Clinical Trial: NCT03431350 - My Cancer Genome

NCT03431350

Description:

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).

Related Conditions:

Prostate Adenocarcinoma

Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT03431350

Trial Eligibility

Document

Title

Brief Title: A Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Official Title: A Phase 1b-2 Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer

Clinical Trial IDs

ORG STUDY ID: CR108406
SECONDARY ID: 64091742PCR2002
SECONDARY ID: 2017-003552-23
NCT ID: NCT03431350

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

Drug	Synonyms	Arms
Niraparib 200 mg		Combination 1:Dose Expansion: Niraparib + cetrelimab (Part 2)
Cetrelimab 240 mg	JNJ-63723283	Combination 1:Dose Selection: Niraparib + cetrelimab (Part 1)
Cetrelimab 480 mg	JNJ-63723283	Combination 1:Dose Expansion: Niraparib + cetrelimab (Part 2)
Abiraterone acetate 1000 mg		Combination 2: Dose Expansion: Niraparib + AA-P (Part 2)
Prednisone 5 mg		Combination 2: Dose Expansion: Niraparib + AA-P (Part 2)

Purpose

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 will combine niraparib with abiraterone acetate plus prednisone
      (AA-P) in mCRPC participants with DNA-repair gene defects (DRD). Combination 3 will evaluate
      the relative bioavailability (BA) of niraparib and AA in combination. In a pharmacokinetics
      (PK) assessment phase, niraparib and AA will be administered, and in an extension phase,
      niraparib and AA-P will be administered. 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.

Trial Arms

Name	Type	Description	Interventions
Combination 1:Dose Selection: Niraparib + cetrelimab (Part 1)	Experimental	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.	Niraparib 200 mg Cetrelimab 240 mg Cetrelimab 480 mg
Combination 1:Dose Expansion: Niraparib + cetrelimab (Part 2)	Experimental	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.	Niraparib 200 mg Cetrelimab 480 mg
Combination 2: Dose Expansion: Niraparib + AA-P (Part 2)	Experimental	Participants will be assigned to one of 4 cohorts based on biomarker status - Cohort 2A (BRCA biallelic loss), 2B (other DRD biallelic loss), 2C (BRCA monoallelic loss), or 2D (other DRD monoallelic loss), and will receive niraparib 200 mg once daily in combination with abiraterone acetate 1000 mg (4*250 mg) plus 10 mg prednisone (5 mg twice daily) throughout treatment phase.	Niraparib 200 mg Abiraterone acetate 1000 mg Prednisone 5 mg
Combination 3: Niraparib + AA-P	Experimental	Participants will be assigned to one of three cohorts to receive AA-P with or without niraparib.	Niraparib 200 mg Abiraterone acetate 1000 mg Prednisone 5 mg

Eligibility Criteria

        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

          -  Able to continue gonadotropin releasing hormone analogue (GnRHa) therapy during the
             study if not surgically castrate (that is, subjects who has not undergone bilateral
             orchiectomy).

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal
             to (<=) 1

          -  Toxicity associated with prior chemotherapy or radiotherapy has resolved to Grade <= 1
             (except alopecia or Grade <= 2 neuropathy) at screening

          -  Participant must agree not to donate sperm while on study treatment, and for 3 months
             following the last dose of study treatment

        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 3:

          -  Symptomatic brain metastases

          -  Prior disease progression during combination treatment with AA and poly (adenosine
             diphosphate [ADP]-ribose) polymerase inhibitor (PARPi). Prior discontinuation of
             treatment with AA or PARPi due to AA- or PARPi-related toxicity

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	Male
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Part 1: Combination 1: Incidence of Specified Toxicities
Time Frame:	Up to Day 28
Safety Issue:
Description:	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.

Secondary Outcome Measures

Measure:	Part 2: Combination 1: Number of Participants with Circulating Tumor Cell (CTC) Response
Time Frame:	Up to 42 months
Safety Issue:
Description:	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.

Measure:	Part 2: Combination 1: Composite Response Rate (RR)
Time Frame:	Up to 42 months
Safety Issue:
Description:	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.

Measure:	Part 2: Combination 1: Duration of Objective Response
Time Frame:	Up to 42 months
Safety Issue:
Description:	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.

Measure:	Part 2: Combination 1: Overall Survival (OS)
Time Frame:	Up to 46 months
Safety Issue:
Description:	OS is defined as time from start of treatment to death from any cause.

Measure:	Part 2: Combination 2: Objective Response Rate (ORR)
Time Frame:	Up to 42 months
Safety Issue:
Description:	ORR of soft tissue (visceral or nodal disease) as defined by RECIST 1.1 with no evidence of bone progression according to PCWG3 criteria. As per RECIST 1.1 criteria, ORR 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.

Measure:	Combination 3: Number of Participants with Adverse Events
Time Frame:	Up to 46 months
Safety Issue:
Description:	Number of participants with adverse events will be reported.

Measure:	Combination 3: Number of Participants with Abnormal Clinical Laboratory Findings
Time Frame:	Up to 46 months
Safety Issue:
Description:	Number of participants with abnormal clinical laboratory findings (hematology and serum chemistry) will be reported.

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Janssen Research & Development, LLC

Last Updated

July 19, 2021

Clinical Trials /

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