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

Sponsor

UNICANCER (Other)

Overall Status

Completed

CT.gov ID

NCT00769405

Collaborator

(none)

264

Enrollment

Locations

Arms

13.2

Patients Per Site

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Colorectal Cancer Primary Peritoneal Cavity Cancer	Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: hyperthermia treatment	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

264 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Feb 1, 2008

Actual Primary Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I 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
Experimental: 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).	Drug: fluorouracil Given IV Drug: leucovorin calcium Given IV

Arm

Intervention/Treatment

Experimental: Arm I

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

Experimental: Arm II

Drug: fluorouracil

Given IV

Drug: leucovorin calcium

Given IV

Outcome Measures

Primary Outcome Measures

Overall survival [until 3 years]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Centre Paul Papin	Angers	France	49036
2	Hôpital Antoine Béclère	Clamart	France	92141
3	CHU Estaing	Clermont Ferrand	France	63003
4	Louis Mourier Hospital	Colombes Cedex	France	92701
5	Hopital Du Bocage	Dijon	France	21034
6	CHU de Grenoble - Hopital de la Tronche	Grenoble	France	38043
7	Centre Leon Berard	Lyon	France	69373
8	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier	France	34298
9	Centre Regional Rene Gauducheau	Nantes-Saint Herblain	France	44805
10	Hopital de l'Archet CHU de Nice	Nice	France	F-06202
11	Institut Curie	Paris	France	75005
12	Hopital Lariboisiere	Paris	France	75010
13	Hôpital Lariboisière	Paris	France	75010
14	Hopital Tenon	Paris	France	75970
15	Centre Hospitalier Lyon Sud	Pierre Benite	France	69495
16	Institut Jean Godinot	Reims	France	51056
17	Hopital Universitaire Hautepierre	Strasbourg	France	67098
18	Centre Hospitalier Regional de Purpan	Toulouse	France	31059
19	Centre Alexis Vautrin	Vandoeuvre-les-Nancy	France	54511
20	Institut Gustave Roussy	Villejuif	France	F-94805