Resection vs no Resection of the Primary in Colorectal Cancer With Unresectable Metastases

Study Overview
=================
Brief Summary
-----------------
Main outcome: Assess the impact of cancer-related survival at 2 years in patients with unresectable metastatic colorectal cancer treated with chemotherapy alone versus surgery followed by chemotherapy. To assess overall survival. To evaluate postoperative morbidity and mortality in patients treated with resection of the primary tumor. Assess complications and meed for surgery in patients treated with systemic chemotherapy only during the course of the disease. Identify and describe the complications related to chemotherapy and toxicity in the short and medium term systemic treatment. Assessing the quality of life questionnaire QLQ-C30 and QLQ-CR29. To study prognostic survival factors. Method: multicenter randomized clinical trail (22 hospitals). Two parallel group in which to evaluate two therapeutic strategies for colorectal cancer metastasis unresectable stage IV: chemotherapy alone versus primary tumor resection plus chemotherapy. Subjects: patients with unresectable nonmetastatic colorectal cancer. Hypothesis:Surgical resection of the primary tumor in stage IV colorectal patients with unresectable synchronous metastases increases by 14% overall survival compared to patients receiving systemic treatment with chemotherapy without resection of the primary tumor (survival of 34% vs 20%).

Detailed Description
-----------------
Intervention: Arm B (control): chemotherapy alone, regimen according to each center. Arm A (experimental): surgery (complete tumoral resection; R0) followed by chemotherapy, regimen according to each center. Statistical Analysis: A power analysis showed that to assure a significance level of 0,05 and a beta error 0.20. 168 patients are necessary in each arm. It has been estimated a loss rate of up to 10%. Differences between groups will be analyzed by t, U, X2, exact test and survival will be assessed according to Kaplan and Meier method. Evaluation of safety of the trial will be made in the middle of the study statistically

Official Title
-----------------
Multicenter Randomized Study in Patients With Colorectal Cancer With Unresectable Metastases. Impact of Resection vs no Resection of the Primary Tumour as a Survival Factor

Conditions
-----------------
Colonic Cancer, Unresectable Metastasis Originating in Colonic Cancer

Intervention / Treatment
-----------------
* Procedure: Colonic resection
* Drug: Chemotherapy- scheme


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: colorectal cancer above to 12 cm from the anal verge unresectable synchronous metastases no contraindications for chemotherapy absence of peritoneal carcinomatosis, central nervous system o bone metastasis. performance status ECOG ≤ 2 (Eastern Cooperative Oncology Group) uncontrolled concomitant medical conditions that may compromise to chemotherapy significant symptomatic cardiac disease not pregnancy or breastfeeding Exclusion Criteria: Cases of rectal tumours below 12cm from anal verge, or locally advanced tumours invading blood vessels, nerves or bone. Multiple bone metastasis or central nervous system metastasis Other neoplastic disease in the 5 previous years, except squamous or basal cell skin carcinoma or cervical in situ carcinoma Significant heart disease (chronic congestive heart failure, symptomatic coronary disease) or myocardial infarction in the previous 6 months Peripheral neuropathy Patients who do not give informed consent

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

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

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

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

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: colonic resection<br>Arm A (experimental): surgery (complete tumoral resection; R0) followed by chemotherapy, regimen according to each center. | Procedure: Colonic resection<br>* Colonic cancer resection, R0 No surgical intervention on metastasis<br>Drug: Chemotherapy- scheme<br>* Chemotherapy, specified in each center with or without biological drugs<br>* Other names: CETUXIMAX / BEVACIZUMAB/PANITUMUMAB;|
| Active Comparator: Chemotherapy<br>Arm B (control): chemotherapy alone, regimen according to each center | Procedure: Colonic resection<br>* Colonic cancer resection, R0 No surgical intervention on metastasis<br>Drug: Chemotherapy- scheme<br>* Chemotherapy, specified in each center with or without biological drugs<br>* Other names: CETUXIMAX / BEVACIZUMAB/PANITUMUMAB;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the impact of overall survival in patients with unresectable metastatic colorectal cancer treated with chemotherapy alone vs surgery followed by chemotherapy. | The percentage of patients who are still alive for follow-up at 2 years after randomization. | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative morbidity and mortality. | Postoperative complications were classified according to the Dindo-Clavien classification. Mortality within 30 days after surgery | 30 days postoperatively | 
| Complications in patients treated with systemic chemotherapy | The toxicity will be evaluated and documented according to the CTCAE version 4.0. | up to 2 years | 
| Questionnaire Quality of life CR29 | Specific questionnaire for colon cancer | up to 2 years | 
| Study of possible survival factors | Identify factors that may influence patient survival before applying any treatment (demographics, clinicals and analitycal factors, tumor characteristics; ...) | up to 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colonic cancer, Metastasis