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Trial record 1 of 1 for:    NCT03748641
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A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer (MAGNITUDE)

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ClinicalTrials.gov Identifier: NCT03748641
Recruitment Status : Recruiting
First Posted : November 21, 2018
Last Update Posted : October 9, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE November 19, 2018
First Posted Date  ICMJE November 21, 2018
Last Update Posted Date October 9, 2020
Actual Study Start Date  ICMJE January 25, 2019
Estimated Primary Completion Date July 21, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 17, 2020)
Cohort 1 and 3: Radiographic Progression Free Survival (rPFS) [ Time Frame: Up to 28 months ]
As per blinded independent central review, 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) as follows: progression of soft tissue lesions measured by computed tomography/magnetic resonance imaging as per response evaluation criteria in solid tumors (RECIST) 1.1; progression by bone lesions observed by bone scan and based on PCWG3. As per criteria, any bone progression must be confirmed by a subsequent scan greater than or equal to (>=) 6 weeks later. Week 8 scan will be baseline to which all subsequent scans will be compared to determine progression. Participants whose confirmatory scan shows >=2 new lesions will be considered to have bone scan progression and participants whose confirmatory scans did not show >= 2 new lesions will not be considered to have bone scan progression when compared to Week 8 scan.
Original Primary Outcome Measures  ICMJE
 (submitted: November 19, 2018)
Radiographic Progression Free Survival (rPFS) [ Time Frame: Approximately 40 months ]
rPFS is defined as time from date of randomization to date of radiographic progression or death, whichever occurs first. Radiographic progression will be evaluated by Prostate Cancer Working Group 3 (PCWG3) as follows: progression of soft tissue lesions measured by computed tomography/magnetic resonance imaging as per response evaluation criteria in solid tumors (RECIST) 1.1; progression by bone lesions observed by bone scan and based on PCWG3. As per criteria, any bone progression must be confirmed by a subsequent scan greater than or equal to (>=) 6 weeks later. Week 8 scan will be baseline to which all subsequent scans will be compared to determine progression. Bone progression is defined as one of the following: participants whose confirmatory scan shows >=2 new lesions will be considered to have bone scan progression and who did not show >= 2 new lesions will not be considered to have bone scan progression when compared to Week 8 scan.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2020)
  • Cohort 1: Overall survival (OS) [ Time Frame: Up to 66 months ]
    OS is defined as the time from date of randomization to date of death from any cause.
  • Cohort 1: Time to Symptomatic Progression [ Time Frame: Up to 28 months ]
    Time to symptomatic progression is defined as the need to initiate/record any of the following; a. the use of external beam radiation therapy (EBRT) for skeletal symptoms; b. the need for tumor-related orthopedic surgical intervention; c. other cancer-related procedures (for example: nephrostomy insertion, bladder catheter insertion, EBRT, or surgery for tumor symptoms other than skeletal); d. cancer-related morbid events (for example: fracture [symptomatic and/or pathologic, cord compression, urinary obstructive events); e. initiation of new systemic anti-cancer therapy because of cancer pain.
  • Cohort 1: Time to Initiation of Cytotoxic Chemotherapy [ Time Frame: Up to 28 months ]
    Time to initiation of cytotoxic chemotherapy is defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.
  • Cohort 1: Observed Plasma Concentrations of Niraparib [ Time Frame: Cycle 2 to 7; Each Cycle is of 28 days (Up to 7 months) ]
    Observed plasma concentrations of niraparib with descriptive statistics will be reported.
  • Cohort 1: Observed Trough Plasma Concentrations of Abiraterone [ Time Frame: Cycles 2 and 3; Each Cycle is of 28 days (Up to 3 months) ]
    Observed trough plasma concentrations of abiraterone with descriptive statistics will be reported.
  • Cohort 1: Number of Participants with Treatment-Emergent Adverse events (TEAEs) [ Time Frame: Up to 66 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. AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal product. TEAEs are those events that occur or worsen on or after first dose of study drug through 30 days after last dose of study drug.
  • Cohort 1: Number of Participants with Treatment-Emergent Adverse events by Severity [ Time Frame: Up to 66 months ]
    Adverse event is any untoward medical occurrence in clinical study participant administered a medicinal (investigational or non-investigational) product. AE does not necessarily have causal relationship with intervention. AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal product. TEAEs are those events that occur or worsen on or after first dose of study drug through 30 days after last dose of study drug. Severity criteria includes grades: 1) Mild: easily tolerated, causing minimal discomfort and no interference with everyday activities; 2) Moderate: sufficient discomfort to cause interference with normal activity; 3) Severe: extreme distress, significant impairment of functioning/incapacitation. Prevents everyday activities; 4) Life-threatening: urgent intervention indicated and 5) Death.
  • Cohort 1: Number of Participants with Laboratory Abnormalities as Measure of Safety [ Time Frame: Up to 66 months ]
    Number of participants with laboratory abnormalities (hematology, serum chemistry and liver function test) will be determined.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2018)
  • Overall survival (OS) [ Time Frame: Approximately up to 73 months ]
    OS is defined as the time from date of randomization to date of death from any cause.
  • Time to Chronic Opioid Use [ Time Frame: Approximately up to 73 months ]
    Time to chronic opioid use (oral opioid use for >=3 weeks; parenteral opioid use for >=7 days) is defined as the time from date of randomization to the first date of chronic opioid use.
  • Time to Pain Progression [ Time Frame: Approximately up to 73 months ]
    Time to pain progression is defined as the time from date of randomization to the date of the first observation of pain progression. Pain progression is defined as an increase by at least 2 points from baseline in the brief pain inventory-short form (BPI-SF) worst pain intensity (item 3) observed at 2 consecutive evaluations >= 3 weeks apart, or Initiation of short or long-acting opioids for pain.
  • Time to Initiation of Cytotoxic Chemotherapy [ Time Frame: Approximately up to 73 months ]
    Time to initiation of cytotoxic chemotherapy is defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.
  • Observed Plasma Concentrations of Niraparib [ Time Frame: Cycle 2: Day 1 (Predose, between 1 to 3 and 3 to 6 hours postdose); Cycle 3: Day 1 (Predose); Cycles 4 to 7: Day 1 (Predose or at least 3 hours postdose); each Cycle of 28 days ]
    Observed plasma concentrations of niraparib with descriptive statistics will be reported.
  • Observed Trough Plasma Concentrations of Abiraterone [ Time Frame: Cycles 2 and 3 (Each Cycle of 28 days): Day 1 (Predose) ]
    Observed trough plasma concentrations of abiraterone with descriptive statistics will be reported.
  • Number of Participants with Treatment-Emergent Adverse events (TEAEs) [ Time Frame: Approximately up to 73 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. AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal product. TEAEs are those events that occur or worsen on or after first dose of study drug through 30 days after last dose of study drug.
  • Number of Participants with Treatment-Emergent Adverse events by Severity [ Time Frame: Approximately up to 73 months ]
    An adverse event 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. AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal product. TEAEs are those events that occur or worsen on or after first dose of study drug through 30 days after last dose of study drug. Severity criteria includes grades:1) Mild: easily tolerated, causing minimal discomfort and no interference with everyday activities 2) Moderate: sufficient discomfort to cause interference with normal activity 3) Severe: extreme distress, significant impairment of functioning/incapacitation. Prevents everyday activities 4) Life-threatening: urgent intervention indicated 5) Death
  • Number of Participants with Laboratory Abnormalities as Measure of Safety [ Time Frame: Approximately up to 73 months ]
    Number of participants with laboratory abnormalities (hematology, serum chemistry and liver function test) will be determined.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer
Official Title  ICMJE A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects With Metastatic Prostate Cancer
Brief Summary The purpose of this study is to evaluate the effectiveness of niraparib in combination with abiraterone acetate plus prednisone (AAP) compared to AAP plus placebo.
Detailed Description This study will assess efficacy and safety of niraparib in combination with AAP for the treatment of participants with metastatic castration resistant prostate cancer. Niraparib is an orally available, highly selective poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, with potent activity against PARP-1 and PARP-2 deoxyribonucleic acid (DNA)-repair polymerases. AA is a pro-drug of abiraterone and selectively inhibits the enzyme 17 alpha-hydroxylase/C17,20-lyase (CYP17), which is found in the testes and adrenals, as well as in prostate tissues and tumors. In participants with metastatic prostate cancer, DNA-repair anomalies are identified in approximately 15 percent (%) to 20% of tumors. The study will consist of 4 phases: a prescreening phase for biomarker evaluation only, a screening phase, a treatment phase, and a follow up phase. During the prescreening phase participants will be evaluated for homologous recombination repair (HRR) gene alteration status and then will be assigned to one of the 2 cohorts based on their biomarker status. Treatment will be administered daily and is planned to be continuous until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. Efficacy, pharmacokinetics, biomarkers, participants reported outcomes and safety will be assessed. The total duration of study will be approximately 66 months.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Castration-Resistant Prostatic Cancer
Intervention  ICMJE
  • Drug: Niraparib
    Participants will receive niraparib 200 mg capsules once daily.
    Other Name: JNJ-64091742
  • Drug: Abiraterone Acetate
    Participants will receive AA 1000 mg tablets once daily.
  • Drug: Prednisone
    Participants will receive prednisone 10 mg tablets daily.
  • Drug: Placebo
    Participants will receive matching placebo once daily.
  • Drug: New Formulation of Niraparib and Abiraterone Acetate (AA)
    Participants will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets once daily.
Study Arms  ICMJE
  • Experimental: Cohort 1: Participants with mCRPC and HRR gene alteration
    Participants with L1 metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alteration will receive combination of niraparib 200 milligrams (mg) or matching placebo and abiraterone acetate (AA) 1000 mg plus prednisone 10 mg.
    Interventions:
    • Drug: Niraparib
    • Drug: Abiraterone Acetate
    • Drug: Prednisone
    • Drug: Placebo
  • Experimental: Cohort 2: Participants with mCRPC and No HRR Gene alteration
    Participants with L1 mCRPC and no HRR Gene alteration will receive combination of niraparib 200 mg or matching placebo and AA 1000 mg plus prednisone 10 mg.
    Interventions:
    • Drug: Niraparib
    • Drug: Abiraterone Acetate
    • Drug: Prednisone
    • Drug: Placebo
  • Experimental: Cohort 3 (Open-label): Participants with mCRPC
    Participants with mCRPC will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets plus prednisone 10 mg.
    Interventions:
    • Drug: Prednisone
    • Drug: New Formulation of Niraparib and Abiraterone Acetate (AA)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 19, 2018)
1000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 25, 2025
Estimated Primary Completion Date July 21, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • HRR gene alteration (as identified by the sponsor's required assays) as follows:

    1. Cohort 1: positive for HRR gene alteration
    2. Cohort 2: not positive for DRD (that is, HRR gene alteration)
  • Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI)
  • Metastatic prostate cancer in the setting of castrate levels of testosterone less than or equal to (<=) 50 nanogram per deciliter (ng/dL) on a gonadotropin releasing hormone analog (GnRHa) or bilateral orchiectomy
  • Able to continue GnRHa during the study if not surgically castrate
  • Score of <= 3 on the brief pain inventory-short form (BPI-SF) question number 3 (worst pain in last 24 hours)

Exclusion Criteria:

  • Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor
  • Systemic therapy (that is, novel second-generation AR-targeted therapy such as enzalutamide, apalutamide, or darolutamide; taxane-based chemotherapy, or more than 4 months of abiraterone acetate plus prednisone [AAP] prior to randomization) in the metastatic castration-resistant prostate cancer (mCRPC) setting; or AAP outside of the mCRPC setting
  • Symptomatic brain metastases
  • History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
  • Other prior malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) <= 2 years prior to randomization, or malignancy that currently requires active systemic therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   China,   Czechia,   France,   Germany,   Hungary,   Israel,   Italy,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   Poland,   Portugal,   Puerto Rico,   Russian Federation,   South Africa,   Spain,   Sweden,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03748641
Other Study ID Numbers  ICMJE CR108534
2017-003364-12 ( EudraCT Number )
64091742PCR3001 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee Yes
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  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP