Systemic Chemotherapy With or Without Intraperitoneal Chemohyperthermia in Treating Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as leucovorin, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether systemic chemotherapy is more effective with or without intraperitoneal chemohyperthermia in treating patients with peritoneal carcinomatosis from colorectal cancer. PURPOSE: This randomized phase III trial is studying systemic chemotherapy to see how well it works compared with or without intraperitoneal chemohyperthermia in treating patients undergoing surgery for peritoneal carcinomatosis from colorectal cancer.

Detailed Description
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OBJECTIVES: Primary Compare overall survival of patients with peritoneal carcinoma of colorectal origin undergoing complete surgical resection and receiving systemic chemotherapy with versus without intraperitoneal chemohyperthermia. Secondary Evaluate recurrence-free survival of these patients. Evaluate treatment toxicities. Determine morbidity from surgical complications. Determine prognostic factors of survival. OUTLINE: This is a multicenter study. Patients are stratified according to participating center, residual tumor status (R0/R1 vs R2 ≤ 1 mm), prior regimens of systemic chemotherapy (first vs ≥ second), and preoperative systemic chemotherapy for metastatic disease (yes vs no). Patients are randomized to 1 of 2 treatment arms. All patients undergo maximal surgical resection of the tumor. Arm I: Patients receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and/or after surgery). Patients must stop systemic chemotherapy at least 1 month before receiving intraperitoneal chemohyperthermia (CHIP). If bevacizumab is given as neoadjuvant therapy, then systemic chemotherapy must be discontinued 6 weeks before beginning CHIP. Patients undergo CHIP comprising oxaliplatin intraperitoneally during surgery and hyperthermia for 30 minutes. Arm II: Patients undergo surgery and receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and after surgery). Tumor markers (ACE and CA 19-9) are assessed at baseline, at 1 month after surgery, and then at follow-up visits. After completion of study therapy, patients are followed at 1 and 3 months, every 3 months for 3 years, and then every 6 months for 2 years.

Official Title
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Phase III Study Evaluating the Use of Systemic Chemotherapy and Chemohyperthemia Intraperitoneal Preoperatively (CHIP) and After Maximum Resection of Peritoneal Carcinomatosis Originating With Colorectal Cancer

Conditions
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Colorectal Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin
* Procedure: hyperthermia treatment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed colorectal cancer Peritoneal carcinoma extension ≤ 25 (Sugarbaker Index) (determined intraoperatively) Planning to receive standard systemic chemotherapy Chemotherapy for metastatic cancer should be initiated 3 months after surgery No extraperitoneal metastases, including liver and lung metastasis No carcinomatosis of other origin besides colorectal, in particular appendical carcinomatosis Macroscopically complete resection (R1) or surgical reduction of tumor to a residual thickness ≤ 1 mm (R2) is possible PATIENT CHARACTERISTICS: WHO performance status 0-1 Life expectancy > 12 weeks ANC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Total bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 3 times ULN Alkaline phosphatase ≤ 3 times ULN Creatinine ≤ 1.25 times ULN Eligible for surgery No peripheral neuropathy > grade 3 Not pregnant or nursing No other cancer in the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix No inability to submit to follow-up medical testing for geographical, social, or psychological reasons Affiliated with a social security program Not deprived of liberty or under supervision PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemohyperthermia No concurrent participation in another study of first-line therapy for this cancer

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: Arm I<br>Patients undergo surgery and receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and after surgery). Patients also undergo CHIP comprising oxaliplatin intraperitoneally during surgery and hyperthermia for 30 minutes. | Drug: fluorouracil<br>* Given IV<br>Drug: leucovorin calcium<br>* Given IV<br>Drug: oxaliplatin<br>* Given during surgery<br>Procedure: hyperthermia treatment<br>* Given intraperitoneally during surgery<br>|
| Experimental: Arm II<br>Patients undergo surgery and receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and after surgery). | Drug: fluorouracil<br>* Given IV<br>Drug: leucovorin calcium<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | until 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival |  | until 3 years | 
| Toxicity by NCI CTCAE v.3.0 |  | until 5 years after surgery | 
| Morbidity from surgical complications (abdominal, extra-abdominal, aplasia) |  | until 2 months after surgery | 

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