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A Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer (QUEST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03431350
Recruitment Status : Recruiting
First Posted : February 13, 2018
Last Update Posted : January 31, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE February 6, 2018
First Posted Date  ICMJE February 13, 2018
Last Update Posted Date January 31, 2020
Actual Study Start Date  ICMJE March 2, 2018
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2020)
  • Part 1: Combination 1: Incidence of Specified Toxicities [ Time Frame: Up to 28 days ]
    Incidence defined as number of participants with specified toxicities will be reported. The dose will be considered intolerable if a participant developed Grade greater than or equal to (>=) 3 non-hematological toxicity (with exceptions including anorexia, fever, constipation, fatigue that improves to Grade less than or equal to (<=) 2 in <=7 days, vomiting and diarrhea that resolves in <=3 days with best supportive care), treatment-related Grade 4 thrombocytopenia or Grade >= 3 thrombocytopenia, treatment-related Grade 4 neutropenia >= 7 days, or Grade 3 or 4 neutropenia, treatment-related serious adverse events.
  • Part 2: Combination 1: Objective Response Rate (ORR) [ Time Frame: Approximately 24 months ]
    Objective response rate is defined as the percentage of participants who achieve complete response (CR) or partial response (PR), as assessed by response evaluation criteria in solid tumors (RECIST) 1.1 criteria with no evidence of bone progression according to prostate cancer working group 3 (PCWG3) criteria.
  • Part 2: Combinations 1: Incidence of Adverse Events (AEs) [ Time Frame: Approximately 24 months ]
    Incidence defined as number of participants with AEs will be reported. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
  • Part 2: Combinations 1: Severity of Adverse Events [ Time Frame: Approximately 24 months ]
    Any AE not listed in the NCI-CTCAE will be graded according to the investigator's clinical judgment using the standard grades.
Original Primary Outcome Measures  ICMJE
 (submitted: February 6, 2018)
  • Part 1: Incidence of Specified Toxicities [ Time Frame: Up to 28 days ]
    Incidence defined as number of participants with specified toxicities will be reported. The dose will be considered intolerable if a participant developed Grade greater than or equal to (>=) 3 non-hematological toxicity (with exceptions including anorexia, fever, constipation, fatigue that improves to Grade less than or equal to (<=) 2 in <=7 days, vomiting and diarrhea that resolves in <=3 days with best supportive care), treatment-related Grade 4 thrombocytopenia or Grade >= 3 thrombocytopenia, treatment-related Grade 4 neutropenia >= 7 days, or Grade 3 or 4 neutropenia, treatment-related serious adverse events.
  • Part 2: Objective Response Rate (ORR) [ Time Frame: Approximately 24 months ]
    Objective response rate is defined as the percentage of participants who achieve complete response (CR) or partial response (PR), as assessed by response evaluation criteria in solid tumors (RECIST) 1.1 criteria with no evidence of bone progression according to prostate cancer working group 3 (PCWG3) criteria. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the baseline sum diameters.
  • Part 2: Incidence of Adverse Events (AEs) [ Time Frame: Approximately 24 months ]
    Incidence defined as number of participants with AEs will be reported. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
  • Part 2: Severity of Adverse Events [ Time Frame: Approximately 24 months ]
    An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Severity of AEs will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Any AE not listed in the NCI-CTCAE will be graded according to the investigator's clinical judgment using the standard grades as follows: Grade 1 (Mild): Awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities; Grade 2 (Moderate): Sufficient discomfort is present to cause interference with normal activity; Grade 3 (Severe): Extreme distress, causing significant impairment of functioning or incapacitation. Prevents normal everyday activities; Grade 4, Life-threatening: Urgent intervention indicated; Grade 5, Death: Death.
Change History Complete list of historical versions of study NCT03431350 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2020)
  • Part 1 and Part 2 (Combination 1): Plasma Concentrations of Niraparib and Cetrelimab [ Time Frame: Cycle 1 up to 12 (each cycle is of 28 days) ]
    Plasma concentrations of niraparib and cetrelimab will be assessed.
  • Part 1 and Part 2 (Combination 1): Number of participants with Anti-Drug Antibodies [ Time Frame: Approximately 24 months ]
    Number of participants with Anti-Drug Antibodies will be reported.
  • Part 2: Combination 1: Number of Participants with Circulating Tumor Cell (CTC) Response [ Time Frame: From screening up to end of treatment (30 days of last dose) (approximately up to 24 months) ]
    CTC response is defined as CTC=0 per 7.5 milliliter (mL) of blood at 8 weeks for participants who have CTC >= 1 at baseline or CTC<5 per 7.5 mL with CTC >=5 at baseline, confirmed by a second consecutive value obtained 4 or more weeks later.
  • Part 2: Combination 1: Composite Response Rate (RR) [ Time Frame: Screening, Cycle 1 (each cycle of 28 days) Day 1 (every 8 weeks for the first 6 months and then every 12 weeks thereafter) until follow-up phase (for 3 months) (approximately up to 24 months) ]
    Composite RR is defined as percentage of participants who have 1 of the following by PCWG3: Objective response (confirmed per RECIST 1.1), or CTC response: defined as CTC=0 per 7.5 mL of blood at 8 weeks for participants who have CTC >=1 at baseline or CTC <5 baseline per 7.5 mL with CTC>5 at baseline, confirmed by a second consecutive value obtained 4 or more weeks later, or PSA decline of >= 50%, measured twice 3 to 4 weeks apart.
  • Part 2: Combination 1: Duration of Objective Response [ Time Frame: Screening, Cycle 1 (each cycle of 28 days) Day 1 (every 8 weeks for the first 6 months and then every 12 weeks thereafter) until follow-up phase (approximately up to 24 months) ]
    Duration of objective response is defined as time from complete response (CR) or partial response (PR) to radiographic progression of disease (PD), unequivocal clinical progression, or death, whichever occurs first. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 % decrease in sum of the diameters of the target lesions taking as reference the baseline sum diameters. PD is defined as a 20% increase in the sum of diameters of all target lesions and a minimum absolute increase of 5 mm in the sum.
  • Part 2: Combination 1: Overall Survival (OS) [ Time Frame: Up to follow-up (approximately up to 24 months) ]
    OS is defined as time from start of treatment to death from any cause.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2018)
  • Part 1 and Part 2: Plasma Concentrations of Niraparib and JNJ-63723283 [ Time Frame: Cycle 1 up to 12 (each cycle is of 28 days) ]
    Plasma concentrations of niraparib and JNJ-63723283 will be assessed.
  • Part 1 and Part 2: Number of participants with Anti-Drug Antibodies [ Time Frame: Approximately 24 months ]
    Number of participants with Anti-Drug Antibodies will be reported.
  • Part 2: Number of Participants with Circulating Tumor Cell (CTC) Response [ Time Frame: From screening up to end of treatment (30 days of last dose) (approximately up to 24 months) ]
    CTC response is defined as CTC=0 per 7.5 milliliter (mL) of blood at 8 weeks for participants who have CTC >= 1 at baseline.
  • Part 2: Response Rate (RR) [ Time Frame: Screening, Cycle 1 (each cycle of 28 days) Day 1 (every 8 weeks for the first 6 months and then every 12 weeks thereafter) until follow-up phase (for 3 months) (approximately up to 24 months) ]
    RR is defined as one of Objective response (confirmed per RECIST 1.1), or Conversion of CTC from >= 5 cells per 7.5 mL blood at baseline to less than (<) 5 cells per 7.5 mL blood nadir, confirmed by a second consecutive value obtained 4 or more weeks later, or prostate-specific antigen (PSA) decline of >= 50 %, measured twice 3 to 4 weeks apart.
  • Part 2: Duration of Objective Response [ Time Frame: Screening, Cycle 1 (each cycle of 28 days) Day 1 (every 8 weeks for the first 6 months and then every 12 weeks thereafter) until follow-up phase (approximately up to 24 months) ]
    Duration of objective response is defined as time from complete response (CR) or partial response (PR) to radiographic progression of disease (PD), unequivocal clinical progression, or death, whichever occurs first. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 % decrease in sum of the diameters of the target lesions taking as reference the baseline sum diameters. PD is defined as a 20% increase in the sum of diameters of all target lesions and a minimum absolute increase of 5 mm in the sum.
  • Part 2: Overall Survival (OS) [ Time Frame: Up to follow-up (approximately up to 24 months) ]
    OS is defined as time from enrollment to death from any cause.
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 Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Official Title  ICMJE A Phase 1b-2 Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Brief Summary The purpose of this study is to establish the recommended phase 2 dose (RP2D) of niraparib combination therapies of Part 1 and to evaluate the antitumor activity and safety of niraparib combination therapies of Part 2.
Detailed Description This multicenter study will evaluate safety and efficacy of niraparib in combination with other anti-cancer agents. Combination 1 is being studied that will combine niraparib with the anti-programmed cell death protein (PD)-1 monoclonal antibody, cetrelimab in participants with metastatic castration-resistant prostate cancer (mCRPC). Combination 1 has 2 parts: in Part 1 (dose selection), participants will be enrolled to explore 2 doses of niraparib and cetrelimab; and Part 2 (dose expansion) will evaluate the combination therapy in an expanded number of participants (who are either BM+ or BM- for DRD or BM+ for CDK12). In Part 2, participants will be enrolled into 2 cohorts based on biomarker status. Each combination in the study will have 4 phases: A Prescreening Phase, a Screening Phase, a Treatment Phase, and a Follow-up Phase. Study evaluations will include efficacy, pharmacokinetic (PK), PK/pharmacodynamics, biomarkers, safety and tolerability.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostatic Neoplasms, Castration-Resistant
Intervention  ICMJE
  • Drug: Niraparib 200 mg
    Participant will receive niraparib 200 mg orally once daily.
  • Drug: Cetrelimab mg
    Participants will receive cetrelimab 240 mg IV every 2 weeks.
    Other Name: JNJ-63723283
  • Drug: Cetrelimab 480 mg
    Participants will receive cetrelimab 480 mg IV every 4 weeks.
    Other Name: JNJ-63723283
Study Arms  ICMJE
  • Experimental: Combination 1:Dose Selection: Niraparib + cetrelimab(Part 1)
    Dose regimen 1: The participants will receive niraparib 200 milligram (mg) orally once daily in combination with cetrelimab 240 mg intravenously (IV) once every 2 weeks. Dose regimen 2: The participants will receive niraparib 200 mg orally once daily in combination with cetrelimab 480 mg IV once every 4 weeks in 28-day treatment cycles until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. The safety evaluation team (SET) will determine if an additional cohort is necessary, based on the data from dose regimens 1 and 2.
    Interventions:
    • Drug: Niraparib 200 mg
    • Drug: Cetrelimab mg
    • Drug: Cetrelimab 480 mg
  • Experimental: Combination 1:Dose Expansion: Niraparib + cetrelimab(Part 2)
    Participants will be assigned to either Cohort 1A (Biomarker [BM] positive [+]) or Cohort 1B (BM negative [-]) for DRD or BM+ for CDK12 (Cohort 1A) and will receive 480 mg of cetrelimab IV once every 4 weeks and niraparib 200 mg once daily as RP2D, in Part 2. A futility analysis will be performed for the Cohort 1B after 10 BM- participants are enrolled in Part 2. This cohort will be closed if the response rate is 13 percent (%) or less for the participants.
    Interventions:
    • Drug: Niraparib 200 mg
    • Drug: Cetrelimab 480 mg
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: January 30, 2020)
80
Original Estimated Enrollment  ICMJE
 (submitted: February 6, 2018)
60
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants willing to undergo all protocol-specified biopsies
  • Diagnosis of prostate adenocarcinoma as confirmed by the investigator

Combination 1:

  • Must have determination of biomarker (BM) positive for DNA-repair gene defects (DRD) or CDK12 (biallelic) by the sponsor's blood or tissue assay
  • Participants must have measurable disease as defined by response evaluation criteria in solid tumors (RECIST) 1.1 (soft tissue lesion of greater than or equal to (>=) 10 millimeter (mm) in the long axis or extrapelvic lymph node of >=15 mm in the short axis)
  • Must have previously received at least 1, but no more than 2, lines of novel androgen receptor (AR)-targeted therapy (that is, abiraterone acetate with prednisone, enzalutamide) for metastatic castration-resistant prostate cancer (mCRPC). Participants must have had at least 4 weeks of AR-targeted therapy

Combination 2:

- Combination 2 is closed to enrollment

Exclusion Criteria:

  • Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor
  • History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
  • Active malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently remission) less than or equal to (<=) 2 years prior to enrollment
  • Active infection requiring systemic therapy
  • Allergies, hypersensitivity, or intolerance to niraparib or the corresponding excipients
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 Belgium,   Canada,   France,   Israel,   Italy,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03431350
Other Study ID Numbers  ICMJE CR108406
64091742PCR2002 ( Other Identifier: Janssen Research & Development, LLC )
2017-003552-23 ( EudraCT Number )
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 January 2020

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