A Study of Fluzoparib in Combination With mFOLFIRINOX in Patients With Advanced 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 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.

Official Title
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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

Conditions
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Advanced Pancreatic Cancer

Intervention / Treatment
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* Drug: Fluzoparib
* Drug: Fluzoparib placebo
* Drug: mFOLFIRINOX


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluzoparib+mFOLFIRINOX<br>Fluzoparib+mFOLFIRINOX followed by Fluzoparib maintenance monotherapy | Drug: Fluzoparib<br>* PARP<br>* Other names: SHR3162;Drug: mFOLFIRINOX<br>* mFOLFIRINOX<br>|
| Placebo Comparator: Placebo+mFOLFIRINOX<br>Placebo+mFOLFIRINOX followed by placebo maintenance monotherapy | Drug: Fluzoparib placebo<br>* Placebo<br>Drug: mFOLFIRINOX<br>* mFOLFIRINOX<br>|

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 | Within 28 Days after The First Dose | 
| Maximum Tolerated Dose | Maximum Tolerated Dose | Time Frame: Up to 8 months | 
| Objective Response Rate | Objective response rate according to RECIST 1.1 | From Week 9 until documented disease progression or study discontinuation (approximately up to 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events evaluated by NCI CTCAE v5.0 | Incidence of adverse events and associated dose of Fluzoparib | From the first drug administration to within 30 days for the last drug dose | 
| Disease Control Rate | Disease control rate according to RECIST 1.1 | From Week 9 until documented disease progression or study discontinuation (approximately up to 24 months) | 
| Duration of Response | Duration of Response | Up to 2 years | 
| Progression-Free-Survival | Time from randomisation until the date of objective radiological disease progression according to RECIST v1.1 or death | Up to 2 years | 
| Overall-Survival | Time from the date of randomization until death due to any cause | Up to 2 years | 
| Area under the curve (AUC) | Area under the plasma concentration time curve from 0 to 24 hours for Fluroparib | 1 year | 
| Maximum concentration (Cmax) | Maximum observed plasma concentration for Fluzoparib | 1 year | 
| Time to maximum concentration (Tmax) | Time to maximum plasma concentration for Fluzoparib | 1 year |