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

Study Overview
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Brief Summary
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The study is being conducted to: a) evaluate the tolerability and safety of the co-administration of Fluzoparib and FOLFIRINOX in patients with resectable pancreatic cancer, and establish a maximum tolerated dose and recommended phase II dose of the combination and b) assess the efficacy of the co-administration of Fluzoparib and FOLFIRINOX in patients with resectable pancreatic cancer.

Official Title
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A Phase I Study to Assess the Tolerability, Safety and Efficacy of Fluzoparib in Combination With mFOLFIRINOX as Neoadjuvant and Adjuvant Therapy in Patients With Resectable Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Fluzoparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-79 years. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 Expected survival ≥ 6 months. Histologically or cytologically confirmed pancreas adenocarcinoma. Resectable or borderline resectable pancreatic cancer. Adequate organ performance based on laboratory blood tests. Presence of at least of one measurable lesion in agreement to RECIST criteria. Ability to understand and the willingness to receive a needle biopsy. 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 had any chemotherapy or radiotherapy prior to entering the study. Patients with metastasis disease. Previous treatment with a poly ADP-ribose polymerase (PARP) inhibitor. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluzoparib+mFOLFIRINOX<br>Fluzoparib combined with FOLFIRINOX followed by maintenance Fluzoparib monotherapy | Drug: Fluzoparib<br>* Fluzoparib combined with mFOLFIRINOX followed by maintenance Fluzoparib monotherapy<br>* Other names: SHR3162;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with a dose limited toxicity | Number of participants with a dose limited toxicity | 28 Days (first and second cycle) | 
| Maximum tolerated dose | Maximum tolerated dose | Up to 8 months | 
| RP2D | Recommended Phase 2 Dose | Up to 8 months | 
| R0 resection rate | R0 resection rate of Fluzoparib in combination with FOLFIRINOX as neoadjuvant therapy in patients with resectable pancreatic cancer | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs | Incidence of adverse events and associated dose of Fluzoparib | From the first drug administration to within 30 days for the last drug dose | 
| Resection Rate | Resection rate of Fluzoparib in combination with FOLFIRINOX as neoadjuvant therapy in patients with resectable pancreatic cancer | Up to 2 years | 
| MPR Rate | Major pathological response rate based on central review | Up to 2 years | 
| Objective response rate | Objective response rate | Up to 2 years | 
| Disease-free-survival | Disease-free-survival | Up to 2 years | 
| Event-Free-Survival | Event-Free-Survival | Up to 2 years | 
| Overall-Survival | Overall-Survival | Up to 2 years | 
| Minimum concentration (Cmin) | Minimum observed plasma concentration for Fluzoparib | Up to 2 years |