A Phase Ib/2 Clinical Study of Fruquintinib Combined With Paclitaxel in the Treatment of Advanced Gastric Cancer

Overview

An open-label, dose escalation and maximum tolerated dose (MTD) and/or recommended phase II dose (RPTD) study of fruquintinib combined with paclitaxel in patients with advanced gastric cancer who did not respond to first-line standard chemotherapy.

In dose escalation period, 12-24 patients with advanced gastric cancer will be enrolled. Patients meeting enrollment eligibility will receive 28-day cycles of fruquintinib 2-5 mg qd combined with paclitaxel 80 mg/m2. Safety information and pharmacokinetic data will be collected till disease progression or intolerable toxicity to determine MTD and/or RPTD of fruquintinib combined with paclitaxel in patients with advanced gastric cancer. This period will include the following 4 dose groups from low to high: A: Fruquintinib 2 mg qd for 3 weeks followed by 1-week break + paclitaxel 80 mg/m2 once a week during the first three weeks of each cycle B: Fruquintinib 3 mg qd for 3 weeks followed by 1-week break + paclitaxel 80 mg/m2 once a week during the first three weeks of each cycle C: Fruquintinib 4 mg qd for 3 weeks followed by 1-week break + paclitaxel 80 mg/m2 once a week during the first three weeks of each cycle D: Fruquintinib 5 mg qd for 3 weeks followed by 1-week break + paclitaxel 80mg/m2 once a week during the first three weeks of each cycle This study will use traditional 3+3 trial design (3 subjects will be enrolled in each dose group first. If 1 case of DLT is observed, additional 3 subjects will be enrolled in the same dose group to further evaluate toxicity) to observe DLT and evaluate MTD. If there are 2 or more cases of DLT in one dose group, the group lower than this dose group by one level is MTD dose group. At least 6 subjects are required in MTD dose group for confirmation. If MTD is not achieved at the end of dose escalation and there are 6 subjects in the highest dose group, RPTD can be determined based on obtained safety, tolerability, PK and efficacy information. Dose escalation and study in the next dose group can be initiated only after the first treatment cycle (DLT window observation period) is completed and subject safety and tolerability are confirmed in this dose group (0/3 or ≤1/6 subjects experience DLT). Subjects in the original dose group will continue to receive the next cycle of treatment at the original dose till disease progression or treatment withdrawal due to any of the following reasons: 1) death, 2) intolerable toxicity, 3) pregnancy, 4) the investigator considers the study should be terminated for the subject's best interests, 5) the subject or legal representative requests withdrawal, 6) loss to follow-up, 7) the subject has poor compliance and cannot comply with the study protocol.

Conditions

Interventions

Eligibility

Locations (3)

Outcomes