TAS-OX for Refractory Metastatic Colon Cancer

Inclusion Criteria

• Histologically confirmed stage IV colon cancer (AJCC 7th edition) that has progressed after standard therapy that included 5-FU, irinotecan and oxaliplatin. Patients who could not tolerate standard agents because of unacceptable, but reversible, toxicity necessitating their discontinuation will be allowed to participate.
• Patients who had received adjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant chemotherapy will be allowed to count the adjuvant therapy as one chemotherapy regimen.
• Progression of disease must be documented on the most recent scan.
• Presence of measurable disease (not required for Phase 1 portion of the trial).
• Retrovirus-associated DNA sequences (RAS) mutation and mismatch repair (MMR) status must be determined (or tissue availability for testing if not already determined)
• Age 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Life expectancy of at least 3 months.
• Patient with adequate organ function:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Hemoglobin ≥ 9 g/dL
• Platelets (PLT) ≥ 75 x 109/L
• Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 5 x Upper limit of normal (ULN)
• Total serum bilirubin of ≤1.5 mg/dL (except for Grade 1 hyperbilirubinemia due solely to a medical diagnosis of Gilbert's syndrome).
• Albumin ≥ 2.5 g/dL
• Serum creatinine ≤ 1.5 x institutional ULN (Cockcroft and Gault formula)
• Adequate contraception if applicable.
• Women who are nursing must discontinue nursing prior to enrollment in the program.
• Ability to take oral medication (i.e. no feeding tube).
• Patient able and willing to comply with study procedures as per protocol.
• Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures.

Exclusion Criteria

• Patients who have previously received TAS-102.
• Grade 2 or higher peripheral neuropathy.
• Symptomatic Central nervous system (CNS) metastases requiring treatment.
• Other active malignancy within the last 3 years (except for non-melanoma skin cancer or a non-invasive/in situ cancer).
• Pregnancy or breast feeding.
• Current therapy with other investigational agents.
• Active infection with body temperature ≥38°C due to infection.
• Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to drug administration).
• Any anticancer therapy within prior 3 weeks of first dose of study drug.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102.
• Current therapy with other investigational agents or participation in another clinical study or any investigational agent received within prior 4 weeks.
• Grade 3 or higher hypersensitivity reaction to oxaliplatin, or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with pre-medication.
• Unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum-induced neurotoxicity).
• Extended field radiation within prior 4 weeks of first dose of study drug or limited field radiation within prior 2 weeks of first dose of study drug.
• Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule.
• Involvement in the planning and/or conduct of the study.
• Previous enrollment in the present study.