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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 : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to evaluate the effectiveness of niraparib in combination with abiraterone acetate and prednisone (AA-P) compared to AA-P plus placebo.

Condition or disease Intervention/treatment Phase
Metastatic Prostate Cancer Drug: Niraparib Drug: Abiraterone Acetate Drug: Prednisone Drug: Placebo Phase 3

Detailed Description:
This study will assess efficacy and safety of niraparib in combination with AA-P for the treatment of participants with metastatic 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 17α-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 gene defects (DRD) 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 double-blind treatment phase, and a follow up phase. During the prescreening phase participants will be evaluated for DRD 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 up to 73 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 in Subjects With Metastatic Prostate Cancer
Actual Study Start Date : January 25, 2019
Estimated Primary Completion Date : July 21, 2022
Estimated Study Completion Date : February 25, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Niraparib + Abiraterone Acetate-Prednisone (AA-P)
Participants will receive oral administration of niraparib 200 milligram (mg) (2 capsules of 100 mg each) in combination with abiraterone acetate (AA) 1000 mg (4 tablets of 250 mg each) tablets and prednisone 10 mg (2 tablets of 5 mg each) tablets daily in each cycle (each cycle of 28 days).
Drug: Niraparib
Participants will receive niraparib 200 mg (2 capsules of 100 mg each) capsules once daily.
Other Name: JNJ-64091742

Drug: Abiraterone Acetate
Participants will receive abiraterone acetate 1000 mg (4 tablets of 250 mg each) tablets once daily.

Drug: Prednisone
Participants will receive prednisone 10 mg (2 tablets of 5 mg each) tablets daily.

Experimental: Placebo + AA-P
Participants will receive oral administration of matching placebo capsules in combination with AA 1000 mg (4 tablets of 250 mg each) tablets and prednisone 10 mg (2 tablets of 5 mg each) tablets daily in each cycle (each cycle of 28 days).
Drug: Abiraterone Acetate
Participants will receive abiraterone acetate 1000 mg (4 tablets of 250 mg each) tablets once daily.

Drug: Prednisone
Participants will receive prednisone 10 mg (2 tablets of 5 mg each) tablets daily.

Drug: Placebo
Participants will receive matching placebo capsules once daily.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Deoxyribonucleic acid (DNA)-repair gene defects (DRD) status (as identified by the sponsor's required assays) as follows:

    1. Cohort 1: positive for DRD
    2. Cohort 2: not positive for DRD (i.e. No DRD)
  • Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI)
  • Progression of 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 history of bilateral orchiectomy at study entry as evidenced by prostate-specific antigen (PSA) progression or radiographic progression
  • 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 (example, enzalutamide, docetaxel) in the metastatic castration-resistant prostate cancer (mCRPC) setting with the exception of less than 4 months of abiraterone acetate-Prednisone (AA-P) prior to randomization
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03748641


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03748641     History of Changes
Other Study ID Numbers: CR108534
2017-003364-12 ( EudraCT Number )
64091742PCR3001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: November 21, 2018    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Abiraterone Acetate
Niraparib
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors