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.

Study Overview

• Status: Unknown
• Conditions: Advanced Pancreatic Cancer
• Intervention / Treatment: Drug: Fluzoparib; Drug: mFOLFIRINOX; Drug: Fluzoparib placebo

• Study Type: Interventional
• Enrollment (Anticipated): 66
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Chunlei Jin, Ph.D; Phone Number: 86-021-23511999; Email: jinchunlei@hrglobe.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Xianjun Yu, M.D.
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Provincial People's Hospital
      • Contact: Yiping Mou, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluzoparib+mFOLFIRINOX; Fluzoparib+mFOLFIRINOX followed by Fluzoparib maintenance monotherapy	Drug: Fluzoparib; PARP; Other Names: SHR3162; Drug: mFOLFIRINOX; mFOLFIRINOX
Placebo Comparator: Placebo+mFOLFIRINOX; Placebo+mFOLFIRINOX followed by placebo maintenance monotherapy	Drug: mFOLFIRINOX; mFOLFIRINOX; Drug: Fluzoparib placebo; Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Xianjun Yu, M.D., Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2020
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 13, 2020
• First Posted (Actual): January 14, 2020

Study Record Updates

• Last Update Posted (Actual): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 9, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: SHR3162-Ib/II-112

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No