Adjuvant Chemotherapy in High Risk Stage II Colon Cancer

Study Overview
=================
Brief Summary
-----------------
Benefit of adjuvant chemotherapy after curative surgery for stage II Colon Cancer is still debated. Several high-risk features may help to stratify stage II cancer patients into groups that will truly benefit from adjuvant chemotherapy. However, those factors are rather subjective, and no specific trial has been designed to answer the high-risk stage II colon cancer question directly. Immunoscore® Colon, an in vitro diagnostic test, which quantifies the density of CD3+ and CD8+ T lymphocyte populations in the center the tumor (CT) and its invasive margin (IM) using immunohistochemistry and automated image analysis. Immunoscore® has been extensively validated as a prognostic biomarker in early stage CC patients. This unique diagnostic assay measuring host immune response at the tumor site may inform the decision to administer adjuvant chemotherapy in resected Stage II and III CC patients. This randomized trial is studying how observation compares to adjuvant chemotherapy (investigator's choice) in stage II colon cancer patients with high-risk features and High-Immunoscore®. The trial would represent a unique opportunity to classify stage II CC patients based on their tumor microenvironment with the aim to provide efficient patient stratification to improve clinical care.

Official Title
-----------------
Adjuvant Chemotherapy Versus Observation in Stage II Colon Cancer Patients With High-Risk Factors and High-Immunoscore®

Conditions
-----------------
Stage II Colon Cancer, Adjuvant Chemotherapy

Intervention / Treatment
-----------------
* Drug: FOLFOX/XELOX/Capecitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-75 years old Pathologically confirmed adenocarcinoma of the colon Complete resection of the primary tumor without gross or microscopic evidence of residual disease Histologically proven stage II: T3-T4 N0 At least one of the following factors:T4 staging,Number of examined lymph nodes < 12,poor differentiation (except MSI-H),LVI or PNI,tumor perforation or occlusion Treatment within 7 weeks following surgery ECOG PS 0-1 No prior chemo, immuno or radiotherapy Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study. Exclusion criteria Have a birth plan during the clinical trial; Severe cardiovascular diseases such as cerebrovascular accidents occurring within 6 months, myocardial infarction, hypertension that cannot be controlled after drug intervention, unstable angina pectoris, heart failure (NYHA 2-4), and arrhythmia requiring drugs Intervention; Dementia, mental state changes or any mental illness that may interfere with understanding or making informed consent or completing a questionnaire; Subjects with ≥1 peripheral neuropathy according to CTCAE V version 4.03; Allergy or hypersensitivity history of the drug or drug ingredient used in this test; Excluding other malignant tumors, cured basal cell carcinoma of the skin or squamous cell carcinoma of the skin or any other part of the carcinoma in situ; Have received any other test drug treatment or participated in another interventional clinical trial within 30 days of the screening period; The investigator believes that it is not suitable for inclusion.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: observation group<br>Patients enrolled in the observation group will not receive any chemotherapy drugs | |
| Experimental: adjuvant chemotherapy group<br>Patients enrolled in the chemotherapy group will receive postoperative chemotherapy (investigator's choice) for 3 months or 6 months. | Drug: FOLFOX/XELOX/Capecitabine<br>* Patients enrolled in the chemotherapy group will receive postoperative chemotherapy (investigator's choice) for 3 months or 6 months.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival (DFS) | To evaluate the noninferiority of observation as compared to standard of care adjuvant chemotherapy (investigator's choice) in patients with high-risk stage II CC and High-Immunoscore® in terms of disease free survival (DFS). | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Recurrence (TTR) | To evaluate the noninferiority of observation as compared to standard of care adjuvant chemotherapy (investigator's choice) in patients with high-risk stage II CC and High-Immunoscore® in terms of Time To Recurrence (TTR) | From date of enrollment until the date of recurrence,assessed 1year,3years and 5years after therapy | 
| Overall Survival (OS) | To evaluate the noninferiority of observation as compared to standard of care adjuvant chemotherapy (investigator's choice) in patients with high-risk stage II CC and High-Immunoscore® in terms of overall survival (OS) | From date of enrollment until the date of death,assessed 1year,3years and 5years after therapy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Stage II colon cancer, Adjuvant Chemotherapy, High-Risk factors, High-Immunoscore®