Maintenance Tegafur-uracil Versus Observation Following Adjuvant Oxaliplatin-based Regimen in Patients With Stage III Colon Cancer After Radical Resection

Primary Objective:

To compare 3-year disease free survival (DFS) of tegafur-uracil following adjuvant oxaliplatin-based regimen to observation following adjuvant oxaliplatin-based regimen in patients with stage III colon cancer after radical resection.

Secondary Objectives:

• To assess 5-year overall survival (OS) in each arm
• To assess the safety profiles

Objectives:

1. Primary Objective:

   To compare 3-year disease free survival (DFS) of tegafur-uracil following adjuvant oxaliplatin-based regimen to observation following adjuvant oxaliplatin-based regimen in patients with stage III colon cancer after radical resection.

2. Secondary Objectives:

   • To assess 5-year overall survival (OS) in each arm
   • To assess the safety profiles

Patient Selection and Enrollment:

Number of Subjects: Eligible patients will be randomized in 2 arms in the ratio of 2:1, to reach approximately 546 patients in total.

Plan of the Study:

1. Study Design This is an open-label, randomized, comparative, double arm, multicenter study to assess disease free survival, overall survival, safety profiles with tegafur-uracil following adjuvant oxaliplatin-based regimen as maintenance for one-year in patients with stage III colon cancer after radical resection in Taiwan.
2. Subject Number Eligible patients will be randomized in 2 arms in the ratio of 2:1, to reach approximately 546 patients in total.
3. Study Schedule Study date: the time getting approval letter issued by both regulatory authority and institutional review board (IRB) Expected recruitment rate: 23 subjects/month Duration of recruitment: at least 2 years. Duration of the study: at least 5 years.
4. Visit Schedule The schedule of assessments (please refer section 8.4 for the details) indicates the number and timing of the planned visits, which must be maintained as accurately as possible. The visit schedule must be maintained as accurate as possible.
5. Duration of Treatment Treatment should be administered up to maximum one year, disease progression, intolerable toxicity, or consent withdrawal during any time of the study, the patient will be withdraw.

Inclusion Criteria:

To be eligible for inclusion, each subject must fulfill all of the following criteria:

1. pathologically confirmed colon carcinoma;
2. stage III disease (T1-4, N1-2, M0 as defined by AJCC 7th Edi.);
3. completion of adjuvant oxaliplatin-based regimen without evidence of any recurrent disease;
4. entry of the trial within 3 weeks after adjuvant oxaliplatin-based regimen;
5. performance status of ECOG 0, 1, 2;
6. age between 20 and 80 years old;
7. written informed consent to participate in the trial.

Exclusion Criteria:

Patients who fulfill any of the following criteria will be excluded from the trial:

1. previous or current systemic malignancy with the exception of curatively treated non-melanoma skin cancer or cervical carcinoma in situ, unless there has been a disease-free interval of at least 5 years;

2. inadequate hematopoietic function defined as below:

   1. hemoglobin < 9 g/dL;
   2. absolute neutrophil count (ANC) < 1,500/mm3;
   3. platelet count < 100,000/mm3;

3. inadequate organ functions defined as below:

   1. total bilirubin > 2 times upper limit of normal (ULN);
   2. hepatic transaminases (ALT and AST) > 2.5 x ULN;
   3. creatinine > 1.5 x ULN;

4. other significant medical conditions that are contraindicated to tegafur-uracil or render patient at high risk from treatment complications based on investigator's discretion;

5. presence of other serious concomitant illness;

6. participation in another clinical trial with any investigational drug within 30 days prior to entry;

7. pregnant or lactating women or women of childbearing potential.