Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies (RECOURSE)

• Progression-free survival [ Time Frame: 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. ] [ Designated as safety issue: No ]
• Safety and tolerability evaluation will focus on adverse events and laboratory assessments [ Time Frame: Through 30 days following last administration of study medication or until initiation of new anticancer treatment ] [ Designated as safety issue: Yes ]

• Progression-free survival [ Time Frame: Every 8 weeks. Tumor assessments will be performed until the patient develops radiologic progression or until the start of new anticancer treatment, for up to 12 months after the last patient is randomized. ] [ Designated as safety issue: No ]
• Safety and tolerability evaluation will focus on adverse events and laboratory assessments [ Time Frame: Through 30 days following last administration of study medication or until initiation of new anticancer treatment ] [ Designated as safety issue: Yes ]

The purpose of this study is to compare the efficacy and safety of TAS-102 versus placebo in patients with refractory metastatic colorectal cancer.

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).

• Drug: TAS-102
  35 mg/m2/dose, orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria are met.
• Drug: Placebo
  Placebo tablets, orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria are met.

• Experimental: TAS-102
  Intervention: Drug: TAS-102
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

1. Has provided written informed consent
2. Has adenocarcinoma of the colon or rectum
3. Has failed at least 2 prior regimens of standard chemotherapies for metastatic colorectal cancer
4. ECOG performance status of 0 or 1
5. Is able to take medications orally
6. Has adequate organ function (bone marrow, kidney and liver)
7. 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.

Exclusion Criteria:

1. Certain serious illnesses or medical condition(s)
2. Has had certain other recent treatment e.g. major surgery, anticancer therapy, extended field radiation, received investigational agent, within the specified time frames prior to study drug administration
3. Has received TAS-102
4. Has unresolved toxicity of greater than or equal to CTCAE Grade 2 attributed to any prior therapies
5. Is a pregnant or lactating female