An Open Label, Single Arm, Multicenter Phase Ⅰb/Ⅱ Clinical Study of Fruquintinib Combined With Toripalimab and SOX Regimen in the First-line Treatment of Advanced Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Overview
- Phase
- Phase 1
- Intervention
- fruquintinib＋toripalimab + SOX
- Conditions
- Metastatic Gastric Cancer
- Sponsor
- The First Affiliated Hospital of Zhengzhou University
- Enrollment
- 64
- Locations
- 1
- Primary Endpoint
- RP2D
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a prospective, open-label, multicenter, single arm phase Ⅰb/Ⅱ clinical study aims to explore the efficacy and safety of fruquintinib combined with toripalimab and SOX regimen in the first-line treatment of unresectable advanced metastatic gastric or gastroesophageal junction adenocarcinoma.
Detailed Description
At present, the first-line standard treatment of metastatic gastric cancer is still doublet or triplet chemotherapy of fluorouracil combined with platinum or paclitaxel. In recent years, immune checkpoint inhibitors (ICIs) have emerged in advanced gastric cancer with their unique mechanism of action. PD-1 monoclonal antibody has been explored in multiple combination schemes in the first-line treatment of advanced gastric cancer. This study aims to explore the efficacy and safety of an antiangiogenetic TKI, fruquintinib combined with an ICI, toripalimab and the standard doublet SOX regimen in the first-line treatment of unresectable advanced metastatic gastric or gastroesophageal junction adenocarcinoma.
Investigators
Feng Wang
Professor
The First Affiliated Hospital of Zhengzhou University
Eligibility Criteria
Inclusion Criteria
- •Pathologically determined unresectable advanced gastric or gastroesophageal junction adenocarcinoma;
- •18-75 years old (including 18 and 75 years old);
- •No previous anti-tumor treatment for metastatic diseases;
- •HER2 negative;
- •Eastern Cooperation Oncology Group (ECOG) performance status of 0-1;
- •Life expectancy ≥ 3 months;
- •At least one measurable lesion according to RECIST version 1.1;
- •Adequate organ and bone marrow functions:
- •Absolute neutrophil count≥1.5x10\^9/L; Platelet count≥100x10\^9/L; Hemoglobin≥9g/dL; Serum bilirubin≤1.5x the upper limit of normal(ULN); Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)≤1.5x ULN; Serum creatinine≤1.5x ULN; Endogenous creatinine clearance rate ≥ 50ml / min;
- •Women of childbearing age need to take effective contraceptive measures.
Exclusion Criteria
- •Previous treatment with vascular endothelial growth factor receptor (VEGFR) inhibitors or previous use of immune checkpoint inhibitors;
- •Other malignant tumors in the past 5 years, except for skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ;
- •There was central nervous system (CNS) metastasis or previous brain metastasis before enrollment;
- •Patients with autoimmune diseases or history of autoimmune diseases within 4 weeks before enrollment;
- •Previously received allogeneic bone marrow transplantation or organ transplantation;
- •Uncontrolled malignant ascites;
- •Participated in other unapproved or unlisted drug clinical trials in China within 4 weeks before enrollment, and received corresponding experimental drug treatment;
- •Cardiovascular disease, including unstable angina or myocardial infarction, occurred within 6 months before the start of study treatment;
- •Subjects allergic to the study drug or any of its adjuvants;
- •International normalized ratio (INR) \> 1.5 or partially activated prothrombin time (APTT) \> 1.5 × ULN；
Arms & Interventions
Experimental
fruquintinib + toripalimab + SOX
Intervention: fruquintinib＋toripalimab + SOX
Outcomes
Primary Outcomes
RP2D
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
PFS
Time Frame: about 2 years
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first.
DLTs
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
DLTs are defined as grade 3 or higher adverse events that are related to fruquintinib during the first cycle of therapy.
Secondary Outcomes
- OS(about 2 years)
- DCR(about 2 years)
- DoR(about 2 years)
- adverse events (AEs) categorized by severity in accordance with the NCI CTC AE Version 5.0(about 2 years)
- ORR(about 2 years)