Second-look Surgery With or Without Intraperitoneal Chemotherapy in Treating Patients With Recurrent Colorectal Cancer

Study of Second Look Surgery With or Without Chemotherapy Intraperitoneally, in the Event of Risk of Intraperitoneal Recurrence

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy drugs in different ways may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of second-look surgery with or without intraperitoneal infusions of mitomycin and fluorouracil in treating patients who have colorectal cancer that is recurrent to the peritoneum.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer; Metastatic Cancer; Primary Peritoneal Cavity Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Drug: chemotherapy; Drug: mitomycin C; Procedure: conventional surgery; Procedure: laparoscopic surgery

Detailed Description

OBJECTIVES: I. Compare the effect of second look surgery with or without intraperitoneal mitomycin and fluorouracil on the 3 year survival rate of patients with colorectal cancer who are at high risk for peritoneal cavity cancer. II. Compare the quality of life of patients treated with these regimens. III. Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, risk group, presence of symptoms (yes vs no), and isolated disease (yes vs no). After primary surgery, all patients receive 6 months of chemotherapy consisting of leucovorin calcium IV followed by fluorouracil IV over 10 minutes on days 1-5 every 4 weeks. Patients then undergo second look surgery or laparoscopy at 8-12 months. Second look surgery or laparoscopy may be performed earlier if markers increase progressively for unknown reasons or symptoms of peritoneal cancer occur. Patients with recurrent disease that can be resected are randomized to one of two treatment arms. Patients with no residual disease or with unresectable disease are followed for survival. Arm I: Patients undergo complete resection of all detectable lesions followed immediately by intraperitoneal (IP) mitomycin on day 0 and fluorouracil IP on days 1-4. Patients also receive systemic chemotherapy consisting of leucovorin calcium IV over 2 hours and fluorouracil IV bolus, followed by fluorouracil IV over 22 hours on days 1 and 2. Systemic chemotherapy repeats every 2 weeks for 6 months. Arm II: Patients undergo complete or partial resection and then receive systemic chemotherapy as in arm I. Quality of life is assessed at baseline and then every 4 months for 3 years. All patients (including nonrandomized patients) are followed every 4 months for 3 years.

PROJECTED ACCRUAL: A total of 152 patients (76 randomized) will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Liege, Belgium, B-4000
    • CHU Sart-Tilman
• France
  • Besancon, France, 25030
    • CHR de Besancon - Hopital Jean Minjoz
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Boulogne Billancourt, France, F-92104
    • CHU Ambroise Paré
  • Dijon, France, 21033
    • Centre Hospitalier Universitaire de Dijon
  • Lille, France, 59037
    • Centre Hospitalier Regional de Lille
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Marseille, France, 13385
    • CHU de la Timone
  • Marseille, France, 13273
    • Institut J. Paoli and I. Calmettes
  • Montpellier, France, 34298
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
  • Nantes, France, 44093
    • CHR Hotel Dieu
  • Nantes-Saint Herblain, France, 44805
    • CRLCC Nantes - Atlantique
  • Nice, France, F-06202
    • Hopital L'Archet - 2
  • Nimes, France, 30000
    • C.H.R. de Nimes - Hopital Caremeau
  • Orleans, France, 45067
    • CHR D'Orleans - Hopital de la Source
  • Reims, France, 51092
    • Centre Hospitalier Universitaire
  • Strasbourg, France, 67085
    • Centre Paul Strauss
  • Villejuif, France, F-94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Primary diagnosis of adenocarcinoma of the colon or rectum and meeting one of the following risk criteria during the primary surgery: Perforated bowel (spontaneous or not) Occlusion Peritoneal deposits Invasion of serosa of more than 4 cm diameter Concurrent ovarian metastases Randomization eligibility: Presence of proven recurrent peritoneal disease (only one micronodule of 1 mm sufficient) at second look laparotomy Total resection of macroscopic lesions possible (local recurrence, lymph node or hepatic metastases)

PATIENT CHARACTERISTICS: Age: 70 and under Performance status: Not specified Life expectancy: Not specified Hematopoietic: WBC at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Not specified Renal: Creatinine no greater than 1.4 mg/dL Cardiovascular: No cardiac condition that would increase surgical risk Pulmonary: No pulmonary condition that would increase surgical risk Other: No other condition that would increase surgical risk No other malignancy within the past 5 years except basal cell skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy Radiotherapy: No concurrent anticancer radiotherapy Surgery: See Disease Characteristics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: UNICANCER
• Investigators: Study Chair: Dominique Elias, MD, Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 1999
• Primary Completion (Actual): October 24, 2000
• Study Completion (Actual): October 1, 2003

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: March 23, 2004
• First Posted (Estimate): March 24, 2004

Study Record Updates

• Last Update Posted (Actual): February 17, 2021
• Last Update Submitted That Met QC Criteria: February 15, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; adenocarcinoma of the colon; recurrent colon cancer; recurrent rectal cancer; liver metastases; primary peritoneal cavity cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Alkylating Agents; Micronutrients; Antibiotics, Antineoplastic; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Calcium; Levoleucovorin; Mitomycins; Mitomycin
• Other Study ID Numbers: CDR0000067833; FRE-FNCLCC-97018; EU-20010