Maintenance Tegafur-uracil in Resected Oral Cavity Cancer With ECS+

A Phase II Study of Maintenance Tegafur-uracil in Patients With Squamous Cell Carcinoma of Oral Cavity With Extracapsular Spreading of Lymph Nodes

Primary Objective:

To determine the 2-year distant failure rate of maintenance tegafur-uracil in patients with squamous cell carcinoma of oral cavity with extracapsular spreading of lymph nodes.

Secondary Objectives:

• To determine the 2-year locoregional failure rate.
• To evaluate the 2-year overall survival (OS) rate.
• To evaluate the 2-year progression-free survival (PFS) rate.
• To assess the safety profiles.

The primary endpoint will be 2-years distant failure rate which will be estimated by Kaplan-Meier method with two-sided 95% confidence interval.

The secondary endpoints are described as follows:

• 2-year locoregional failure rate, 2-year PFS rate and 2-year OS rate will be estimated by Kaplan-Meier method with two-sided 95% confidence interval.
• Safety profile: adverse events will be summarized by CTCAE. Safety parameters will only be analyzed on the safety analysis set and be presented in frequency tabulation.

Determination of sample size:

The estimated 2-year distant failure rate for squamous cell carcinoma of oral cavity with extracapsular spreading of lymph nodes is 26%. The 2-year distant failure rate of maintenance treatment with tegafur-uracil in this study is expected to be 13%. Using One Proportional Test with one-sided alpha 0.05 and power 80%, the sample size of 56 subjects will test an effect size of 13% (i.e. 26% vs.13%). With expected dropout rate of 20%, the sample size would be 68 subjects.

Inclusion Criteria:

• Patient must have histologically confirmed squamous cell carcinoma with primary site in the oral cavity.

• Patient must have no distant metastasis in the pre-adjuvant radiotherapy evaluation.

• Patient must have received surgical treatment with pathologically documented extracapsular spreading of lymph node.

• Patient must have no CTCAE 4.0 grading≧2 acute adverse events from previous definite treatment at enrollment.

• Patient must can be enrolled within 1 to 3 months after definite treatment.

• Age between 20 and 70 years old;

• Patient must have ECOG performance status score 0 or 1;

• Patient must have adequate hematopoietic function which is defined as below:

  1. white blood cell (WBC) ≥ 4,000/mm3;
  2. platelet count ≥ 100,000/mm3;
  3. absolute neutrophil count (ANC) ≥ 1,500/mm3;

• Patients must have adequate hepatic function which is defined as below:

  1. serum bilirubin level < 1.5 mg/dl;
  2. sGOT and sGPT < 2.5 x ULN;
  3. serum creatinine level < 1.5 x ULN;

• All women of childbearing potential must have a negative serum or urine pregnancy test prior to the start of study medication;

• Patient with childbearing potential must agree to use a reliable contraceptive method during their participation in the study;

• Patient must have the ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Patient who has distant metastasis;
• Patient who has serious concomitant illness which might be aggravated by chemotherapy;
• Other malignancy within 5 years prior to study entry with exception of curative treated basal or squamous cell skin cancer or cervical carcinoma in situ.
• Female patient who is pregnant or breast feeding.