A Phase Ib/II Study to Assess the Tolerability, Safety and Efficacy of Fluzoparib in Combination With mFOLFIRINOX Followed by Fluzoparib Maintenance Monotherapy in Patients With Advanced Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 2
- 主要终点
- Phase Ib：Recommended Phase 2 Dose
研究概览
简要总结
The study is being conducted to: a) evaluate the tolerability and safety of the co-administration of Fluzoparib and mFOLFIRINOX followed by Fluzoparib Maintenance Monotherapy in patients with advanced pancreatic cancer, and establish the maximum tolerated dose and recommended phase II dose of the combination; and b) assess the efficacy of the co-administration of Fluzoparib and mFOLFIRINOX followed by Fluzoparib Maintenance Monotherapy in patients with advanced pancreatic cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
- •Expected survival ≥ 6 months.
- •Histologically or cytologically confirmed local advanced/metastatic pancreas adenocarcinoma.
- •Documented mutation in germline BRCA1/2 or PALB2 that is predicted to be deleterious or suspected deleterious.
- •Adequate organ performance based on laboratory blood tests.
- •Presence of at least of one measurable lesion in agreement to RECIST criteria.
- •Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Patients who have received any chemotherapy for the treatment of pancreatic cancer prior to entering the study.
- •Previous treatment with any poly ADP-ribose polymerase (PARP) inhibitor.
- •Patients who have had radiotherapy or participated in another clinical trial with any investigational agents within 28 days of enrolment (Day 1 visit).
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin, irinotecan, 5-Fluorouracil or other agents used in the study.
- •Previous treatment using CYP3A4 inducers within 3 weeks or inhibitors within 2 weeks of enrolment (Day 1 visit).
- •Patients with known or suspected brain metastasis.
- •Significant cardiovascular disease such as New York Heart Associate Class III/IV, cardiac failure, myocardial infarction, unstable arrhythmia, or evidence of ischemia on ECG within 6 months prior to enrolment.
- •Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
- •Patients with myelodysplastic syndrome/acute myeloid leukaemia.
- •Patients with second primary cancer except curatively treated in-situ cancer or slowly progressing malignancy.
- •Known active hepatitis B or C infection.
- •History of immunodeficiency (including HIV infection) or organ transplantation.
- •Other serious accompanying illnesses, which, in the researcher's opinion, could seriously adversely affect the safety of the treatment.
研究组 & 干预措施
Fluzoparib+mFOLFIRINOX
Fluzoparib+mFOLFIRINOX followed by Fluzoparib maintenance monotherapy
干预措施: Fluzoparib (Drug)
Fluzoparib+mFOLFIRINOX
Fluzoparib+mFOLFIRINOX followed by Fluzoparib maintenance monotherapy
干预措施: mFOLFIRINOX (Drug)
Placebo+mFOLFIRINOX
Placebo+mFOLFIRINOX followed by placebo maintenance monotherapy
干预措施: Fluzoparib placebo (Drug)
Placebo+mFOLFIRINOX
Placebo+mFOLFIRINOX followed by placebo maintenance monotherapy
干预措施: mFOLFIRINOX (Drug)
结局指标
主要结局
Phase Ib：Recommended Phase 2 Dose
时间窗: Up to 2 years
Recommended Phase 2 Dose
Phase Ib：Number of Participants With a Dose Limited Toxicity
时间窗: Within 28 Days after The First Dose
Number of Participants With a Dose Limited Toxicity
Phase Ib：Maximum Tolerated Dose
时间窗: Up to 8 months
Maximum Tolerated Dose
Phase II：Objective Response Rate
时间窗: From Week 9 until documented disease progression or study discontinuation (approximately up to 24 months)
Objective response rate according to RECIST 1.1
次要结局
- Progression-Free-Survival(Up to 2 years)
- Time to maximum concentration (Tmax)(1 year)
- Duration of Response(Up to 2 years)
- Overall-Survival(Up to 2 years)
- Maximum concentration (Cmax)(1 year)
- Adverse events evaluated by NCI CTCAE v5.0(From the first drug administration to within 30 days for the last drug dose)
- Disease Control Rate(From Week 9 until documented disease progression or study discontinuation (approximately up to 24 months))
- Area under the curve (AUC)(1 year)