Clinical trial NCT04228601: A Study of Fluzoparib in Combination With mFOLFIRINOX in Patients With Advanced Pancreatic Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Pancreatic Cancer
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-01-14
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase Ib：Number of Participants With a Dose Limited Toxicity
timeFrame: Within 28 Days after The First Dose
measure: Phase Ib：Maximum Tolerated Dose
timeFrame: Up to 8 months
measure: Phase Ib：Recommended Phase 2 Dose
timeFrame: Up to 2 years
measure: Phase II：Objective Response Rate
timeFrame: From Week 9 until documented disease progression or study discontinuation (approximately up to 24 months)
Secondary outcomes:
measure: Adverse events evaluated by NCI CTCAE v5.0
timeFrame: From the first drug administration to within 30 days for the last drug dose
measure: Disease Control Rate
timeFrame: From Week 9 until documented disease progression or study discontinuation (approximately up to 24 months)
measure: Duration of Response
timeFrame: Up to 2 years
measure: Progression-Free-Survival
timeFrame: Up to 2 years
measure: Overall-Survival
timeFrame: Up to 2 years
measure: Area under the curve (AUC)
timeFrame: 1 year
measure: Maximum concentration (Cmax)
timeFrame: 1 year
measure: Time to maximum concentration (Tmax)
timeFrame: 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
Study officials:
affiliation: Fudan University
name: Xianjun Yu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: