Clinical trial NCT03075462: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Triple Negative Breast Cancer
Keywords: PARP inhibitor
VEGFR inhibitor
Combination therapy
Ovarian Cancer
Triple Negative Breast Cancer
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Peking University Cancer Hospital & Institute
First posted: 2017-03-09
Enrollment: 98
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: The type and incidence of adverse events [safety and tolerability]
timeFrame: From screening up to 28 days after end of treatment
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 24 months (approx) from the start of treatment
measure: Disease Control Rate (DOR)
timeFrame: 24 months (approx) from the start of treatment
measure: Time to Progression (TTP)
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: From Cycle 1, Day 1 until death or up to 48 months (approx)
measure: Cmax
timeFrame: From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment
measure: T1/2 (Half-life)
timeFrame: From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment
measure: Area under curve (AUC)
timeFrame: Within the first 5 weeks from start of fluzoparib treatment
measure: V/F
timeFrame: From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment
measure: CL/F
timeFrame: From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hosptial
state: Beijing
Study officials:
References: