Back to resultsA Study of Fluzoparib Given in Combination With Apatinib in Ovarian or Breast Cancer Patients
Primary Purpose
Ovarian Cancer, Triple Negative Breast Cancer
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Fluzoparib
Apatinib
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring PARP inhibitor, VEGFR inhibitor, Combination therapy, Ovarian Cancer, Triple Negative Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Life expectancy of more than 12 weeks.
- Histologically or cytologically confirmed high-grade papillary-serous epithelial ovarian cancer，primary peritoneal, or fallopian tube cancers; subjects with a known deleterious breast cancer gene (BRCA) mutation and any other high-grade histology are also eligible. Subjects should have platinum-sensitive disease, where platinum-sensitive disease is defined as having had a > 6 month interval since last receiving platinum therapy prior to disease recurrence. Additionally, subjects with histologically or cytologically confirmed triple negative breast cancer (TNBC）, that is locally advanced or metastatic, are also eligible.
- Prior therapy：subjects with ovarian cancer，primary peritoneal, or fallopian tube cancers have received only 2 lines of platinum-based chemotherapies, and TNBC patients have received only 1 line of standard chemotherapy. Each prior chemotherapy must be given for at least 2 cycles.
- At least one measurable lesion that can be accurately assessed by imaging (CT/MRI) at baseline
- Subjects who have overall good overall general condition.
- Signed informed consent.
Exclusion Criteria:
- Subjects who received any previous treatment with any PARP inhibitors.
- Subjects who received any previous treatment with any VEGFR inhibitors.
- Less than 4 weeks from the last clinical trial.
- Less than 4 weeks from the last radiotherapy, chemotherapy, surgery, hormone treatment and target therapy.
- Unstable or uncontrolled hypertension.
- Subjects that are unable to swallow, or dysfunction of gastrointestinal absorption.
- Subjects with brain metastases.
- Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry.
- Subjects with a known hypersensitivity to fluzoparib, apatinib or any of the excipients of the products.
- Ongoing infection (determined by investigator).
- History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation.
- Pregnant or breast-feeding women.
Sites / Locations
- Beijing Cancer Hosptial
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Fluzoparib + Apatinib
Arm Description
Fluzoparib and apatinib will be separately administered to patients on the 1st and 4th day, respectively. Then from the 7th day they are administered continuously and orally in combination, 28 days per cycle, until disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
The type and incidence of adverse events [safety and tolerability]
Adverse events defined according to Common Terminology for Adverse Events (CTCAE) v4.03
Secondary Outcome Measures
Objective Response Rate (ORR)
[Complete response + Partial response (CR+PR)] based on RECIST 1.1
Disease Control Rate (DOR)
[Complete response + Partial response + Stable disease (CR+PR+SD)] based on RECIST 1.1
Time to Progression (TTP)
The time from start of the treatment until radiographic disease progression or CA-125 progression specific for ovarian cancer patients
Overall Survival (OS)
Time from start of fluzoparib treatment until death due to any cause
Cmax
Maximum Plasma Concentration
T1/2 (Half-life)
The time required for the plasma concentration of a drug to be reduced by 50%
Area under curve (AUC)
Area under the plasma concentration-time curve
V/F
Volume of distribution
CL/F
Plasma Clearance
Full Information
NCT ID
NCT03075462
First Posted
March 6, 2017
Last Updated
June 30, 2022
Sponsor
Jiangsu HengRui Medicine Co., Ltd.
Collaborators
Peking University Cancer Hospital & Institute
1. Study Identification
Unique Protocol Identification Number
NCT03075462
Brief Title
A Study of Fluzoparib Given in Combination With Apatinib in Ovarian or Breast Cancer Patients
Official Title
An Open, Non-randomised, Multi-centre Phase I Study to Assess the Safety and Efficacy of Fluzoparib Given in Combination With Apatinib in Patients With Recurrent Ovarian Cancer or Triple Negative Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
March 9, 2017 (Actual)
Primary Completion Date
August 22, 2021 (Actual)
Study Completion Date
December 13, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu HengRui Medicine Co., Ltd.
Collaborators
Peking University Cancer Hospital & Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Fluzoparib is an oral potent, selective poly-ADP ribose polymerase-1 (PARP-1) and PARP-2 inhibitor; Apatinib is an oral selective vascular endothelial growth factor receptor (VEGFR) inhibitor. This open-label, dose finding phase I trial studies the tolerability and the best dose of fluzoparib in combination with apatinib and to see how well these two drugs work together in the treatment of patients with recurrent ovarian cancer or triple negative breast cancer. The safety and efficacy of fluzoparib in combination with apatinib will be explored. Both dose escalation and dose expansion parts are included in this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Triple Negative Breast Cancer
Keywords
PARP inhibitor, VEGFR inhibitor, Combination therapy, Ovarian Cancer, Triple Negative Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
98 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fluzoparib + Apatinib
Arm Type
Experimental
Arm Description
Fluzoparib and apatinib will be separately administered to patients on the 1st and 4th day, respectively. Then from the 7th day they are administered continuously and orally in combination, 28 days per cycle, until disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Fluzoparib
Other Intervention Name(s)
SHR3162, HS10160
Intervention Description
Fluzoparib either at 40,60,80mg twice daily,capsule oral.
Intervention Type
Drug
Intervention Name(s)
Apatinib
Intervention Description
Apatinib at 250mg once daily, tablet oral
Primary Outcome Measure Information:
Title
The type and incidence of adverse events [safety and tolerability]
Description
Adverse events defined according to Common Terminology for Adverse Events (CTCAE) v4.03
Time Frame
From screening up to 28 days after end of treatment
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
[Complete response + Partial response (CR+PR)] based on RECIST 1.1
Time Frame
24 months (approx) from the start of treatment
Title
Disease Control Rate (DOR)
Description
[Complete response + Partial response + Stable disease (CR+PR+SD)] based on RECIST 1.1
Time Frame
24 months (approx) from the start of treatment
Title
Time to Progression (TTP)
Description
The time from start of the treatment until radiographic disease progression or CA-125 progression specific for ovarian cancer patients
Time Frame
From date of enrollment until the date of first objective progression or CA-125 progression (only for ovarian cancer patients), assessed up to 36 months
Title
Overall Survival (OS)
Description
Time from start of fluzoparib treatment until death due to any cause
Time Frame
From Cycle 1, Day 1 until death or up to 48 months (approx)
Title
Cmax
Description
Maximum Plasma Concentration
Time Frame
From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment
Title
T1/2 (Half-life)
Description
The time required for the plasma concentration of a drug to be reduced by 50%
Time Frame
From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment
Title
Area under curve (AUC)
Description
Area under the plasma concentration-time curve
Time Frame
Within the first 5 weeks from start of fluzoparib treatment
Title
V/F
Description
Volume of distribution
Time Frame
From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment
Title
CL/F
Description
Plasma Clearance
Time Frame
From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Life expectancy of more than 12 weeks.
Histologically or cytologically confirmed high-grade papillary-serous epithelial ovarian cancer，primary peritoneal, or fallopian tube cancers; subjects with a known deleterious breast cancer gene (BRCA) mutation and any other high-grade histology are also eligible. Subjects should have platinum-sensitive disease, where platinum-sensitive disease is defined as having had a > 6 month interval since last receiving platinum therapy prior to disease recurrence. Additionally, subjects with histologically or cytologically confirmed triple negative breast cancer (TNBC）, that is locally advanced or metastatic, are also eligible.
Prior therapy：subjects with ovarian cancer，primary peritoneal, or fallopian tube cancers have received only 2 lines of platinum-based chemotherapies, and TNBC patients have received only 1 line of standard chemotherapy. Each prior chemotherapy must be given for at least 2 cycles.
At least one measurable lesion that can be accurately assessed by imaging (CT/MRI) at baseline
Subjects who have overall good overall general condition.
Signed informed consent.
Exclusion Criteria:
Subjects who received any previous treatment with any PARP inhibitors.
Subjects who received any previous treatment with any VEGFR inhibitors.
Less than 4 weeks from the last clinical trial.
Less than 4 weeks from the last radiotherapy, chemotherapy, surgery, hormone treatment and target therapy.
Unstable or uncontrolled hypertension.
Subjects that are unable to swallow, or dysfunction of gastrointestinal absorption.
Subjects with brain metastases.
Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry.
Subjects with a known hypersensitivity to fluzoparib, apatinib or any of the excipients of the products.
Ongoing infection (determined by investigator).
History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation.
Pregnant or breast-feeding women.
Facility Information:
Facility Name
Beijing Cancer Hosptial
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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A Study of Fluzoparib Given in Combination With Apatinib in Ovarian or Breast Cancer Patients
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