Study of the Efficacy, Safety and Pharmacokinetics of Pamiparib (BGB-290) in Participants With Advanced Solid Tumors
- Conditions
- Advanced High-grade Ovarian CancerTriple Negative Breast Cancer
- Interventions
- Registration Number
- NCT03333915
- Lead Sponsor
- BeiGene
- Brief Summary
This study is designed to evaluate the safety, tolerability, PKharmacokinetic profile and treatment effect of pamiparib in Chinese participants with advanced high-grade ovarian cancer (including fallopian cancer or primary peritoneal cancer) and triple negative breast cancer in phase I, and to evaluate the efficacy and safety of pamiparib in Chinese participants with recurrent epithelial ovarian cancer (including fallopian cancer or primary peritoneal cancer), harboring germline breast cancer susceptibility gene 1/gene 2 (BRCA1/2) mutation in phase II.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 128
- Participants have voluntarily agreed to participate by giving written informed consent.
- Age 18 years (including 18 years) on the day of signing informed consent.
- Participants meet the following eligibility criteria for the corresponding part of the study: 1) In Phase 1 portion: The participants must have a histologically or cytologically confirmed locally advanced or metastatic cancer, either triple-negative breast cancer or epithelial, non-mucinous, high-grade ovarian cancer (including fallopian cancer, or primary peritoneal cancer), for which no effective standard therapy is available.
- In Phase 2 portion: Participants who have histologically or cytologically confirmed high-grade epithelial ovarian cancer (including fallopian cancer or primary peritoneal cancer), harboring germline BRCA1/2 mutation 4. Participants must have measurable disease as defined per the RECIST, version 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
Key
- Participants who have been treated with chemotherapy, biologic therapy, immunotherapy, investigational agent, anti-cancer Chinese medicine, or anticancer herbal remedies ≤ 14 days (or ≤5 half-lives, whichever is shorter) prior to starting study drug, or who have not adequately recovered from the side effects of such therapy.
- Participants who have undergone major surgery for any cause ≤ 4 weeks prior to starting study drug. Participants must have adequately recovered from the previous treatment and have a stable clinical condition before entering the study.
- Participants who have undergone radiotherapy for any cause ≤ 14 days prior to starting study drug. Participants must have adequately recovered from the previous treatment and have a stable clinical condition before entering the study.
- Untreated and/or active brain metastases.
- Prior therapies targeting poly (ADP-ribose) polymerase (PARP).
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase 1: 20 milligram (mg) pamiparib Pamiparib 20 mg pamiparib twice a day for 21 days Phase 1 : 40 mg pamiparib Pamiparib 40 mg pamiparib twice a day for 21 days 60 mg pamiparib in platinum-sensitive ovarian cancer (PSOC) Pamiparib 60 mg pamiparib twice a day until occurrence of unacceptable toxicities, disease progression, withdrawal of consent or investigator discretion 60 mg pamiparib in platinum resistant ovarian cancer (PROC) Pamiparib 60 mg pamiparib twice a day until occurrence of unacceptable toxicities, disease progression, withdrawal of consent or investigator discretion 60 mg pamiparib Pamiparib 60 mg pamiparib twice a day for 21 days
- Primary Outcome Measures
Name Time Method Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) From first dose to within 30 days of last dose of pamiparib (approximately 36 months) A TEAE is defined as an adverse event (AE) that had an onset date on or after the first dose of study drug up to 30 days following study drug discontinuation or was worsening in severity from baseline (pretreatment).
Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs) From first dose to within 30 days of last dose of pamiparib (approximately 36 months) Phase 2: Objective Response Rate (ORR) in High Grade Ovarian Cancer (HGOC) Both PSOC and PROC as Assessed by Independent Radiology Review Committee (IRC) Up to approximately 2 years and 8 months ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response
- Secondary Outcome Measures
Name Time Method Phase 2: Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC0-12) Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose Phase I: Maximum Observed Plasma Concentration (Cmax) Cycle 1 Day 1 and Day 10 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose Phase I: Time to Reach Cmax (Tmax) Cycle 1 Day 1 and Day 10 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose Phase I: Terminal Elimination Half-life (t1/2) Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose Phase I: Apparent Clearance (CL/F) Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose Phase I: Apparent Volume of Distribution During Terminal Phase (Vz/F) Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose Phase 2: Disease Control Rate by Investigator Per RECIST v1.1 Up to approximately 3 years and 8 months DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR and stable disease (SD)
Phase 2: Duration of Response as Assessed by Investigator Per RECIST v1.1 Up to approximately 3 years and 8 months DOR is defined as the time from the first determination of a confirmed overall response until the first documentation of progression or death, whichever comes first
Phase 1: Disease Control Rate (DCR) Assessed by the Investigator Per RECIST v1.1 Up to approximately 36 months DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR and stable disease (SD)
Phase I: Clinical Benefit Rate (CBR) Assessed by the Investigator Per RECIST v1.1 Up to approximately 36 months CBR is defined as percentage of participants with best overall response of CR, PR and stable disease (SD)≥24 weeks
Phase I : Progression Free Survival (PFS) Up to approximately 36 months PFS is defined as the time from first dose of study medication to the first documented disease progression or death due to any cause, whichever occurs first
Phase 2: Carcinoma Antigen-125 (C(A-125) Response Rate by Gynecologic Cancer Inter Group (GCIG )Criteria Up to approximately 3 years and 8 months CA-125 response is defined the percentage of participants with at least 50% reduction in CA-125 levels from pre-treatment sample
Phase 2: Number of Participants With Treatment- Emergent Adverse Events and Serious Adverse Events From first dose to within 30 days of last dose of pamiparib (approximately 3 years and 8 months) A TEAE is defined as an adverse event (AE) that had an onset date on or after the first dose of study drug up to 30 days following study drug discontinuation or was worsening in severity from baseline (pretreatment). All clinically significant abnormalities in physical examinations, laboratory tests and ECGs are reported as adverse events (AE) in the AE section.
Phase I: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator Per RECIST v1.1 Up to approximately 36 months ORR is defined as the percentage of participants with confirmed Complete Response (CR) or Partial Response (PR)
Phase 1: Duration of Response (DOR) as Assessed by Investigator Per RECIST v1.1 Up to approximately 36 months DOR is defined as the time from the first determination of a confirmed overall response until the first documentation of progression or death, whichever comes first
Phase 2: Objective Response Rate (ORR) by Investigator Per RECIST v1.1 Up to approximately 3 years and 8 months ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response
Phase 2: Clinical Benefit Rate by Investigator Per RECIST v1.1 Up to approximately 3 years and 8 months CBR is defined as percentage of participants with best overall response of CR, PR and stable disease (SD)≥24 weeks
Phase 2: Overall Survival (OS) as Assessed by Investigator Up to approximately 3 years and 8 months OS is defined as time from the first dose of study medication to the date of death due to any cause
Phase 2: Progression Free Survival as Assessed by the Investigator Per RECIST v1.1 Up to approximately 3 years and 8 months PFS is defined as the time from first dose of study medication to the first documented disease progression or death due to any cause, whichever occurs first
Phase 2: Maximum Observed Plasma Concentration (Cmax) Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose Phase 2: Time to Reach Cmax (Tmax) Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose Phase 2: Area Under the Plasma Concentration-time Curve From 0 to the 9 Hours Post-dose (AUC0-9) Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Trial Locations
- Locations (6)
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China