Clinical trial NCT00012389: Irinotecan With or Without Oxaliplatin in Treating Patients With Metastatic Colorectal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Comprehensive Cancer Institute of Huntsville
state: Alabama
city: Mobile
country: United States
facility: Oncology Center at Providence Park
state: Alabama
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Covina
country: United States
facility: Citrus Valley Medical Center
state: California
city: Greenbrae
country: United States
facility: California Cancer Care, Inc.
state: California
city: Los Angeles
country: United States
facility: Tower Hematology Oncology Medical Group
state: California
city: Los Angeles
country: United States
facility: Kenmar Research Institute
state: California
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
facility: Medical Oncology Care Associates
state: California
city: Oxnard
country: United States
facility: P.M.K. Medical Group, Inc.
state: California
city: Rancho Mirage
country: United States
facility: Cancer and Blood Institute of the Desert
state: California
city: San Diego
country: United States
facility: Kaiser Permanente-Southern California Permanente Medical Group
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center - Vallejo
state: California
city: Denver
country: United States
facility: Colorado Permanente Medical Group, P.C.
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Norwalk
country: United States
facility: Whittingham Cancer Center
state: Connecticut
city: Washington
country: United States
facility: George Washington University Medical Center
state: District of Columbia
city: Boca Raton
country: United States
facility: Comprehensive Cancer Care Specialists of Boca Raton
state: Florida
city: Boca Raton
country: United States
facility: Center for Hematology-Oncology
state: Florida
city: Fort Lauderdale
country: United States
facility: Southeast Florida Hematology-Oncology Group
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Gainesville
country: United States
facility: Shands Hospital and Clinics, University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Hematology and Oncology Associates of Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Science Center - Jacksonville
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Medical Center
state: Florida
city: Leesburg
country: United States
facility: Lake Heart and Cancer Medical Center
state: Florida
city: Miami
country: United States
facility: Oncology-Hematology Group of South Florida
state: Florida
city: Orlando
country: United States
facility: Hematology and Oncology Consultants, P.A.
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology/Oncology Associates
state: Florida
city: Tamarac
country: United States
facility: Oncology & Hematology Associates of West Broward
state: Florida
city: Tampa
country: United States
facility: University Community Hospital
state: Florida
city: Titusville
country: United States
facility: Hematology and Oncology Consultants
state: Florida
city: Coeur d'Alene
country: United States
facility: North Idaho Cancer Center
state: Idaho
city: Arlington Heights
country: United States
facility: Northwest Medical Specialists, P.C.
state: Illinois
city: Aurora
country: United States
facility: Dreyer Medical Clinic
state: Illinois
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: New Albany
country: United States
facility: Cancer Care Center
state: Indiana
city: Lexington
country: United States
facility: Albert B. Chandler Medical Center, University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Kentuckiana Cancer Institute
state: Kentucky
city: Louisville
country: United States
facility: Norton Healthcare Pavilion
state: Kentucky
city: Louisville
country: United States
facility: Veterans Affairs Medical Center - Louisville
state: Kentucky
city: Baton Rouge
country: United States
facility: Baton Rouge General Medical Center
state: Louisiana
city: Lafayette
country: United States
facility: Louisiana Oncology Associates
state: Louisiana
city: Metairie
country: United States
facility: Doctors Hospital of Jefferson
state: Louisiana
city: New Orleans
country: United States
facility: Stanley Scott Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center and Cancer Center
state: Maryland
city: Boston
country: United States
facility: Medical Center of Boston
state: Massachusetts
city: Pittsfield
country: United States
facility: Berkshire Hematology Oncology, P.C.
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Flint
country: United States
state: Michigan
city: Roseville
country: United States
facility: Parker Hughes Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: Jackson Oncology Associates, PLLC
state: Mississippi
city: Kansas City
country: United States
facility: Veterans Affairs Medical Center - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: St. John's Mercy Medical Center
state: Missouri
city: St. Charles
country: United States
facility: Missouri Cancer Care, P.C.
state: Missouri
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Missoula
country: United States
facility: Western Montana Clinic
state: Montana
city: Somerville
country: United States
facility: Somerset Medical Center
state: New Jersey
city: Voorhees
country: United States
facility: Cooper Cancer Institute
state: New Jersey
city: Albany
country: United States
facility: Veterans Affairs Medical Center - Albany
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Fresh Meadows
country: United States
facility: Queens Medical Associates, PC
state: New York
city: Jamaica
country: United States
facility: Queens Hospital Center
state: New York
city: Rochester
country: United States
facility: Interlakes Oncology/Hematology PC
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Hematology/Oncology Associates - Wake Practice
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Hematology-Oncology Associates
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Hematology Oncology Consultants Inc
state: Ohio
city: Bend
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Portland
country: United States
facility: Kaiser Permanente - Portland
state: Oregon
city: Harrisburg
country: United States
facility: Pinnacle Health Hospitals
state: Pennsylvania
city: Meadowbrook
country: United States
facility: Abington Hematology Oncology Associates, Incorporated
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan: The Miriam Hospital
state: Rhode Island
city: Greenville
country: United States
facility: Physicians East - Quadrangle
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Health Systems
state: Tennessee
city: Knoxville
country: United States
facility: Baptist Regional Cancer Center - Knoxville
state: Tennessee
city: Memphis
country: United States
facility: West Clinic
state: Tennessee
city: Memphis
country: United States
facility: Memphis Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, P.L.L.C.
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Lone Star Oncology
state: Texas
city: Dallas
country: United States
facility: Center for Oncology Research and Treatment, Medical City Hospital
state: Texas
city: San Antonio
country: United States
facility: Baptist Health System Cancer Program
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Charlottesville
country: United States
facility: Cancer Center at the University of Virginia
state: Virginia
city: Fredericksburg
country: United States
facility: Hematology-Oncology Associates of Frederiksburg, Inc.
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Advanced Health Care
state: Wisconsin
city: Wausau
country: United States
facility: UW Cancer Center Wausau Hospital
state: Wisconsin
city: Laramie
country: United States
facility: Irving Cancer Center
state: Wyoming
city: Porto Alegre
country: Brazil
facility: Porto Alegre Hospital
state: Rio Grande do Sul
city: Sorocaba
country: Brazil
facility: Instituto de Oncologia de Soracaba
state: Sao Paulo
city: Aracaiu-SE
country: Brazil
facility: Hospital Joao Alves Fiho
city: Belo Horizonte-MG
country: Brazil
facility: Hospital Socor
city: Curitiba-PR
country: Brazil
facility: Hospital Erastos Gaertner
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer
city: Rio de Janeiro
country: Brazil
facility: Oncologistas Associados
city: Sao Paulo
country: Brazil
facility: Hospital do Cancer A C Comargo
city: Calgary
country: Canada
facility: Tom Baker Cancer Center - Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Barrie
country: Canada
facility: Royal Victoria Hospital, Barrie
state: Ontario
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Sudbury
country: Canada
facility: Northeastern Ontario Regional Cancer Centre, Sudbury
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital - Toronto
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles Lemoyne
state: Quebec
city: Laval
country: Canada
facility: Cite de la Sante de Laval
state: Quebec
city: Levis
country: Canada
facility: L'Hotel Dieu de Levis
state: Quebec
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital - Montreal
state: Quebec
city: Montreal
country: Canada
facility: Hopital Du Sacre-Coeur de Montreal
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
city: Sainte Foy
country: Canada
facility: Centre Hospitalier de L'Universitaire de Quebec, Pavillon CHUL
state: Quebec
city: Ste-Foy
country: Canada
facility: L'Hopital Laval
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: St. Jerome Quebec
country: Canada
facility: Zoom International Incoporated
city: Ceske Budejovice
country: Czech Republic
facility: Centre of Clinical Oncology and Radiation Oncology
city: Hradec Kralove
country: Czech Republic
facility: Charles University Hospital
city: Prague
country: Czech Republic
facility: Onkologicka Klinka A Onkologicka Lab
city: Praha
country: Czech Republic
facility: Fakultni Nemocnice V Motole
city: Budapest
country: Hungary
facility: Semmelweis University
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Budapest
country: Hungary
facility: Fovarosi Onkormanyzat Szent Margit Korhaz, Okologia
city: Budapest
country: Hungary
facility: Szent Laszlo Korhaz
city: Budapest
country: Hungary
facility: Kozponti Honvedkorhaz I. Belgyogyaszat
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Onkologiai Tanzek
city: Gydr
country: Hungary
facility: Petz Aladar County Hospital
city: Gliwice
country: Poland
facility: Maria S. Curie Memorial Institute
city: Krakow (Cracow)
country: Poland
facility: Jagiellonian University
city: Lodz
country: Poland
facility: Institute of Oncology
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Onkologii Oddzial Chemioterapii
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Center
state: England
city: London
country: United Kingdom
facility: St. Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Guy's and St. Thomas' Hospitals NHS Trust
state: England
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital N.H.S. Trust
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: Daniel G. Haller, MD
role: STUDY_CHAIR
References:
citation: 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.