Neoadjuvant FOLFOX6 + Cetuximab in Patients With Colorectal Cancer and Unresectable Liver Metastasis

Study Overview
=================
Brief Summary
-----------------
An innovative therapeutic strategy to increase the complete resection rate is of utmost importance in order to enhance survival in colorectal cancer patients with unresectable liver-only metastasis. Therefore, the investigators propose a prospective study of neoadjuvant chemotherapy using FOLFOX6 plus cetuximab to convert initially unresectable liver metastasis to potentially resectable disease.

Detailed Description
-----------------
We will include the patients with unresectable liver-only metastatic disease independent of EGFR status. The results of this study will show the resection rate with neoadjuvant treatment in patients with colorectal cancer with liver-only metastasis. Restaging including CT after #3, #6, #9, and #12 cycles of FOLFOX + Cetuximab If any time, patients have PD, Off-study SD, Continue study treatment until resectable, up to #12 cycles, PD, or toxicities PR or more, If resectable, go to surgery : resection of liver metastasis and primary tumor, if present If unresectable, continue until resectable, up to #12 cycles, PD, or toxicities Overall, a total of 12 cycles of treatment including neoadjuvant therapy will be given either before, after or without surgery. CT scans will be performed every 3 cycles during the first 12 cycles (6 months). After that, CT scans will be performed every 2 months for another 6 months, then every 3 months for 6 months, then once a year or earlier if a PD is probable. AEs will be evaluated once every cycle and during the CT evaluation visit.. Patients that can only undergo R1 resection or are unable to get surgery at all, will be evaluated regularly until PD. Radiofrequency ablation (RFA) may be allowed as a palliative local therapy in patients that are suitable for it. RFA is not considered equal to a resection.

Official Title
-----------------
A Phase II Study of Neoadjuvant FOLFOX6 Plus Cetuximab in Patients With Colorectal Cancer and Unresectable Liver Metastasis

Conditions
-----------------
Colorectal Cancer, Unresectable Liver Metastasis

Intervention / Treatment
-----------------
* Drug: FOLFOX6/cetuximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven colorectal cancer with metastatic lesion(s) in the liver that is (are) unresectable Age ≥ 18 ECOG performance 0 - 1 Adequate organ function ((hepatic transaminases ≤ 5x upper limit of normal, bilirubin < 2.0 x upper limit of normal, and creatinine ≤ 1.5x upper limit of normal, platelet > 100,000/ul, absolute neutrophil count ≥ 1,500/ul) At least one measurable lesion by RECIST criteria Written informed consent Exclusion Criteria: Resectable liver metastasis Extrahepatic metastases, regardless of their resectability Chronic active hepatitis or cirrhosis Prior therapy for metastatic disease Pregnant or lactating women Uncontrolled medical illnesses including medically uncontrolled infection, uncontrolled hypertension, unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months Previous adjuvant FOLFOX chemotherapy Prior adjuvant chemotherapy, if administered within 6 months before study entry Known hypersensitivity reaction to any of the components of study treatment Prior agents directed against EGFR Prior allergic reaction (known sensitivity) to chimerized or murine monoclonal antibody therapy Known alcohol or drug abuse Participation in another clinical study within the 30 days before registration Peripheral neuropathy > grade 1 Other previous malignancy with exception of a history of a previous curatively treated basal cell carcinoma of the skin of pre-invasive carcinoma of the cervix.

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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEO<br>NEO : Neoadjuvant therapy with FOLFOX6 plus cetuximab | Drug: FOLFOX6/cetuximab<br>* Neoadjuvant FOLFOX6/cetuximab<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate overall R0 resection rates following neoadjuvant FOLFOX6 plus cetuximab in patients with colorectal cancer and unresectable liver-only metastasis |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (according to RECIST) |  | 24 months | 
| Progression-free survival time |  | 24 months | 
| Overall survival timeToxicity profile (according to NCI CTCAE v3) |  | 24 months | 
| Correlative analyses between pretreatment EGFR, KRAS mutation and response rate/survival |  | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colorectal Cancer, Unresectable liver metastasis, FOLFOX6, Cetuximab, Neoadjuvant therapy