Irinotecan With or Without Oxaliplatin in Treating Patients With Metastatic Colorectal Cancer

A Multicenter, Open-Label, Randomized, Two-Arm Study of Irinotecan (CPT-11) Versus the Combination of Oxaliplatin + Irinotecan (CPT-11) as Second-Line Treatment of Metastatic Colorectal Carcinoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if irinotecan is more effective with or without oxaliplatin in treating metastatic colorectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of irinotecan with or without oxaliplatin in treating patients who have metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: irinotecan hydrochloride; Drug: oxaliplatin

Detailed Description

OBJECTIVES:

• Compare the overall survival of patients with metastatic colorectal cancer treated with irinotecan with or without oxaliplatin.
• Compare the response rate, time to tumor-related worsening of symptoms, time to disease progression, onset and duration of responses, and duration of disease stabilization in these patients treated with these regimens.
• Compare the safety of these regimens in these patients.

OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to Karnofsky performance status (50-60% vs 70-100%), number of metastatic organs involved (1 vs 2 or more), lactic dehydrogenase (no greater than 1.5 times upper limit of normal (ULN) vs greater than 1.5 times ULN), and prior fluorouracil chemotherapy (adjuvant vs first-line treatment for metastatic disease). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive irinotecan IV over 90 minutes on day 1.
• Arm II: Patients receive oxaliplatin IV over 120 minutes followed by irinotecan IV over 30 minutes on day 1.

Courses repeat in each arm every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days, every 4 weeks for 3 months, and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 596 patients (298 per arm) will be accrued for this study within 18 months.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Aracaiu-SE, Brazil, CEP: 49094-970
    • Hospital Joao Alves Fiho
  • Belo Horizonte-MG, Brazil, CEP: 30180-060
    • Hospital Socor
  • Curitiba-PR, Brazil, CEP: 81520-060
    • Hospital Erastos Gaertner
  • Rio de Janeiro, Brazil, 20230-130
    • Instituto Nacional de Câncer
  • Rio de Janeiro, Brazil, CEP: 22260-020
    • Oncologistas Associados
  • Sao Paulo, Brazil, CEP: 01509-010
    • Hospital do Cancer A C Comargo
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-003
      • Porto Alegre Hospital
  • Sao Paulo
    • Sorocaba, Sao Paulo, Brazil, 18030-200
      • Instituto de Oncologia de Soracaba
• Canada
  • St. Jerome Quebec, Canada, JYZ 5T3
    • Zoom International Incoporated
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center - Calgary
    • Edmonton, Alberta, Canada, T6G 2R7
      • University of Alberta
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Cancer Centre
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital, Barrie
    • London, Ontario, Canada, N6A 4L6
      • Cancer Care Ontario-London Regional Cancer Centre
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Regional Cancer Centre
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeastern Ontario Regional Cancer Centre, Sudbury
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Regional Cancer Centre
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital - Toronto
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hopital Charles LeMoyne
    • Laval, Quebec, Canada, H7M 3L9
      • Cite de La Sante de Laval
    • Levis, Quebec, Canada, G6V 3Z1
      • L'Hotel Dieu de Levis
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital du Sacre-Coeur de Montreal
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital - Montreal
    • Quebec City, Quebec, Canada, G1R 2J6
      • Centre Hospitalier Universitaire de Quebec
    • Sainte Foy, Quebec, Canada, GIV 4G2
      • Centre Hospitalier de L'Universitaire de Quebec, Pavillon CHUL
    • Ste-Foy, Quebec, Canada, G1V 4G5
      • L'Hopital Laval
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• Czech Republic
  • Ceske Budejovice, Czech Republic, 370 01
    • Centre of Clinical Oncology and Radiation Oncology
  • Hradec Kralove, Czech Republic, 500 02
    • Charles University Hospital
  • Prague, Czech Republic, 128 08
    • Onkologicka Klinka A Onkologicka Lab
  • Praha, Czech Republic, 150 06
    • Fakultni nemocnice v Motole
• Hungary
  • Budapest, Hungary, 1125
    • National Institute of Oncology
  • Budapest, Hungary, 1082
    • Semmelweis University
  • Budapest, Hungary, H-1032
    • Fovarosi Onkormanyzat Szent Margit Korhaz, Okologia
  • Budapest, Hungary, H-1097
    • Szent Laszlo Korhaz
  • Budapest, Hungary, H-1134
    • Kozponti Honvedkorhaz I. Belgyogyaszat
  • Debrecen, Hungary, H-4012
    • Debreceni Egyetem Onkologiai Tanzek
  • Gydr, Hungary, h-9024
    • Petz Aladar County Hospital
• Poland
  • Gliwice, Poland, 44-101
    • Maria S. Curie Memorial Institute
  • Krakow (Cracow), Poland, 31-826
    • Jagiellonian University
  • Lodz, Poland, 93509
    • Institute of Oncology
  • Poznan, Poland, 61-866
    • Wielkopolskie Centrum Onkologii Oddzial Chemioterapii
• United Kingdom
  • England
    • Guildford, England, United Kingdom, GU2 5XX
      • St. Luke's Cancer Center
    • London, England, United Kingdom, SE1 9RT
      • Guy's and St. Thomas' Hospitals NHS Trust
    • London, England, United Kingdom, W6 8RF
      • Charing Cross Hospital
    • London, England, United Kingdom, EC1A 7BE
      • St. Bartholomew's Hospital
    • Maidstone, England, United Kingdom, ME16 9QQ
      • Maidstone Hospital
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital N.H.S. Trust
    • Plymouth, England, United Kingdom, PL6 8DH
      • Derriford Hospital
    • Sheffield, England, United Kingdom, S1O 2SJ
      • Weston Park Hospital
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden Hospital
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Comprehensive Cancer Institute of Huntsville
    • Mobile, Alabama, United States, 36688
      • Oncology Center at Providence Park
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Arizona Clinical Research Center
  • California
    • Covina, California, United States, 91722
      • Citrus Valley Medical Center
    • Greenbrae, California, United States, 94904-2007
      • California Cancer Care, Inc.
    • Los Angeles, California, United States, 90057
      • Kenmar Research Institute
    • Los Angeles, California, United States, 90048
      • Tower Hematology Oncology Medical Group
    • Los Angeles, California, United States, 90067
    • Orange, California, United States, 92868
      • Medical Oncology Care Associates
    • Oxnard, California, United States, 93030
      • P.M.K. Medical Group, Inc.
    • Rancho Mirage, California, United States, 92270
      • Cancer and Blood Institute of the Desert
    • San Diego, California, United States, 92120
      • Kaiser Permanente-Southern California Permanente Medical Group
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute
    • Vallejo, California, United States, 94589
      • Kaiser Permanente Medical Center - Vallejo
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Center
    • Denver, Colorado, United States, 80205
      • Colorado Permanente Medical Group, P.C.
    • Denver, Colorado, United States, 80220
      • University of Colorado Cancer Center
  • Connecticut
    • Norwalk, Connecticut, United States, 06856
      • Whittingham Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University Medical Center
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Comprehensive Cancer Care Specialists of Boca Raton
    • Boca Raton, Florida, United States, 33486
      • Center for Hematology-Oncology
    • Fort Lauderdale, Florida, United States, 33308
      • Southeast Florida Hematology-Oncology Group
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Gainesville, Florida, United States, 32610-100277
      • Shands Hospital and Clinics, University of Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Science Center - Jacksonville
    • Jacksonville, Florida, United States, 32207
      • Hematology and Oncology Associates of Jacksonville
    • Lakeland, Florida, United States, 33804
      • Lakeland Regional Medical Center
    • Leesburg, Florida, United States, 34748
      • Lake Heart and Cancer Medical Center
    • Miami, Florida, United States, 33176
      • Oncology-Hematology Group of South Florida
    • Orlando, Florida, United States, 32804
      • Hematology and Oncology Consultants, P.A.
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology/Oncology Associates
    • Tamarac, Florida, United States, 33321
      • Oncology & Hematology Associates of West Broward
    • Tampa, Florida, United States, 33613
      • University Community Hospital
    • Titusville, Florida, United States, 32796
      • Hematology and Oncology Consultants
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • North Idaho Cancer Center
  • Illinois
    • Arlington Heights, Illinois, United States, 60004
      • Northwest Medical Specialists, P.C.
    • Aurora, Illinois, United States, 60506
      • Dreyer Medical Clinic
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Faculty Foundation
  • Indiana
    • New Albany, Indiana, United States, 47150
      • Cancer Care Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0084
      • Albert B. Chandler Medical Center, University of Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Cancer Institute
    • Louisville, Kentucky, United States, 40202
      • Norton Healthcare Pavilion
    • Louisville, Kentucky, United States, 40206
      • Veterans Affairs Medical Center - Louisville
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70806
      • Baton Rouge General Medical Center
    • Lafayette, Louisiana, United States, 70506
      • Louisiana Oncology Associates
    • Metairie, Louisiana, United States, 70006
      • Doctors Hospital of Jefferson
    • New Orleans, Louisiana, United States, 70112
      • Stanley Scott Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center and Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
      • Medical Center of Boston
    • Pittsfield, Massachusetts, United States, 01201
      • Berkshire Hematology Oncology, P.C.
  • Michigan
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Flint, Michigan, United States, 48532
  • Minnesota
    • Roseville, Minnesota, United States, 55113
      • Parker Hughes Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Jackson Oncology Associates, PLLC
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Veterans Affairs Medical Center - Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center
    • Saint Louis, Missouri, United States, 63141
      • St. John's Mercy Medical Center
    • St. Charles, Missouri, United States, 63301
      • Missouri Cancer Care, P.C.
  • Montana
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Missoula, Montana, United States, 59807-7609
      • Western Montana Clinic
  • New Jersey
    • Somerville, New Jersey, United States, 08876
      • Somerset Medical Center
    • Voorhees, New Jersey, United States, 08043
      • Cooper Cancer Institute
  • New York
    • Albany, New York, United States, 12208
      • Veterans Affairs Medical Center - Albany
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center
    • Fresh Meadows, New York, United States, 11365
      • Queens Medical Associates, PC
    • Jamaica, New York, United States, 11432
      • Queens Hospital Center
    • Rochester, New York, United States, 14623
      • Interlakes Oncology/Hematology PC
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center, UNC
    • Raleigh, North Carolina, United States, 27609
      • Raleigh Hematology/Oncology Associates - Wake Practice
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Hematology-Oncology Associates
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43235
      • Hematology Oncology Consultants Inc
  • Oregon
    • Bend, Oregon, United States, 97701
      • Bend Memorial Clinic
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente - Portland
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17105-8700
      • Pinnacle Health Hospitals
    • Meadowbrook, Pennsylvania, United States, 18974
      • Abington Hematology Oncology Associates, Incorporated
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Cancer Center
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Oncology Hematology Associates
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Cancer Institute
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Lifespan: The Miriam Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Cancer Centers of the Carolinas
    • Greenville, South Carolina, United States, 27834
      • Physicians East - Quadrangle
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Health Systems
    • Knoxville, Tennessee, United States, 37901
      • Baptist Regional Cancer Center - Knoxville
    • Memphis, Tennessee, United States, 38119
      • Memphis Cancer Center
    • Memphis, Tennessee, United States, 38117
      • West Clinic
    • Nashville, Tennessee, United States, 37232-6307
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37205
      • Tennessee Oncology, P.L.L.C.
  • Texas
    • Austin, Texas, United States, 78759
      • Lone Star Oncology
    • Dallas, Texas, United States, 75230
      • Center for Oncology Research and Treatment, Medical City Hospital
    • San Antonio, Texas, United States, 78205
      • Baptist Health System Cancer Program
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Cancer Center at the University of Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Hematology-Oncology Associates of Frederiksburg, Inc.
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Advanced Health Care
    • Wausau, Wisconsin, United States, 54401
      • UW Cancer Center Wausau Hospital
  • Wyoming
    • Laramie, Wyoming, United States, 82070
      • Irving Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum
• Metastatic or recurrent disease that is not amenable to potentially curative treatment
• Progressive or recurrent disease during or after 1, and only 1, regimen of fluorouracil with or without leucovorin calcium or during or within 6 months after adjuvant chemotherapy with fluorouracil and leucovorin calcium

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 50-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT/SGPT no greater than 2 times ULN (no greater than 5 times ULN if liver metastases present)
• Alkaline phosphatase no greater than 2 times ULN (no greater than 5 times ULN if liver metastases present)

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No unstable angina
• No New York Heart Association class III or IV congestive heart failure
• No serious cardiac arrhythmia
• No history of cardiac toxicity from fluorouracil/leucovorin calcium
• No myocardial infarction within past 6 months

Pulmonary:

• No interstitial pneumonia or extensive and symptomatic fibrosis of the lung

Other:

• No uncontrolled predisposing colonic or small bowel disorder
• No prior chronic enteropathy, chronic diarrhea, or unresolved bowel obstruction/subobstruction
• No diabetes
• No active infection
• No known current peripheral neuropathy
• No concurrent active cancer except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No intolerance of appropriate antiemetics
• No history of anaphylaxis or potential intolerance to atropine sulfate or loperamide
• Not pregnant or nursing
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy
• No prior irinotecan or oxaliplatin
• No other prior chemotherapy agents except fluorouracil with or without leucovorin calcium as first-line therapy for metastatic disease or in the adjuvant setting

Endocrine therapy:

• Not specified

Radiotherapy:

• Prior radiotherapy to non-target lesions allowed
• No prior radiotherapy to target lesions unless disease progression is documented within the radiation port
• At least 3 weeks since prior radiotherapy

Surgery:

• At least 4 weeks since prior major surgical procedure and recovered
• Prior surgery for primary tumor or metastasis allowed

Other:

• At least 30 days since prior investigational drug
• No concurrent investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Chair: Daniel G. Haller, MD, Abramson Cancer Center of The University of Pennsylvania

Publications and helpful links

General Publications

• Haller DG, Rothenberg ML, Wong AO, Koralewski PM, Miller WH Jr, Bodoky G, Habboubi N, Garay C, Olivatto LO. Oxaliplatin plus irinotecan compared with irinotecan alone as second-line treatment after single-agent fluoropyrimidine therapy for metastatic colorectal carcinoma. J Clin Oncol. 2008 Oct 1;26(28):4544-50. doi: 10.1200/JCO.2008.17.1249.

Study record dates

Study Major Dates

• Study Start: December 1, 2000
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: March 3, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 19, 2013
• Last Update Submitted That Met QC Criteria: December 18, 2013
• Last Verified: October 1, 2002

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Oxaliplatin; Irinotecan
• Other Study ID Numbers: CDR0000068524; SANOFI-EFC4585