A Study of Fluzoparib in Combination With mFOLFIRINOX in Patients With Advanced Pancreatic Cancer

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

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.