A Study of Fluzoparib Given in Combination With Apatinib and Paclitaxel in Gastric Cancer Patients

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Recurrent and Metastatic Gastric Cancer

Intervention / Treatment
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* Drug: Fluzoparib
* Drug: Apatinib
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluzoparib + Apatinib + Paclitaxel<br> | Drug: Fluzoparib<br>* Fluzoparib either at 20,30,40mg twice daily,capsule oral.<br>* Other names: SHR3162;Drug: Apatinib<br>* Oral<br>Drug: Paclitaxel<br>* Intravenous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | DLT and safety defined by CTC version 4.0 | through study completion, an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best of ORR |  | through study completion, an average of 6 months | 
| Overall Response Rate (ORR) |  | through study completion, an average of 6 months | 
| Disease Control Rate (DOR) |  | through study completion, an average of 6 months | 
| Time to Progression (TTP) |  | From date of enrollment until the date of first objective progression, assessed up to 9 months | 
| Progression Free Survival (PFS) |  | 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 | 
| Maximum plasma concentration (Cmax) |  | Up to 33 days | 
| Terminal half life (t1/2) |  | Up to 33 days | 
| Area under the plasma concentration-time curve (AUC） |  | Up to 33 days | 
| Volume of distribution (V/F) |  | Up to 33 days | 
| Plasma Clearance (CL/F) |  | Up to 33 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PARP inhibitor, VEGFR inhibitor, Combination therapy, Gastric cancer