Ovarian Cancer, Triple Negative Breast Cancer
Conditions
Keywords
PARP inhibitor, VEGFR inhibitor, Combination therapy, Ovarian Cancer, Triple Negative Breast Cancer
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.
Interventions
DRUGFluzoparib
Fluzoparib either at 40,60,80mg twice daily,capsule oral.
DRUGApatinib
Apatinib at 250mg once daily, tablet oral
Sponsors
Peking University Cancer Hospital & Institute
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The type and incidence of adverse events [safety and tolerability] | From screening up to 28 days after end of treatment | Adverse events defined according to Common Terminology for Adverse Events (CTCAE) v4.03 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DOR) | 24 months (approx) from the start of treatment | \[Complete response + Partial response + Stable disease (CR+PR+SD)\] based on RECIST 1.1 |
| Time to Progression (TTP) | 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 | The time from start of the treatment until radiographic disease progression or CA-125 progression specific for ovarian cancer patients |
| Overall Survival (OS) | From Cycle 1, Day 1 until death or up to 48 months (approx) | Time from start of fluzoparib treatment until death due to any cause |
| Cmax | From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment | Maximum Plasma Concentration |
| Objective Response Rate (ORR) | 24 months (approx) from the start of treatment | \[Complete response + Partial response (CR+PR)\] based on RECIST 1.1 |
| Area under curve (AUC) | Within the first 5 weeks from start of fluzoparib treatment | Area under the plasma concentration-time curve |
| V/F | From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment | Volume of distribution |
| CL/F | From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment | Plasma Clearance |
| T1/2 (Half-life) | From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment | The time required for the plasma concentration of a drug to be reduced by 50% |
Countries
China
Outcome results
None listed