Adjuvant Chemotherapy in Clinical Local Advanced CRC Following Preoperational Therapies and pT0-3N0M0 Diagnosis

Study Overview
=================
Brief Summary
-----------------
Adjuvant chemotherapy was unnecessary in pathological stage Ⅱ colorectal cancer following initial treatment of surgery without high risk factors of recurrences. The treatment efficacy of adjuvant chemotherapy for pT1-3N0M0 colorectal cancer following preoperational chemotherapy or chemoradiotherapy remains unclear. Part of clinical local advanced colorectal cancer(cTxN1-2M0), which turn out to be pT0-3N0M0 after preoperational chemotherapy or chemoradiotherapy, might not really need adjuvant chemotherapy due to the down-stage efficacy of the preoperational treatments, or the misleading by lymph nodes false-positive imaging diagnosis.

Detailed Description
-----------------
Colorectal cancer(CRC) nowadays rank the 3rd incidence and the 4th mortality in all cancers worldwide(ref). Although the coloscopy or liquid biopsy screen has improved the early diagnosis of CRC, about 26.5-36.0% of the patients were diagnosed local advanced CRC at the first visit. Part of clinical local advanced colorectal cancer(cTxN1-2M0), which turn out to be pT1-3N0M0 after preoperational chemotherapy or chemoradiotherapy, might not really need adjuvant chemotherapy due to the down-stage efficacy of the preoperational treatments, or the misleading by lymph nodes false-positive imaging diagnosis. Adjuvant chemotherapy was been admitted unnecessary in the pathological stage ⅡA (pT0-3N0M0) CRC following initial treatment of surgery without high risk factors of recurrences. The treatment efficacy of adjuvant chemotherapy for pT1-3N0M0 CRC following preoperational chemotherapy or chemoradiotherapy remains unclear. The aim of this study is to evaluate the efficacy/safety of adjuvant chemotherapy in clinical local advanced CRC (cTxN1/2M0) following preoperational adjuvant therapies and pathologically proved pT0-3N0M0 CRC. Patients are randomized to control group(down-staged pT0-3N0M0 CRC with 6 to 8 periods adjuvant chemotherapy) and experimental group(watch group, down-staged pT0-3N0M0 CRC without adjuvant chemotherapy). The primary endpoint is the 3-years disease-free survival after surgery. Secondary endpoints evaluate long-term clinical outcomes, in particular overall survival and side effect of chemotherapy.

Official Title
-----------------
Comparing the Treatment Efficacy in Clinical Local Advanced Colorectal Cancer (cTxN1/2M0) Following Preoperational Adjuvant Therapies and Pathologically Proved StageⅡ(pT0-3N0M0)With or Without Adjuvant Chemotherapy

Conditions
-----------------
Colorectal Cancer, Adjuvant Chemotherapy

Intervention / Treatment
-----------------
* Behavioral: wait and watch
* Drug: adjuvant chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: preoperative clinical tumor stage III （TxN1-2M0）CRC pathological proved CRC adenocarcinoma by endoscopic biopsy Post operational pathological T0-3N0M0 without high risk factors of recurrence Patient able to understand and sign written informed consent Exclusion Criteria: Other malignant tumors history. Complications need emergency surgery (occlusion, sub-occlusion, massive hemorrhage and abscesses). Colorectal tumor extension towards abdominal wall and/or adjacent organ making liver R0 resection impossible immediately. Non resectable lymph node metastasis. American Society of Anesthesiologists (ASA) grading≥ IV and/or, Eastern Cooperative Oncology Group(ECOG) score≥ 2. Physical or psychological dependence. Pregnant or breast feeding women. Not controlled pre-operational infection. Enrolled in other clinical trials within 4 weeks. Other clinical or laboratorial condition not recommended by investigators.

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 |
| --- | --- |
| Experimental: wait and watch group<br>clinical local advanced colorectal cancer (cTxN1/2M0) following pre-operational adjuvant therapies and pathologically proved stageⅡ(pT0-3N0M0) without adjuvant chemotherapy | Behavioral: wait and watch<br>* clinical local advanced colorectal cancer (cTxN1/2M0) following preoperational adjuvant therapies and pathologically proved stageⅡ(pT0-3N0M0),without(wait and watch) adjuvant chemotherapy<br>|
| Active Comparator: adjuvant chemotherapy group<br>clinical local advanced colorectal cancer (cTxN1/2M0) following preoperational adjuvant therapies and pathologically proved stageⅡ(pT0-3N0M0) with adjuvant chemotherapy | Drug: adjuvant chemotherapy<br>* clinical local advanced colorectal cancer (cTxN1/2M0) following preoperational adjuvant therapies and pathologically proved stageⅡ(pT0-3N0M0),with adjuvant chemotherapy<br>* Other names: mFOLFOX6;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease free survival | 3years disease-free survival rate | 3years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | 5years overall survival rate | 5years | 
| adverse reaction of adjuvant therapies | Rate of participants with myelosuppression, gastrointestinal reaction, infection, lose hair | 3years | 
| remission rate of adjuvant therapies | CRC remission evaluation using RECIST after adjuvant therapies | 1year | 
| death rate within 30 days post surgery | death related directly with operation within 30 days | 30days | 
| complication in 30 days post surgery | Rate of participants with complications such as bleeding，infection，anastomotic fistula,etc | 30days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
local advanced colorectal cancer, adjuvant chemotherapy