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Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer
This study has been completed.
First Received: April 6, 2000   Last Updated: October 15, 2009   History of Changes
Sponsor: North Central Cancer Treatment Group
Collaborators: National Cancer Institute (NCI)
Southwest Oncology Group
Eastern Cooperative Oncology Group
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005036
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective for colorectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of irinotecan with that of combination chemotherapy in treating patients who have advanced colorectal cancer that has not responded to previous treatment.


Condition Intervention Phase
Colorectal Cancer
Drug: FOLFOX regimen
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: oxaliplatin
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: A Randomized Phase III Equivalence Trial of Irinotecan (CPT-11) Versus Oxaliplatin (OXAL)/5-Fluorouracil (5-FU)/Leucovorin (CF) in Patients With Advanced Colorectal Carcinoma Previously Treated With 5-FU

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: November 1999
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Compare the overall survival of patients with locally advanced, locally recurrent, or metastatic colorectal cancer treated with oxaliplatin, fluorouracil, and leucovorin calcium versus irinotecan, after initial therapy with fluorouracil.
  • Determine the time to progression, time to treatment failure, and overall response rate in patients treated with these 2 regimens.
  • Determine the toxic effects of these 2 regimens in these patients.
  • Compare the quality of life of patients treated with these 2 regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (ECOG 0-1 vs 2), primary indicator lesion (hepatic vs pulmonary vs other), age (less than 65 vs at least 65 years), alkaline phosphatase (less than 2 vs at least 2 times ULN), fluorouracil failure (adjuvant vs metastatic), and membership (intergroup vs expanded participation project).

Patients are randomized to one of two treatment arms:

  • Arm I: Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on days 1 and 2, and fluorouracil IV bolus followed by IV infusion over 22 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Patients who experience progression or toxicity on the initial regimen may crossover to the other regimen. At least 3 weeks must elapse between regimens.

Quality of life is assessed at baseline, prior to each chemotherapy course, at crossover, and at the end of the study.

Patients are followed every 6 months for 3 years or until death.

PROJECTED ACCRUAL: A total of 560 patients will be accrued for this study within 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed locally advanced, locally recurrent, or metastatic colorectal adenocarcinoma not curable by surgery or radiotherapy
  • Progressive disease following:

    • One prior fluorouracil based chemotherapy regimen for metastatic disease OR
    • Failure during or within 6 months after fluorouracil based adjuvant therapy
  • Measurable or evaluable disease
  • No CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 12 weeks

Hematopoietic:

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 9 g/dL (transfusion allowed)

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • AST no greater than 5 times upper limit of normal (ULN)
  • Alkaline phosphatase no greater than 5 times ULN

Renal:

  • Creatinine no greater than 1.5 times ULN

Cardiovascular:

  • No uncontrolled high blood pressure
  • No unstable angina
  • No symptomatic congestive heart failure
  • No myocardial infarction with the past 6 months
  • No serious uncontrolled cardiac arrhythmias
  • No New York Heart Association class III or IV heart disease

Pulmonary:

  • No pleural effusion or ascites that cause respiratory compromise (e.g., dyspnea grade 2 or greater)
  • No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Fluent in English
  • No active or uncontrolled infection
  • No other prior malignancy within the past 5 years, except:
  • Adequately treated basal or squamous cell skin cancer
  • Adequately treated noninvasive carcinomas
  • No sensory neuropathy grade 2 or greater
  • No uncontrolled colonic or small bowel disorders (greater than 3 loose stools daily)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No concurrent sargramostim (GM-CSF)

Chemotherapy:

  • At least 4 weeks since prior chemotherapy and recovered
  • No more than 1 prior chemotherapy regimen for advanced colorectal cancer
  • No prior irinotecan or other camptothecin derivative (e.g., topotecan)
  • No prior oxaliplatin
  • No other concurrent investigational chemotherapy agents

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 4 weeks since prior major radiotherapy
  • No prior radiotherapy to greater than 25% of bone marrow

Surgery:

  • At least 4 weeks since prior major surgery and recovered
  • At least 2 weeks since prior minor surgery and recovered
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005036

  Show 127 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Southwest Oncology Group
Eastern Cooperative Oncology Group
Investigators
Study Chair: Henry C. Pitot, MD Mayo Clinic
Study Chair: Philip A. Philip, MD, PhD, FRCP Barbara Ann Karmanos Cancer Institute
Study Chair: Edith P. Mitchell, MD, FACP Kimmel Cancer Center (KCC)
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000067623, NCCTG-N9841, ECOG-N9841, SWOG-N9841
Study First Received: April 6, 2000
Last Updated: October 15, 2009
ClinicalTrials.gov Identifier: NCT00005036     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage III colon cancer
stage IV colon cancer
stage III rectal cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gastrointestinal Diseases
Antineoplastic Agents
Colonic Diseases
Irinotecan
Physiological Effects of Drugs
Leucovorin
Rectal Diseases
Oxaliplatin
Neoplasms by Site
Vitamins
Therapeutic Uses
Micronutrients
Vitamin B Complex
Digestive System Neoplasms
Growth Substances
Enzyme Inhibitors
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Camptothecin
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on November 27, 2009