Study of Afuresertib Combined With Paclitaxel in Gastric Cancer
Status:
Completed
Trial end date:
2017-02-07
Target enrollment:
Participant gender:
Summary
This is a Phase Ib, open-label, dose-escalation study to determine the Maximal tolerated dose
(MTD) and the recommended Phase 2 dose (RP2D) for the combination of afuresertib and
paclitaxel in subjects with recurrent HER2-negative gastric cancer, and further assess safety
and preliminary efficacy of combination at the RP2D. Afuresertib had showed synergistic
activity when combined with paclitaxel in vitro and in vivo models of gastric cancer. Dose
escalation will continue until the MTD is established. The dose schedule is once daily (QD)
dosing for afuresertib and intravenous (IV) infusion for paclitaxel Dose escalation in Part 1
will follow the 3 + 3 cohort design. A sequential approach will be conducted to explore the
optimal paclitaxel regimen (weekly or 3weekly schedule) when combined with afuresertib. The
dose escalation will be started from Cohort A (afuresertib combined with weekly paclitaxel
regimen at 80 milligram (mg)/meter (m)^2 day1, 8,15, every 4 weeks (q4w). The starting dose
in Cohort A will be 125 mg afuresertib QD. Once its MTD is identified, and then the study
will move to dosing Cohort B (afuresertib combined with 3 weekly paclitaxel regimen at 175
mg/m^2 day1, every 3 week (q3w). The starting daily dose of Cohort B will be 25 mg less than
the MTD dose from Cohort A for afuresertib. If it is tolerated, then the dose escalation
schedule will be followed in Cohort B until the MTD in this Cohort is reached. If the
starting dose is not tolerated, then dose de-escalation will be explored until the MTD in
this Cohort is reached. Once two dimensions of the MTD are achieved, then the optimal regimen
for paclitaxel and MTD for afuresertib combined with paclitaxel based on the toxicity profile
will be identified. The combination regimen at the RP2D selected following Part I will be
further investigated in its efficacy and safety in the Part II Expansion Cohort. Once a
combination dose regimen for Part 2 has been determined, at least 20 and up to 40 subjects
will be enrolled at the dose regimen selected following Part I. Overall response rate (ORR)
will be evaluated using a Green-Dahlberg design. The design consists with one interim
analysis. If less than 3 responses are observed in the initial 20 subjects, enrollment will
be terminated due to futility; otherwise, the study will continue to meet the planned sample
size of 40 subjects.