This is an open-label, Phase 1b study which will be conducted in two parts: part A is the dose escalation study while part B is dose expansion study. The purpose of the dose escalation part is to identify the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of CM082 combined with paclitaxel in patients with advanced gastric cancer who did not respond to first-line standard chemotherapy. In the subsequent dose expansion part, additional subjects will be enrolled to further explore the safety and preliminary clinical activity of CM082 and paclitaxel.
In dose escalation part, 9-18 patients with advanced gastric cancer will be enrolled. Patients meeting enrollment eligibility will receive 28-day cycles of CM082 100-200 mg qd combined with paclitaxel 80 mg/m2. Safety information will be collected in cycle 1 to determine MTD and/or RP2D of CM082 combined with paclitaxel in patients with advanced gastric cancer. Dose escalation study will use traditional 3+3 trial design 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, 200 mg qd will be determined as RP2D. 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 safety and tolerability in subject is 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 until it meets the following discontinued treatment criteria: 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 investigator considers the subject has poor compliance, 8) disease progression, 9) the investigator considers the toxicity effect will be intensified if the study continues, 10) use other anti-tumor drugs. In dose-expansion part, additional patients will be treated at the RP2D established in dose escalation part until it meets the discontinued treatment criteria.
Study Type
INTERVENTIONAL
Allocation
NA
CM082 treatment: A treatment cycle is defined as 28 days. Oral CM082 tablets was given once daily for 3 weeks followed by 1-week break with escalating dose (100 mg, 150 mg and 200mg). Drug: Paclitaxel Paclitaxel 80 mg/m2 will be administrated by intravenous injection on days 1, 8, 15 of a 28-day cycle for no more than 6 cycles.
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Beijing, China
RECRUITINGDLT and MTD
DLTs were defined as grade 4 hematological toxicity; grade 3 or more severe nonhematologic toxicity including nausea/vomit, constipation , Hypertension , not controlled by adequate supportive treatment (with exceptions of alopecia); grade 3 febrile neutropenia. The MTD was defined as the highest dose at which no DLT was experienced by the first 3 patients in that cohort, or the dose at which a DLT was experienced by no more than 1 of 6 patients evaluable for toxicity.
Time frame: 4 weeks
Percentage of patients who suffer at least one adverse event
Adverse event assessment and changes in safety assessments include laboratory parameters, vital signs, and ECOG score
Time frame: From first dose to within 28 days after the last dose
Objective response rate
Defined as the rate of either a complete response or a partial response in evaluable patients
Time frame: 12 weeks
Progression-free survival
Defined as the time from randomisation to disease progression or death
Time frame: 6 months
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Purpose
TREATMENT
Masking
NONE
Enrollment
21