Neoadjuvant FOLFOX Chemotherapy for Patients With Locally Advanced Colon Cancer

Study Overview
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Brief Summary
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The main cause of recurrence after surgical treatment of colon cancer is distant metastasis. Neoadjuvant chemotherapy has potential benefits of improving the effectiveness of chemotherapy. Preoperative chemotherapy may eradicate microscopic metastatic cancer cells earlier than adjuvant chemotherapy, reduce cancer cell spillage during surgery, and lessen the invasiveness of surgical resection. This randomized multicenter phase III trial is assessing whether preoperative chemotherapy improves oncologic outcomes of patients with locally advanced colon cancer.

Official Title
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Neoadjuvant Chemotherapy for Non-metastatic Locally Advanced Colon Cancer: A Prospective Multicenter Randomized Controlled Trial

Conditions
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Colon Cancer

Intervention / Treatment
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* Drug: Neoadjuvant FOLFOX
* Drug: Conventional adjuvant FOLFOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed colon adenocarcinoma (> 15 cm from the anal verge) Radiologic T3/T4 and high risk features by CT scan No metastasis on CT or PET(positron emission computed tomography) Age ≥ 18 and ≤ 70 years ECOG (Eastern Cooperative Oncology Group) performance status 0-1 No history of colorectal cancer within 5 years No history of chemotherapy Patients with childbearing potential should use effective contraception during the study and the following 6 months Adequate bone marrow function : white blood cell count of 2 x 109/L or more with neutrophils of1.5 x 109/L or more, platelet count of 100 x 109/L or more, hemoglobin of 9 g/dL (5,6 mmol/l) or more Adequate hepatobiliary function : total bilirubin of 0.4 mg/dl or less, ASAT (aspartate aminotransferase) and ALAT (alanine aminotransferase) of 2.5 x ULN (upper limits of normal) or less, Alkaline phosphatase of 1.5 x ULN or less Adequate renal function : GFR (Glomerular Filtration Rate) > 50ml/min by Wright or Cockcroft formula Signed written informed consent obtained prior to any study specific screening procedures Exclusion Criteria: Age > 70 years and < 18 years Rectal cancer : 15 cm or less from the anal verge Complicated colon cancer (complete obstruction, perforation, bleeding) Metastatic colon cancer Known hypersensitivity reaction to any of the components of study treatments Inflammatory bowel disease Hereditary nonpolyposis colorectal cancerHNPCC, familial Adenomatous Polyposis Clinically relevant coronary artery disease or history of myocardial infarction in the last 6 months, high risk of uncontrolled arrhythmia Galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption Pregnancy or breast-feeding period Serious non-healing wound or bone fracture Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent Any significant disease which, in the investigator's opinion, would exclude the patient from the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant FOLFOX<br>4 cycles of FOLFOX (Folinic acid, fluorouracil and oxaliplatin) neoadjuvant followed by surgery and 8 cycles of FOLFOX | Drug: Neoadjuvant FOLFOX<br>* 4 cycles of FOLFOX neoadjuvant chemotherapy and 8 cycles of postoperative chemotherapy<br>|
| Active Comparator: Conventional adjuvant FOLFOX<br>surgery followed by 12 cycles of FOLFOX | Drug: Conventional adjuvant FOLFOX<br>* 12 cycles of postoperative FOLFOX chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse free survival after randomization |  | 3 years after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 3 year after randomization | 
| Radiological assessment of response to neoadjuvant treatment |  | 6 months after surgery | 
| Pathological assessment of response to neoadjuvant treatment | Replacement of the tumor by fibrous or fibro-inflammatory granulation tissue | 1 months after surgery | 
| Surgical complication |  | 60 days after surgery | 
| Length of hospital stay |  | 60 days after surgery | 
| Quality of life (EORTC QLQ-C30) | QLQ (quality of life questionnaire) | before treatment, before surgery, 3 months after surgery, 6 months after surgery, 1 year after surgery | 
| Quality of life (EORTC QLQ-C38) |  | before treatment, before surgery, 3 months after surgery, 6 months after surgery, 1 year after surgery | 
| Toxicity of chemotherapy | Toxicity : incidence of chemotherapy-related adverse events according to CTCAE (Common Terminology Criteria for Adverse Events) v4.0 | 1 year | 
| Incidence of completion of chemotherapy |  | 1 year | 
| Accuracy of CT staging |  | 1 year | 
| Total cycles of perioperative chemotherapy |  | 1 year | 
| Pathological tumor stage | Colon cancer stage by AJCC 8th edition | 1 month after surgery |