Biological Therapy With Combination Chemotherapy in Patients With Colorectal Cancer

Adjuvant Chemoimmunotherapy for Colorectal Cancer

RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining chemotherapy with biological therapy may kill more tumor cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of treatment using levamisole with treatment using interferon alfa and combination chemotherapy consisting of fluorouracil and leucovorin in patients with stage II or stage III colorectal cancer.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: recombinant interferon alfa; Drug: fluorouracil; Drug: leucovorin calcium; Drug: levamisole hydrochloride

Detailed Description

OBJECTIVES:

• Assess the efficacy of the addition of levamisole or alfa interferon to fluorouracil and leucovorin calcium (folinic acid) as an adjuvant treatment of intraperitoneal colorectal cancer.

OUTLINE: This is a three arm study. Patients are randomized to receive either levamisole, alfa interferon, or no treatment.

• Arm I: Patients receive levamisole PO for 3 days every 2 weeks for 6 months before and after surgery. Fluorouracil IV bolus and leucovorin calcium (folinic acid) IV over 1 hour are administered on days 1-5 every 4 weeks for 6 cycles after surgery.
• Arm II: Patients receive alfa interferon-2a SC on 3 alternate days for a week before surgery and for 6 months after surgery. Fluorouracil IV bolus and folinic acid IV over 1 hour are administered on days 1-5 every 4 weeks for 6 cycles after surgery.
• Arm III: Patients undergo surgery followed by fluorouracil IV bolus and folinic acid IV over 1 hour on days 1-5 every 4 weeks for 6 cycles.

Patients are followed every 3 months for 2 years, then every 6 months.

PROJECTED ACCRUAL: 350 patients per arm will be accrued for a total of 1,050 patients.

• Study Type: Interventional
• Enrollment (Anticipated): 1050
• Phase: Phase 3

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece, 57010
    • George Papanicolaou General Hospital
• Italy
  • Balsamo Cinisello, Italy, 20092
    • Ospedale Bassini
  • Bari, Italy, 70124
    • Universita Degli Studi di Bari Policlinico
  • Brescia, Italy, 25124
    • Spedali Civili
  • Cagliari, Italy, 09124
    • Ospedale Oncologico A. Businco
  • Cagliari, Italy, 09124
    • Cattedra di Oncologia Medica - Universita
  • Cagliari, Italy, 9100
    • Ospedale San Michele
  • Como, Italy, 22100
    • Ospedale Valduce
  • Como, Italy, 22100
    • Ospedale Sant Anna
  • Conselice, Italy, 48017
    • Ospedale Di Conselice
  • Cosenza, Italy, 87100
    • Ospedale Civile Cosenza
  • Crema, Italy, 26013
    • Ospedale Maggiore Crema
  • Cuneo, Italy, 12100
    • Ospedale Santa Croce
  • Feltre, Italy, 32100
    • Ospedale Civile Feltre
  • Ferrara, Italy, 44100
    • Università di Ferrara
  • Firenze, Italy, 50139
    • U.S.L. 10 Villa Ognissanti
  • Firenze (Florence), Italy, 1 (50134)
    • Universita Degli Studi di Firenze - Policlin. di Careggi
  • Firenze (Florence), Italy, 50134
    • Policlinico di Careggi
  • Genoa (Genova), Italy, 16132
    • Istituto Nazionale per la Ricerca sul Cancro
  • Genoa (Genova), Italy, 16132
    • Ospedale San Martino/Cliniche Universitarie Convenzionate
  • Genova (Genoa), Italy, 16128
    • Ospedale Galliera Oncologia
  • Gorgonzola, Italy, 20064
    • Ospedale Di Gorgonzola
  • Legnago, Italy, 37045
    • Ospedale Legnago USSL 21
  • Lodi, Italy, I-20075
    • Ospedale Maggiore Lodi
  • Lugo DI Romagna, Italy, 48022
    • Ospedale Umberto I
  • Magenta, Italy, 20013
    • U.S.S.L. 72 Magenta
  • Mantova, Italy, 46100
    • Carlo Poma Hospital
  • Melegnano, Italy, 20077
    • Ospedale Di Predabissi Melegnano
  • Merate, Italy, 22055
    • Azienda USSL NO 8
  • Messina, Italy, 98122
    • Instituto Di Oncologia
  • Mestre, Italy, 30174
    • Ospedale Civile Umberto I
  • Milano, Italy, 20100
    • Ospedale San Giuseppe
  • Milano, Italy, 20124
    • Consorzio Provinciale Antitubercolare
  • Milano, Italy, 20132
    • Istituto Scientifico H.S. Raffaele
  • Milano, Italy, 20142
    • Istituto Di Science Biomediche San Paolo
  • Milano, Italy, 20149
    • Casa Di Cura San Ambrogio
  • Milano (Milan), Italy, 20153
    • Ospedale San Carlo Borromeo
  • Milano (Milan), Italy, 20162
    • Ospedale Maggiore Ca Granda
  • Milano (Milan), Italy, 20157
    • Ospedale Luigi Sacco
  • Moncalieri, Italy, 10024
    • Ospedale Santa Croce
  • Monza, Italy, 20052
    • Nuovo Ospedale San Gerardo
  • Mortara, Italy, 27036
    • Ospedale Civile Asilo Vittoria
  • Naples, Italy, 80131
    • Istituto Nazionale per lo Studio e la Cura dei Tumori
  • Naples (Napoli), Italy, 80131
    • Federico II University Medical School
  • Naples (Napoli), Italy, 80131
    • Istituto Tumori/Fondazione Pascale
  • Napoli, Italy, 80131
    • Ospedale Vincenzo Monaldi
  • Napoli, Italy, 80139
    • Ospedale C. Ascalesi
  • Negrar, Italy, 37024
    • Ospedale Civile Negrar
  • Padova (Padua), Italy, 35128
    • Azienda Ospedaliera di Padova
  • Padua, Italy, 35128
    • University of Padua
  • Palermo, Italy, 90127
    • Ospedale Civico E Benefratelli
  • Parma, Italy, 43100
    • Ospedale Maggiore Parma
  • Parma, Italy, 43100
    • Ospedale Torrette University Ancona
  • Perugia, Italy, 06132
    • Ospedale Silvestrini
  • Pinerolo, Italy, 10064
    • Ospedale Agnelli
  • Ravenna, Italy, 48100
    • Ospedale Sta. Maria Delle Croci
  • Reggio Emilia, Italy, 42100
    • Azienda Ospedaliera
  • Rho, Italy, 20017
    • Ospedale Civile Rho
  • Rome, Italy, 00149
    • Ospedale Carlo Forlanini
  • Rome, Italy, 00161
    • Azienda Policlinico Umberto Primo
  • Rome, Italy, 00168
    • Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
  • Rome, Italy, 00128
    • Istituti Fisioterapici Ospitalieri - Roma
  • Rome, Italy, 00135
    • Ospedale San Filippo Neri
  • Rome, Italy, 00151
    • Ospedale S. Camillo-Forlanini
  • Rome, Italy, 00184
    • Policlinico Militare Celio
  • San Remo, Italy, 18038
    • ASL NO. 1 Imperiese
  • Saronno, Italy, 21047
    • Azienda USSL No 4
  • Sassari, Italy, 07100
    • Istituto Clinica Medica
  • Savigliano, Italy, 12038
    • Ospedale S.S. Annunziata
  • Sesto San Giovanni, Italy, 20099
    • Ospedale Sesto San Giovanni
  • Terni, Italy, 05100
    • Azienda Ospedaliera S. Maria
  • Thiene, Italy, 36016
    • Ospedale Generale Prov. Boldrini
  • Toino, Italy, 10100
    • Dispensario Igiene Sociale
  • Torino, Italy, 10126
    • Clinica Universita
  • Torino, Italy, 10126
    • Universita Torino
  • Trento, Italy, 38100
    • Ospedale S. Chiara
  • Trescore Balneario, Italy, 24069
    • Ospedale San Isidoro
  • Treviso, Italy, 31100
    • Ospedale General Regional Ca Foncello
  • Trieste, Italy
    • Ospedale Cattinara
  • Trieste, Italy, 34100
    • Ospedale Maggiore dell' Universita
  • Turin (TO), Italy, 10128
    • Cattedra di Immunologia Clinica
  • Udine, Italy, 33100
    • Università degli Studi di Udine
  • Varese, Italy, 21100
    • Ospedale di Circolo e Fondazione Macchi
  • Vicenza, Italy, 36100
    • Ospedale San Bortolo
• Korea, Republic of
  • Incheon, Korea, Republic of
    • Inha University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed stage T3-T4 N0 or T1-T4 N1-3 colorectal cancer
• No evidence of residual disease after surgery
• Tumor located above peritoneal reflection
• No distant metastases

PATIENT CHARACTERISTICS:

Age:

• 75 and under

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGPT less than 2 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No serious cardiac ischemia

Other:

• Adequate metabolic functions
• No prior neoplasm
• No prior/concurrent illness
• No insulin-dependent diabetes

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy for the current cancer

Chemotherapy

• No prior chemotherapy for the current cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for the current cancer

Surgery

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: European Institute of Oncology
• Investigators: Study Chair: Francesco Tonelli, MD, Universita Degli Studi di Florence - Policlinico di Careggi

Study record dates

Study Major Dates

• Study Start: November 1, 1991

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): September 20, 2013
• Last Update Submitted That Met QC Criteria: September 19, 2013
• Last Verified: November 1, 2005

More Information

Terms related to this study

• Keywords: stage III colon cancer; stage II rectal cancer; stage III rectal cancer; stage II colon 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; Anti-Infective Agents; Antiviral Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Adjuvants, Immunologic; Vitamins; Calcium-Regulating Hormones and Agents; Antiparasitic Agents; Antidotes; Vitamin B Complex; Antinematodal Agents; Anthelmintics; Interferons; Interferon-alpha; Fluorouracil; Leucovorin; Calcium; Levoleucovorin; Levamisole
• Other Study ID Numbers: CDR0000065728; CNR-TONE-01; EU-97011