A Study of Fluzoparib in Combination With mFOLFIRINOX in Patients With Advanced Pancreatic Cancer
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Fluzoparib+mFOLFIRINOX Fluzoparib+mFOLFIRINOX followed by Fluzoparib maintenance monotherapy |
Drug: Fluzoparib
PARP
Other Names:
Drug: mFOLFIRINOX
mFOLFIRINOX
|
| Placebo Comparator: Placebo+mFOLFIRINOX Placebo+mFOLFIRINOX followed by placebo maintenance monotherapy |
Drug: Fluzoparib placebo
Placebo
Drug: mFOLFIRINOX
mFOLFIRINOX
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With a Dose Limited Toxicity [Within 28 Days after The First Dose]
Number of Participants With a Dose Limited Toxicity
- Maximum Tolerated Dose [Time Frame: Up to 8 months]
Maximum Tolerated Dose
- Objective Response Rate [From Week 9 until documented disease progression or study discontinuation (approximately up to 24 months)]
Objective response rate according to RECIST 1.1
Secondary Outcome Measures
- Adverse events evaluated by NCI CTCAE v5.0 [From the first drug administration to within 30 days for the last drug dose]
Incidence of adverse events and associated dose of Fluzoparib
- Disease Control Rate [From Week 9 until documented disease progression or study discontinuation (approximately up to 24 months)]
Disease control rate according to RECIST 1.1
- Duration of Response [Up to 2 years]
Duration of Response
- Progression-Free-Survival [Up to 2 years]
Time from randomisation until the date of objective radiological disease progression according to RECIST v1.1 or death
- Overall-Survival [Up to 2 years]
Time from the date of randomization until death due to any cause
- Area under the curve (AUC) [1 year]
Area under the plasma concentration time curve from 0 to 24 hours for Fluroparib
- Maximum concentration (Cmax) [1 year]
Maximum observed plasma concentration for Fluzoparib
- Time to maximum concentration (Tmax) [1 year]
Time to maximum plasma concentration for Fluzoparib
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Aged ≥ 18 years.
-
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
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Expected survival ≥ 6 months.
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Histologically or cytologically confirmed local advanced/metastatic pancreas adenocarcinoma.
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Documented mutation in germline BRCA1/2 or PALB2 that is predicted to be deleterious or suspected deleterious.
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Adequate organ performance based on laboratory blood tests.
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Presence of at least of one measurable lesion in agreement to RECIST criteria.
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Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
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Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
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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.
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Patients who have had radiotherapy or participated in another clinical trial with any investigational agents within 28 days of enrolment (Day 1 visit).
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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.
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Previous treatment using CYP3A4 inducers within 3 weeks or inhibitors within 2 weeks of enrolment (Day 1 visit).
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Patients with known or suspected brain metastasis.
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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.
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Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
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Patients with myelodysplastic syndrome/acute myeloid leukaemia.
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Patients with second primary cancer except curatively treated in-situ cancer or slowly progressing malignancy.
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Known active hepatitis B or C infection.
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History of immunodeficiency (including HIV infection) or organ transplantation.
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Other serious accompanying illnesses, which, in the researcher's opinion, could seriously adversely affect the safety of the treatment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fudan University Shanghai Cancer Center | Shanghai | Shanghai | China | |
| 2 | Zhejiang Provincial People's Hospital | Hangzhou | Zhejiang | China |
Sponsors and Collaborators
- Jiangsu HengRui Medicine Co., Ltd.
Investigators
- Principal Investigator: Xianjun Yu, M.D., Fudan University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SHR3162-Ib/II-112