A Study of Fluzoparib Given in Combination With Apatinib in Ovarian or Breast Cancer Patients

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Ovarian Cancer, Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: Fluzoparib
* Drug: Apatinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluzoparib + Apatinib<br>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. | Drug: Fluzoparib<br>* Fluzoparib either at 40,60,80mg twice daily,capsule oral.<br>* Other names: HS10160;Drug: Apatinib<br>* Apatinib at 250mg once daily, tablet oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The type and incidence of adverse events [safety and tolerability] | Adverse events defined according to Common Terminology for Adverse Events (CTCAE) v4.03 | From screening up to 28 days after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | [Complete response + Partial response (CR+PR)] based on RECIST 1.1 | 24 months (approx) from the start of treatment | 
| Disease Control Rate (DOR) | [Complete response + Partial response + Stable disease (CR+PR+SD)] based on RECIST 1.1 | 24 months (approx) from the start of treatment | 
| Time to Progression (TTP) | The time from start of the treatment until radiographic disease progression or CA-125 progression specific for ovarian cancer patients | 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 | 
| Overall Survival (OS) | Time from start of fluzoparib treatment until death due to any cause | From Cycle 1, Day 1 until death or up to 48 months (approx) | 
| Cmax | Maximum Plasma Concentration | From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment | 
| T1/2 (Half-life) | The time required for the plasma concentration of a drug to be reduced by 50% | From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment | 
| Area under curve (AUC) | Area under the plasma concentration-time curve | Within the first 5 weeks from start of fluzoparib treatment | 
| V/F | Volume of distribution | From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment | 
| CL/F | Plasma Clearance | From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PARP inhibitor, VEGFR inhibitor, Combination therapy, Ovarian Cancer, Triple Negative Breast Cancer