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

Sponsored by:	Federation Nationale des Centres de Lutte Contre le Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00769405

Purpose

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.

Condition	Intervention	Phase
Colorectal Cancer Peritoneal Cavity Cancer	Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: hyperthermia treatment	Phase III

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Fluorouracil Oxaliplatin Calcium gluconate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
Official Title:	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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Recurrence-free survival [ Designated as safety issue: No ]
Toxicity by NCI CTCAE v.3.0 [ Designated as safety issue: Yes ]
Morbidity from surgical complications (abdominal, extra-abdominal, aplasia) [ Designated as safety issue: Yes ]

Estimated Enrollment:	264
Study Start Date:	February 2008

Arms	Assigned Interventions
Arm I: Experimental 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 Given IV Drug: leucovorin calcium Given IV Drug: oxaliplatin Given during surgery Procedure: hyperthermia treatment Given intraperitoneally during surgery
Arm II: Experimental 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 Given IV Drug: leucovorin calcium Given IV

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00769405

Locations

France
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Recruiting
Montpellier, France, 34298
Contact: Contact Person 33-4-6731-6015 francois.quenet@valdorel.fnclcc.fr

Sponsors and Collaborators

Federation Nationale des Centres de Lutte Contre le Cancer

Investigators

Principal Investigator:

Francois Quenet, MD

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000595024, FRE-FNCLCC-ACCORD-15/0608, EUDRACT-2006-006175-20, EU-20847
Study First Received:	October 8, 2008
Last Updated:	October 8, 2008
ClinicalTrials.gov Identifier:	NCT00769405
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
peritoneal carcinomatosis

Study placed in the following topic categories:

Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Leucovorin
Abdominal Neoplasms
Intestinal Diseases
Rectal Diseases
Dental Caries
Recurrence
Intestinal Neoplasms
Rectal neoplasm

Carcinoma
Calcium, Dietary
Oxaliplatin
Digestive System Diseases
Fluorouracil
Peritoneal Diseases
Gastrointestinal Neoplasms
Peritoneal Neoplasms
Rectal cancer
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Vitamin B Complex
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Growth Substances

Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Vitamins
Therapeutic Uses
Micronutrients

ClinicalTrials.gov processed this record on January 15, 2009