Ph 2 Study of TAS-102 / Bevacizumab Maintenance Therapy Post Induction Chemotherapy in Metastatic Colorectal Cancer

Study Drug:

TAS-102 (trifluridine and tipiracil hydrocholoride) and bevacizumab

Dosing Details:

Starting dose of TAS-102 is 35 mg/m2 administered orally twice daily, after meals, for 5 days
a week with 2 days rest for 14 days, followed by 14 days rest (1 treatment cycle).

Bevacizumab 5 mg/kg intravenously every 14 days. The treatment cycle repeats every 28 days.
Patients may take TAS-102 plus bevacizumab until they exhibit progression of disease,
withdraw consent, or experience unacceptable toxicity.This is a single arm study. All
patients receive the same study treatment.

Inclusion criteria:

- Written informed consent

- Histologically proven, unresectable, evaluable metastatic colorectal cancer

- 16 to 20 weeks of first-line therapy with oxaliplatin, and/or irinotecan-based
flourorpyrimidine-containing chemotherapy plus Bevacizumab

- Patients must have stable disease (or better) during the initial induction
chemotherapy with first-line chemotherapy.

- No progressive disease at the time of initiation of maintenance therapy

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1

- Adequate organ and marrow function

- Women of child-bearing potential and men must agree to avoid pregnancy

- Patient must start maintenance therapy at least 14 days after the last administered
induction chemotherapy but no later than 30 days.

Exclusion Criteria

- Patients whose tumors have progressed on first-line treatment

- Patients with active concurrent malignancy, other than superficial, non-invasive
squamous cell carcinoma of the skin or uterine cervix, within the past three years.

- Women who are pregnant or lactating

- Unstable heart disease

- Uncontrolled active infection requiring antibiotics within one week prior to first
dose.

- Patients with active CNS malignancy.

- Persistent protein in the urine

- Patients with bowel obstruction or uncontrolled vomiting.

- Patients with serious psychiatric or medical conditions that could interfere with
treatment.