Efficacy of Postoperative Adjuvant Chemotherapy for Stage II Colon Cancer With High Risk Factors(EPAC1)

Study Overview
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Brief Summary
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The purpose of this study is to design a prospective randomized clinical trial to explore whether postoperative adjuvant chemotherapy may provide survival benefit for stage II colon cancer patients with high risk factors.Therefore the investigators can provide high level clinical evidence of indications for patients with colon cancer with stage II colon cancer.

Detailed Description
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The most controversial of adjuvant chemotherapy for colon cancer is whether stage II colon cancer should receive adjuvant chemotherapy or not. Because of the absolute little benefit of adjuvant chemotherapy after curative resection of stage II colon cancer，NCCN and ESMO guidelines do not recommend routine adjuvant chemotherapy for patients with stage II colon cancer unless combined with high risk factors. Currently，most studies about stage II colon cancer with high risk factors were retrospective. Some suggested that patients with stage II colon cancer can benefit from adjuvant chemotherapy, however, more got the negative conclusions. The study was designed as a multicenter, prospective, randomized, controlled trial.Patients who agreed to participate in the study would be randomly assigned to a treatment group of adjuvant chemotherapy or observation with 50% chance by a central randomization system determined by the computer program. After a follow up of at least 3 years, the disease free survival of the two groups will be compared.

Official Title
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Efficacy of Postoperative Adjuvant Chemotherapy for Stage II Colon Cancer With High Risk Factors(EPAC1)

Conditions
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Adjuvant Chemotherapy

Intervention / Treatment
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* Drug: CapeOX（Capecitabine+Oxaliplatin）
* Other: Observation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18 to 75 years; pathologically confirmed adenocarcinoma of the colon after curative resection pathological stage was T3-4N0M0; with at least one of the following factors: T4 staging lymph nodes number less than 12 poor differentiation (except MSI-H) LVI or PNI obstruction or perforation Elevated preoperative serum CEA ECOG Performance status 0-1 no evidence of distant metastases no preoperative chemotherapy or chemoradiation therapy ANC > 1.5 cells/mm3, HGB > 10.0 g/dL, PLT > 100,000/mm3, total bilirubin ≤ 1.5 xULN, AST≤ 3 x ULN, ALT ≤ 3 x ULN. Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study. Exclusion Criteria: combined with other cancer Creatinine level greater than 1.5 times the upper limit of normal. Patients who have received preoperative chemotherapy or chemoradiotherapy. Patients with a history of a prior malignancy within the past 5 years. Women who are pregnant or breast-feeding. patients may not complete the whole schedule of chemotherapy Patients with any other concurrent medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: a prospertive randomized clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: adjuvant chemotherapy group<br>patients enrolled int the adjuvant chemotherapy group will receive adjuvant chemotherapy[CapeOX（Capecitabine+Oxaliplatin）] by the current guidelines | Drug: CapeOX（Capecitabine+Oxaliplatin）<br>* Patients enrolled in the chemotherapy group would receive postoperative chemotherapy CapeOX（Capecitabine+Oxaliplatin）for 6 months<br>|
| Experimental: observation group<br>patients enrolled int the adjuvant chemotherapy group will not receive adjuvant chemotherapy just for observation | Other: Observation<br>* Patients enrolled in the observation group would not receive any chemotherapy drugs just for observation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year disease free survival | Disease free survival was defined as the duration after local recurrence or metastasis were found after surgery. Metastasis of any distant organs such as liver, lung, ovary，bone and peritoneum were defined by CT. | At least 3 years after the last patient enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year overall survival | Overall survival was defined as the duration from randomization to death from any cause | At least 3 years after the last patient enrolled | 
| Rate of metastasis | Rate of metastasis in different groups | At least 3 years after the last patient enrolled | 
| Relationship between high risk factors and survival | All the high risk factors enrolled in this study will be analyzed one by one to investigate the relationship between high risk factors and survival. | At least 3 years after the last patient enrolled | 
| Major adverse events | Toxic reaction in the chemotherapy group.Adverse events will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | At least 1 years after the last patient enrolled | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colon cancer, adjuvant chemotherapy, high risk