TAS-OX for Refractory Metastatic Colon Cancer

Inclusion Criteria:

1. 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.
2. 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.
3. Progression of disease must be documented on the most recent scan.
4. Presence of measurable disease (not required for Phase 1 portion of the trial).
5. Retrovirus-associated DNA sequences (RAS) mutation and mismatch repair (MMR) status must be determined (or tissue availability for testing if not already determined)
6. Age 18 years or older.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
8. Life expectancy of at least 3 months.
9. Patient with adequate organ function:

   1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
   2. Hemoglobin ≥ 9 g/dL
   3. Platelets (PLT) ≥ 75 x 109/L
   4. Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 5 x Upper limit of normal (ULN)
   5. Total serum bilirubin of ≤1.5 mg/dL (except for Grade 1 hyperbilirubinemia due solely to a medical diagnosis of Gilbert's syndrome).
   6. Albumin ≥ 2.5 g/dL
   7. Serum creatinine ≤ 1.5 x institutional ULN (Cockcroft and Gault formula)
10. Adequate contraception if applicable.
11. Women who are nursing must discontinue nursing prior to enrollment in the program.
12. Ability to take oral medication (i.e. no feeding tube).
13. Patient able and willing to comply with study procedures as per protocol.
14. 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:

1. Patients who have previously received TAS-102.
2. Grade 2 or higher peripheral neuropathy.
3. Symptomatic Central nervous system (CNS) metastases requiring treatment.
4. Other active malignancy within the last 3 years (except for non-melanoma skin cancer or a non-invasive/in situ cancer).
5. Pregnancy or breast feeding.
6. Current therapy with other investigational agents.
7. Active infection with body temperature ≥38°C due to infection.
8. Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to drug administration).
9. Any anticancer therapy within prior 3 weeks of first dose of study drug.
10. History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102.
11. Current therapy with other investigational agents or participation in another clinical study or any investigational agent received within prior 4 weeks.
12. Grade 3 or higher hypersensitivity reaction to oxaliplatin, or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with pre-medication.
13. 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).
14. 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.
15. Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule.
16. Involvement in the planning and/or conduct of the study.
17. Previous enrollment in the present study.