A Phase I Study of TAS-102 in Patients With Advanced Gastrointestinal Tumors.

A Phase 1, Open-label, Non-randomized, Dose-escalating Safety, Tolerability, and Pharmacokinetic Study of TAS-102 in Combination With CPT-11 and Bevacizumab in Patients With Advanced Gastrointestinal Tumors

The purpose of this study is to investigate the safety and determine the maximum tolerated dose of TAS-102 administered in combination with CPT-11 in patients with advanced gastrointestinal tumors.

This is an open-label, non-randomized, dose-escalation, Phase 1 study of TAS-102 administered in combination with CPT-11. The study will be conducted in 2 parts: a Dose Escalation Phase (Part 1) to determine the maximum tolerated dose and an Expansion Phase (Part 2) to further evaluate the safety, pharmacokinetics, and preliminary efficacy of the maximum tolerated dose. Patients will be assigned to sequential dose-level cohorts with each cohort corresponding to a pre-specified dose of TAS-102 and CPT-11 combination. Escalation to the subsequent dose level will occur only after the previous dose level is determined to be safe.

Inclusion Criteria:

1. Has provided written informed consent
2. Has advanced gastrointestinal tumors refractory to at least 1 chemotherapy
3. ECOG performance status of 0 or 1
4. Is able to take medications orally
5. Has adequate organ function (bone marrow, kidney and liver)
6. 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. Has had certain other recent treatment e.g. major surgery, extended field radiation, anticancer therapy, received investigational agent, within the specified time frames prior to study drug administration
2. Presence of serious illnesses or medical condition(s) e.g. brain metastases, systemic infection, heart failure
3. Has unresolved toxicity of greater than or equal to CTCAE Grade 1 attributed to any prior therapies
4. Known sensitivity to TAS-102, CPT-11, Bevacizumab, or their components
5. Is a pregnant or lactating female
6. Has had either partial or total gastrectomy