Randomized Double-Blind, Phase III Study of TAS-102 plus Best Supportive Care (BSC) Versus Placebo Plus Best Supportive Care in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapies
Trial Purpose and Description
This is multinational, double-blind, two-arm, parallel, randomized Phase 3 comparison study evaluating the efficacy and safety of TAS-102 vs. placebo in patientws with refractory metastatic colotrectal cancer. Patients will be randomly assigned (2:1) to TAS-102 (experimental arm) or placebo (control arm). Randomization will take place once the consented patient has completed all the necessary Baseline procedures and is deemed eligible for study entry. Treatment assignement will be done centrally using a dynamic allocation method (biased coin) via an Interactive Voice/Web Response System (IXRS) stratified by:
KRAS gene type (wild, mutant)
Time since diagnosis of first metastasis
Geographical region (Region 1:Asia/Japan, Region 2: Western/USA and Europe
- 18 Years and older
A patient must meet all of the following inclusion criteria to be eligible for enrollment in this study:
1. Has provided written informed consent prior to performance of any study procedure.
2. Is ≥18 years of age.
3. Has definitive histologically or cytologically confirmed adenocarcinoma of the colon or rectum.
a. KRAS status must have been determined (mutant or wild).
4. Has received at least 2 prior regimens of standard chemotherapies for metastatic colorectal cancer
and is refractory to or failing those chemotherapies.
a. Standard chemotherapy must include ALL of the following agents approved in each country:
i. Fluoropyrimidines, irinotecan and oxaliplatin
ii. An anti-VEGF monoclonal antibody (bevacizumab)
iii. At least one of the anti-EGFR monoclonal antibodies (cetuximab or panitumumab)
for KRAS wild-type patients.
b. Patients who have progressed based on imaging during or within 3 months of the last
administration of each standard chemotherapy.
c. Patients who have withdrawn from standard treatment due to unacceptable toxicity
warranting discontinuation of treatment and precluding retreatment with the same agent prior
to progression of disease will also be eligible to enter the study.
d. Patients who had received adjuvant chemotherapy and had recurrence during or within
6 months of completion of the adjuvant chemotherapy are allowed to count the adjuvant
therapy as one regimen of chemotherapy.
5. Has Eastern Cooperative Group (ECOG) performance status of 0 or 1 (see Appendix A) in the
Baseline period and on Cycle 1, Day 1.
6. Is able to take medications orally (ie, no feeding tube).
7. Has measurable or non-measurable metastatic lesion(s), as defined by RECIST version 1.1.
8. Has adequate organ function as defined by the following laboratory values obtained within 7 days
prior to study drug administration on Day 1 of Cycle 1:
a. Hemoglobin value of ≥9.0 g/dL.
b. Absolute neutrophil count of ≥1,500/mm3 (ie, ≥1.5 × 109/L by International Units [IU]).
c. Platelet count ≥100,000/mm3 (IU: ≥100 × 109/L).
d. Total serum bilirubin of ≤1.5 mg/dL (except for Grade 1 hyperbilirubinemia due solely to a
medical diagnosis of Gilbert’s syndrome).
e. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT)
≤3.0 × upper limit of normal (ULN); if liver function abnormalities are due to underlying
liver metastasis, AST and ALT ≤5 × ULN.
f. Serum creatinine of ≤1.5 mg/dL.
9. Women of childbearing potential must have a negative pregnancy test (urine or serum) within
7 days prior to randomization. Females must agree to adequate birth control if conception is
possible during the study and up to 6 months after the discontinuation of study medication; and
males must agree to adequate birth control during the study and up to 6 months after the
discontinuation of study medication.
10. Is willing and able to comply with scheduled visits and study procedures.
- Taiho Pharma USA, Inc.
- December 2012
- Last Updated:
- Study HIC#:
Clinicaltrials.gov ID: Yale7008739