollment THAILAND | 3 Participants |
| Region of Enrollment TURKEY | 45 Participants |
| Region of Enrollment UKRAINE | 14 Participants |
| Region of Enrollment UNITED KINGDOM | 11 Participants |
| Region of Enrollment UNITED STATES | 30 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 348 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 108 / 348 | 85 / 348 |
| other Total, other adverse events | 326 / 348 | 338 / 347 |
| serious Total, serious adverse events | 96 / 348 | 136 / 347 |
Outcome results
None listed