Chemotherapy and Cetuximab in Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) together with cetuximab may kill more tumor cells. PURPOSE: This phase II trial is studying how well chemotherapy given together with cetuximab works in treating patients undergoing surgery to remove peritoneal carcinomatosis from colorectal cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the efficacy of systemic chemotherapy and cetuximab, in terms of progression-free survival at 3 years, in patients with completely resected peritoneal carcinomatosis of colorectal origin. Secondary Determine the therapeutic strategy among patients who are or are not fit to receive chemotherapy. Determine progression-free survival at 5 years and overall survival at 3 and 5 years in these patients. Determine the overall tolerability (mortality, morbidity) of this regimen, including surgery, in these patients. OUTLINE: This is a multicenter study. Patients undergo complete resection of the peritoneal carcinomatosis. Beginning 4-8 weeks after surgery, patients receive cetuximab IV over 2.5 hours. Patients also receive FOLFOX chemotherapy comprising oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours. Treatment repeats every 2 weeks for up to 12 courses. After completion of study therapy, patients are followed every 4 months for 2 years and then every 6 months for 3 years.

Official Title
-----------------
Clinical Phase II Study Evaluating Systemic Chemotherapy in Combination With Cetuximab as Adjuvant Treatment in Patients With Completely Surgically Resected Peritoneal Carcinomatosis of Colorectal Origin

Conditions
-----------------
Colorectal Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
-----------------
* Biological: cetuximab
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin
* Procedure: adjuvant therapy
* Procedure: therapeutic conventional surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed colorectal adenocarcinoma meeting the following criteria: Exclusively peritoneal carcinomatosis (no other metastases) Resectable disease Primary tumor may be same in the same location as another synchronous carcinomatosis Patients with metastatic disease who have been in complete remission for more than 1 year are eligible regardless of prior chemotherapy PATIENT CHARACTERISTICS: WHO performance status 0-2 Life expectancy ≥ 12 weeks ANC ≥ 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Hemoglobin ≥ 10 g/dL Bilirubin ≤ 1.25 times upper limit of normal (ULN) AST and ALT ≤ 3 times ULN Creatinine ≤ 1.25 times ULN Creatinine clearance ≥ 30 mL/min Not pregnant or nursing Fertile patients must use effective contraception No allergy, hypersensitivity, or other contraindication to leucovorin calcium, oxaliplatin, or fluorouracil No other noncancerous disease that would preclude study therapy Good nutritional status No sensitive peripheral neuropathy with functional impairment No hypoplasia or bone marrow failure No clinically significant cardiovascular disease within the past year (e.g., unstable angina or myocardial infarction) No other cancer within the past 5 years unless in complete remission with the exception of cervical carcinoma in situ or basal cell cancer No patients deprived of liberty or under supervision No psychological, social, familial, or geographical reasons prohibiting follow-up PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 1 year since prior adjuvant chemotherapy, including prior therapy with oxaliplatin and/or cetuximab No prophylactic phenytoin (Dihydan®, Dilantin®) No prior yellow fever vaccine More than 1 month since participation in another study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Combination Chemotherapy and Cetuximab in Treating Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy + Cetuximab<br>Surgery + Chemotherapy + Cetuximab | Biological: cetuximab<br> <br> Drug: fluorouracil<br> <br> Drug: leucovorin calcium<br> <br> Drug: oxaliplatin<br> <br> Procedure: adjuvant therapy<br> <br> Procedure: therapeutic conventional surgery<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression-free Survival (PFS) Time | Progression-free survival time is defined as the time from the date of surgery to the date of progression (as per RECIST v1.1) or death of any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Since surgery, up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day Mortality Rate | Rate of deaths observed within 30 days of surgery | from the date of surgery up to 30 days | 
| Mean Number of Adverse Events Per Patient, Within 30 Days of Surgery |  | from the date of surgery up to 30 days | 
| Overall Survival (OS) Time | OS is the delay between surgery and death | from surgery, up to five years. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the colon, recurrent colon cancer, stage IV colon cancer, adenocarcinoma of the rectum, recurrent rectal cancer, stage IV rectal cancer, peritoneal carcinomatosis