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Trial record 1 of 1 for:    JANSSEN 64091742PCR2002
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A Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer (QUEST)

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ClinicalTrials.gov Identifier: NCT03431350
Recruitment Status : Recruiting
First Posted : February 13, 2018
Last Update Posted : April 10, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to: a) establish the recommended phase 2 dose (RP2D) and to evaluate the antitumor activity and safety of niraparib combination therapies (Combinations 1 and 2) and b) to determine the relative bioavailability of niraparib and abiraterone acetate (AA) in combination (Combination 3) in participants with metastatic castration-resistant prostate cancer (mCRPC).

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms, Castration-Resistant Drug: Niraparib 200 mg Drug: Cetrelimab 240 mg Drug: Cetrelimab 480 mg Drug: Abiraterone acetate 1000 mg Drug: Prednisone 5 mg Phase 1 Phase 2

Detailed Description:
This multicenter study will evaluate safety and efficacy of niraparib in combination with other anti-cancer agents. Combination 1 will combine niraparib with the anti-programmed cell death protein (PD)-1 monoclonal antibody cetrelimab, in participants with mCRPC. Combination 1 has 2 parts: in Part 1 (dose selection), participants will be enrolled to establish RP2D doses of niraparib and cetrelimab; and Part 2 (dose expansion) will evaluate the combination therapy in an expanded number of participants into 2 cohorts (biomarker positive or biomarker negative). Combination 2 is closed to enrollment. Combination 3 will evaluate the relative bioavailability (BA) of niraparib and AA in combination. In pharmacokinetics (PK) assessment phase niraparib will be administered in combination with AA and in extension phase niraparib plus AA will be administered in combination with prednisone. Combinations 1 and 2 will have 4 phases: A Pre-screening Phase, a Screening Phase, a Treatment Phase, and a Follow-up Phase; Combination 3 has 3 phases: A Screening Phase, A PK Assessment Phase, and an Extension Phase. Study evaluations will include efficacy, PK, PK/pharmacodynamics, biomarkers, safety and tolerability.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 148 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b-2 Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Actual Study Start Date : March 2, 2018
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
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.
Drug: Niraparib 200 mg
Participants will receive niraparib 200 mg orally.

Drug: Cetrelimab 240 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

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 [-]) and will receive established RP2D of cetrelimab and niraparib, in Part 2 until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. 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 is less than predetermined response rate as outlined in the protocol.
Drug: Niraparib 200 mg
Participants will receive niraparib 200 mg orally.

Drug: Cetrelimab 480 mg
Participants will receive cetrelimab 480 mg IV every 4 weeks.
Other Name: JNJ-63723283

Experimental: Combination 3: Niraparib + AA + prednisone
Participants will be assigned to one of the three cohorts to receive niraparib plus AA and prednisone as oral tablets.
Drug: Niraparib 200 mg
Participants will receive niraparib 200 mg orally.

Drug: Abiraterone acetate 1000 mg
Participants will receive oral tablets comprising 1000 mg AA.

Drug: Prednisone 5 mg
Participants will receive prednisone 5 mg tablets orally.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Combination 3: Maximum Observed Analyte Plasma Concentration (Cmax) of Niraparib and AA After a Single Dose [ Time Frame: Up to 168 hours postdose ]
    Cmax is defined as the maximum observed plasma concentration.

  6. Combination 3: Maximum Observed Analyte Plasma Concentration for Niraparib Normalized by the Dose (Cmax/dose) of Niraparib and AA After a Single Dose [ Time Frame: Up to 168 hours postdose ]
    Cmax/dose is defined as maximum observed analyte plasma concentration for niraparib normalized by the dose.

  7. Combination 3: Area Under the Plasma Concentration-Time Curve from Time Zero to 168 Hours (AUC [0-168]) of Niraparib and AA After a Single Dose [ Time Frame: Up to 168 hours postdose ]
    AUC (0-168) is defined as area under plasma concentration-time curve from time 0 to time 168 hours post dosing.

  8. Combination 3: Area Under the Plasma Concentration-Time Curve for Niraparib from Time Zero to 168 Hours (AUC [0-168]/dose) of Niraparib and AA After a Single Dose [ Time Frame: Up to 168 hours postdose ]
    AUC (0-168)/dose is defined as area under plasma concentration-time curve for niraparib from time 0 to time 168 hours post dosing.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Combination 3: Number of Participants with Adverse Events [ Time Frame: Up to 24 months ]
    Number of participants with adverse events will be reported.

  8. Combination 3: Number of Participants with Abnormal Clinical Laboratory Findings [ Time Frame: Up to 24 months ]
    Number of participants with abnormal clinical laboratory findings (hematology and serum chemistry) will be reported.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 for Combinations 1 and 2:

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

Inclusion Criteria for Combination 1A:

  • Must have determination of biomarker (BM) positive by the sponsor's blood or tissue assay, or a previous local test result (from a Clinical Laboratory Improvement Amendments [CLIA]-certified or equivalent laboratory) and reviewed by the sponsor to confirm eligibility
  • 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

Inclusion Criteria for Combination 1B:

- Combination 1B is closed to enrollment

Inclusion Criteria for Combination 2:

- Combination 2 is closed to enrollment

Inclusion Criteria for Combination 3:

- Diagnosed with mCRPC, who in the opinion of the investigator may benefit from treatment in Combination 3 of this study

Exclusion Criteria:

  • History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
  • Active malignancies (that is, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: non-muscle invasive bladder cancer; skin cancer (non-melanoma or melanoma); breast cancer; malignancy that is considered cured with minimal risk of recurrence
  • Active infection requiring systemic therapy
  • Allergies, hypersensitivity, or intolerance to niraparib or the corresponding excipients

Combination 1:

  • Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor
  • Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody
  • Active autoimmune disease

Combination 3:

  • Symptomatic brain metastases
  • Prior disease progression during combination treatment with AA and PARPi. Prior discontinuation of treatment with AA or PARPi due to AA- or PARPi-related toxicity

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): NCT03431350


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

Locations
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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: NCT03431350    
Other Study ID Numbers: CR108406
64091742PCR2002 ( Other Identifier: Janssen Research & Development, LLC )
2017-003552-23 ( EudraCT Number )
First Posted: February 13, 2018    Key Record Dates
Last Update Posted: April 10, 2020
Last Verified: April 2020

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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
Prostatic Neoplasms, Castration-Resistant
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