Study of the Efficacy, Safety and Pharmacokinetics of Pamiparib (BGB-290) in Participants With Advanced Solid Tumors

Triple Negative Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03333915
• Other study ID #: BGB-290-102
• Secondary ID: CTR20160828
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 21, 2016
• Est. completion date: August 11, 2021

Study information

• Verified date: July 2023
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: August 11, 2021
• Est. primary completion date: August 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced High-grade Ovarian Cancer
• Breast Neoplasms
• Carcinoma, Ovarian Epithelial
• Ovarian Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Pamiparib
Pamiparib is provided as oral capsules

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University People Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	The second Hospital of Jilin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	West China Hospital Sichuan University	Chengdu	Sichuan
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	The First Affiliated Hospital of Xian Jiaotong University	Dalian	Liaoning
China	The First Hospital of Dalian Medical University	Dalian	Liaoning
China	SUN YAT-SEN memorial hospital,SUN YAT-SEN University	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Cancer Hospital	Hefei	Anhui
China	The First Bethune Hospital of Jilin University	Jilin	Changchun
China	QILU Hospital of Shandong University	Jinan	Shandong
China	Jiangxi Maternal and Child Health Hospital	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Liaoning Cancer Hospital&Institute	Shenyang	Liaoning
China	Tianjin Medical University Cancer institute & Hospital	Tianjin	Tianjin
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)	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).	From first dose to within 30 days of last dose of pamiparib (approximately 36 months)
Primary	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)
Primary	Phase 2: Objective Response Rate (ORR) in High Grade Ovarian Cancer (HGOC) Both PSOC and PROC as Assessed by Independent Radiology Review Committee (IRC)	ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response	Up to approximately 2 years and 8 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Phase I: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator Per RECIST v1.1	ORR is defined as the percentage of participants with confirmed Complete Response (CR) or Partial Response (PR)	Up to approximately 36 months
Secondary	Phase 1: Disease Control Rate (DCR) Assessed by the Investigator Per RECIST v1.1	DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR and stable disease (SD)	Up to approximately 36 months
Secondary	Phase I: Clinical Benefit Rate (CBR) Assessed by the Investigator Per RECIST v1.1	CBR is defined as percentage of participants with best overall response of CR, PR and stable disease (SD)=24 weeks	Up to approximately 36 months
Secondary	Phase 1: Duration of Response (DOR) as Assessed by Investigator Per RECIST v1.1	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	Up to approximately 36 months
Secondary	Phase I : Progression Free Survival (PFS)	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	Up to approximately 36 months
Secondary	Phase 2: Objective Response Rate (ORR) by Investigator Per RECIST v1.1	ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response	Up to approximately 3 years and 8 months
Secondary	Phase 2: Disease Control Rate by Investigator Per RECIST v1.1	DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR and stable disease (SD)	Up to approximately 3 years and 8 months
Secondary	Phase 2: Clinical Benefit Rate by Investigator Per RECIST v1.1	CBR is defined as percentage of participants with best overall response of CR, PR and stable disease (SD)=24 weeks	Up to approximately 3 years and 8 months
Secondary	Phase 2: Carcinoma Antigen-125 (C(A-125) Response Rate by Gynecologic Cancer Inter Group (GCIG )Criteria	CA-125 response is defined the percentage of participants with at least 50% reduction in CA-125 levels from pre-treatment sample	Up to approximately 3 years and 8 months
Secondary	Phase 2: Duration of Response as Assessed by Investigator Per RECIST v1.1	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	Up to approximately 3 years and 8 months
Secondary	Phase 2: Progression Free Survival as Assessed by the Investigator Per RECIST v1.1	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	Up to approximately 3 years and 8 months
Secondary	Phase 2: Overall Survival (OS) as Assessed by Investigator	OS is defined as time from the first dose of study medication to the date of death due to any cause	Up to approximately 3 years and 8 months
Secondary	Phase 2: Number of Participants With Treatment- Emergent Adverse Events and Serious Adverse Events	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.	From first dose to within 30 days of last dose of pamiparib (approximately 3 years and 8 months)
Secondary	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
Secondary	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
Secondary	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
Secondary	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