Clinical trial NCT00769405: Systemic Chemotherapy With or Without Intraperitoneal Chemohyperthermia in Treating Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Primary Peritoneal Cavity Cancer
Keywords: recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
peritoneal carcinomatosis
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2008-10-09
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Overall survival
timeFrame: until 3 years
Secondary outcomes:
measure: Recurrence-free survival
timeFrame: until 3 years
measure: Toxicity by NCI CTCAE v.3.0
timeFrame: until 5 years after surgery
measure: Morbidity from surgical complications (abdominal, extra-abdominal, aplasia)
timeFrame: until 2 months after surgery
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Paul Papin
city: Clamart
country: France
facility: Hôpital Antoine Béclère
city: Clermont Ferrand
country: France
facility: CHU Estaing
city: Colombes Cedex
country: France
facility: Louis Mourier Hospital
city: Dijon
country: France
facility: Hopital Du Bocage
city: Grenoble
country: France
facility: CHU de Grenoble - Hopital de la Tronche
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nantes-Saint Herblain
country: France
facility: Centre Regional Rene Gauducheau
city: Nice
country: France
facility: Hopital de l'Archet CHU de Nice
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Hôpital Lariboisière
city: Paris
country: France
facility: Hopital Tenon
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Reims
country: France
facility: Institut Jean Godinot
city: Strasbourg
country: France
facility: Hopital Universitaire Hautepierre
city: Toulouse
country: France
facility: Centre Hospitalier Regional de Purpan
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Institut du Cancer de Montpellier - Val d'Aurelle
name: Francois Quenet, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Quenet F, Elias D, Roca L, Goere D, Ghouti L, Pocard M, Facy O, Arvieux C, Lorimier G, Pezet D, Marchal F, Loi V, Meeus P, Juzyna B, de Forges H, Paineau J, Glehen O; UNICANCER-GI Group and BIG Renape Group. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):256-266. doi: 10.1016/S1470-2045(20)30599-4. Epub 2021 Jan 18.