Clinical trial NCT01955837: Study of Trifluridine/Tipiracil (TAS-102) in Patients With Metastatic Colorectal Cancer in Asia
Official title: Randomized, Double-Blind, Phase III Study of TAS-102 Versus Placebo in Asian Patients With Metastatic Colorectal Cancer Refractory or Intolerable to Standard Chemotherapies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Lead sponsor: Taiho Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2013-10-08
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the effects of TAS-102 with placebo in patients with metastatic colorectal cancer refractory or intolerable to standard chemotherapies.

Detailed description: This is a multinational, double-blind, two-arm, parallel, randomized Phase 3 comparison study evaluating the efficacy and safety of TAS-102 versus placebo in patients with refractory metastatic colorectal cancer. Patients will be randomly assigned (2:1) to TAS-102 (experimental arm) or placebo (control arm).

Eligibility criteria: Inclusion Criteria:

* Has provided written informed consent
* Has adenocarcinoma of the colon or rectum
* Has failed at least 2 prior regimens of standard chemotherapies for metastatic colorectal cancer
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Is able to take medication orally
* Has adequate organ function (bone marrow, kidney and liver)
* Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control.

Primary outcomes:
measure: Overall Survival（OS）
timeFrame: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later.
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met.
measure: Time to Treatment Failure (TTF)
timeFrame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.
measure: Overall Response Rate (ORR; Complete Response [CR] or Partial Response [PR] Using RECIST Criteria)
timeFrame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.
measure: Disease Control Rate (DCR; CR, PR, or Stable Disease)
timeFrame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.
measure: Duration of Response
timeFrame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.
measure: Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events）
timeFrame: From the time a patient signed informed until 30 day safety follow-up visit or until initiation of new anticancer treatment, or assessed up to 30 months.
measure: Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments）
timeFrame: From the time a patient signed informed until 30 day safety follow-up visit or until initiation of new anticancer treatment, or assessed up to 30 months.
measure: Overall Survival（OS）(Wild Type KRAS)
timeFrame: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later.
measure: Overall Survival（OS）(Mutant Type KRAS)
timeFrame: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later.
measure: Progression-free Survival (PFS) (Wild Type KRAS)
timeFrame: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met.
measure: Progression-free Survival (PFS) (Mutant Type KRAS)
timeFrame: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Bangkok
country: Thailand
facility: Chulalongkorn University & The King Chulalongkorn Memorial Hospital
Study officials:
References:
citation: Xu J, Kim TW, Shen L, Sriuranpong V, Pan H, Xu R, Guo W, Han SW, Liu T, Park YS, Shi C, Bai Y, Bi F, Ahn JB, Qin S, Li Q, Wu C, Ma D, Lin D, Li J. Results of a Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of Trifluridine/Tipiracil (TAS-102) Monotherapy in Asian Patients With Previously Treated Metastatic Colorectal Cancer: The TERRA Study. J Clin Oncol. 2018 Feb 1;36(4):350-358. doi: 10.1200/JCO.2017.74.3245. Epub 2017 Dec 7.