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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- The type and incidence of adverse events [safety and tolerability]
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •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.
排除标准
- •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.
研究组 & 干预措施
Fluzoparib + Apatinib
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.
干预措施: Fluzoparib (Drug)
Fluzoparib + Apatinib
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.
干预措施: Apatinib (Drug)
结局指标
主要结局
The type and incidence of adverse events [safety and tolerability]
时间窗: From screening up to 28 days after end of treatment
Adverse events defined according to Common Terminology for Adverse Events (CTCAE) v4.03
次要结局
- CL/F(From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment)
- 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)
- Objective Response Rate (ORR)(24 months (approx) from the start of treatment)
- Cmax(From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment)
- Area under curve (AUC)(Within the first 5 weeks from start of fluzoparib treatment)
- V/F(From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment)
- Disease Control Rate (DOR)(24 months (approx) from the start of treatment)
- Overall Survival (OS)(From Cycle 1, Day 1 until death or up to 48 months (approx))
- T1/2 (Half-life)(From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment)