Recurrent and Metastatic Gastric Cancer
Conditions
Keywords
PARP inhibitor, VEGFR inhibitor, Combination therapy, Gastric cancer
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.
Interventions
DRUGFluzoparib
Fluzoparib either at 20,30,40mg twice daily,capsule oral.
DRUGApatinib
Oral
DRUGPaclitaxel
Intravenous injection
Sponsors
The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | through study completion, an average of 6 months | DLT and safety defined by CTC version 4.0 |
Secondary
| Measure | 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 |
| 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 |
| Disease Control Rate (DOR) | through study completion, an average of 6 months |
| 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 |
| Maximum plasma concentration (Cmax) | Up to 33 days |
Countries
China
Contacts
Primary ContactJianming Xu, MD
Outcome results
None listed