Clinical trial NCT03026881: A Study of Fluzoparib Given in Combination With Apatinib and Paclitaxel in Gastric Cancer Patients
Official title: An Open, Non-randomised, Multi-centre Phase I Study to Assess the Safety and Efficacy of Fluzoparib Given in Combination With Apatinib and Paclitaxel in the 2nd Line Treatment of Patients With Recurrent or Metastatic Gastric Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Recurrent and Metastatic Gastric Cancer
Keywords: PARP inhibitor
VEGFR inhibitor
Combination therapy
Gastric cancer
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
First posted: 2017-01-20
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Fluzoparib is an oral potent, selective PARP-1 and PARP-2 inhibitor; Apatinib is an oral selective VEGFR inhibitor. This open-label, dose finding phase I trial studies the tolerability and the best dose of Fluzoparib in combination with apatinib and paclitaxel and to see how well this three drugs work together in the treatment of patients with recurrent and metastatic gastric cancer who progress following first-line therapy. The safety and efficacy of fluzoparib in combination with apatinib and paclitaxel will be explored.


Eligibility criteria: Inclusion Criteria:

* ECOG performance status of 0 to 1.
* Life expectancy of more than 12 weeks.
* Histologically or cytologically confirmed gastric adenocarcinoma( adenocarcinoma of the gastroesophageal junction included).
* Recurrent or metastatic gastric cancer that has progressed following first line-therapy.
* At least one lesion (measurable and/or non-measurable) that can be accurately assessed by imaging (CT/MRI) at baseline
* Subjects who have overall good overall general condition.
* Signed informed consent.

Exclusion Criteria:

* Subjects who received any previous treatment with any PARP inhibitors.
* Subjects who received any previous treatment with any taxanes.
* More than one prior chemotherapy regimen for the treatment of gastric cancer in the metastatic or recurrent setting.
* Less than 4 weeks from the last clinical trial.
* Less than 2 weeks from the last radiotherapy, chemotherapy, surgery, hormone treatment and target therapy.
* Unstable hypertension.
* Subjects that are unable to swallow, or dysfunction of gastrointestinal absorption.
* Subjects with brain metastases.
* Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry.
* Subjects with a known hypersensitivity to fluzoparib, apatinib, paclitaxel or any of the excipients of the product.
* Ongoing infection (determined by investigator).
* History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation.
* Subjects who can not interrupt the using of the drugs that may cause QT prolongation during study.
* Pregnant or breast-feeding women.

Primary outcomes:
measure: DLT and safety: Adverse Events (AEs), physical examination, vital signs including blood pressure (BP), pulse, electrocardiogram (ECG) and laboratory findings including clinical chemistry, hematology, urinalysis.
timeFrame: through study completion, an average of 6 months
Secondary outcomes:
measure: Best of ORR
timeFrame: through study completion, an average of 6 months
measure: Overall Response Rate (ORR)
timeFrame: through study completion, an average of 6 months
measure: Disease Control Rate (DOR)
timeFrame: through study completion, an average of 6 months
measure: Time to Progression (TTP)
timeFrame: From date of enrollment until the date of first objective progression, assessed up to 9 months
measure: Progression Free Survival (PFS)
timeFrame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, an average of 6 months
measure: Maximum plasma concentration (Cmax)
timeFrame: Up to 33 days
measure: Terminal half life (t1/2)
timeFrame: Up to 33 days
measure: Area under the plasma concentration-time curve (AUC）
timeFrame: Up to 33 days
measure: Volume of distribution (V/F)
timeFrame: Up to 33 days
measure: Plasma Clearance (CL/F)
timeFrame: Up to 33 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: The Affiliated Hospital of Military Medical Sciences
state: Beijing
Study officials:
References: