Clinical trial NCT03333915: Study of the Efficacy, Safety and Pharmacokinetics of Pamiparib (BGB-290) in Participants With Advanced Solid Tumors
Official title: An Open Label, Multi-Center Phase I/II Study to Evaluate Efficacy and Safety of BGB-290 in Chinese Subjects With Advanced Ovarian Cancer, Fallopian Cancer, and Primary Peritoneal Cancer or Advanced Triple Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced High-grade Ovarian Cancer
Triple Negative Breast Cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2017-11-07
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

1. Participants have voluntarily agreed to participate by giving written informed consent.
2. Age 18 years (including 18 years) on the day of signing informed consent.
3. 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.

2) 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.

5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1

Key Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Untreated and/or active brain metastases.
5. Prior therapies targeting poly (ADP-ribose) polymerase (PARP).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
timeFrame: From first dose to within 30 days of last dose of pamiparib (approximately 36 months)
measure: Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs)
timeFrame: From first dose to within 30 days of last dose of pamiparib (approximately 36 months)
measure: Phase 2: Objective Response Rate (ORR) in High Grade Ovarian Cancer (HGOC) Both PSOC and PROC as Assessed by Independent Radiology Review Committee (IRC)
timeFrame: Up to approximately 2 years and 8 months
Secondary outcomes:
measure: Phase I: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: Phase I: Time to Reach Cmax (Tmax)
timeFrame: 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
measure: Phase I: Terminal Elimination Half-life (t1/2)
timeFrame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
measure: Phase I: Apparent Clearance (CL/F)
timeFrame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
measure: Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)
timeFrame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
measure: Phase I: Apparent Volume of Distribution During Terminal Phase (Vz/F)
timeFrame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
measure: Phase I: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator Per RECIST v1.1
timeFrame: Up to approximately 36 months
measure: Phase 1: Disease Control Rate (DCR) Assessed by the Investigator Per RECIST v1.1
timeFrame: Up to approximately 36 months
measure: Phase I: Clinical Benefit Rate (CBR) Assessed by the Investigator Per RECIST v1.1
timeFrame: Up to approximately 36 months
measure: Phase 1: Duration of Response (DOR) as Assessed by Investigator Per RECIST v1.1
timeFrame: Up to approximately 36 months
measure: Phase I : Progression Free Survival (PFS)
timeFrame: Up to approximately 36 months
measure: Phase 2: Objective Response Rate (ORR) by Investigator Per RECIST v1.1
timeFrame: Up to approximately 3 years and 8 months
measure: Phase 2: Disease Control Rate by Investigator Per RECIST v1.1
timeFrame: Up to approximately 3 years and 8 months
measure: Phase 2: Clinical Benefit Rate by Investigator Per RECIST v1.1
timeFrame: Up to approximately 3 years and 8 months
measure: Phase 2: Carcinoma Antigen-125 (C(A-125) Response Rate by Gynecologic Cancer Inter Group (GCIG )Criteria
timeFrame: Up to approximately 3 years and 8 months
measure: Phase 2: Duration of Response as Assessed by Investigator Per RECIST v1.1
timeFrame: Up to approximately 3 years and 8 months
measure: Phase 2: Progression Free Survival as Assessed by the Investigator Per RECIST v1.1
timeFrame: Up to approximately 3 years and 8 months
measure: Phase 2: Overall Survival (OS) as Assessed by Investigator
timeFrame: Up to approximately 3 years and 8 months
measure: Phase 2: Number of Participants With Treatment- Emergent Adverse Events and Serious Adverse Events
timeFrame: From first dose to within 30 days of last dose of pamiparib (approximately 3 years and 8 months)
measure: Phase 2: Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC0-12)
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
measure: Phase 2: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
measure: Phase 2: Time to Reach Cmax (Tmax)
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
measure: Phase 2: Area Under the Plasma Concentration-time Curve From 0 to the 9 Hours Post-dose (AUC0-9)
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: BeiGene
name: Study Director
role: PRINCIPAL_INVESTIGATOR
References: