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Fluorouracil and Leucovorin Plus Either Irinotecan or Oxaliplatin With or Without Cetuximab in Treating Patients With Previously Untreated Metastatic Adenocarcinoma of the Colon or Rectum
This study is ongoing, but not recruiting participants.
First Received: February 10, 2004   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00077233
  Purpose

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, irinotecan, and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining more than one drug with a monoclonal antibody may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective with or without cetuximab in treating metastatic adenocarcinoma (cancer) of the colon or rectum.

PURPOSE: Randomized phase III trial to compare the effectiveness of combining fluorouracil and leucovorin with either irinotecan or oxaliplatin with or without cetuximab in treating patients who have metastatic cancer of the colon or rectum.


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

MedlinePlus related topics: Cancer Colorectal Cancer
Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Oxaliplatin Irinotecan U 101440E Irinotecan hydrochloride Cetuximab Leucovorin Calcium Folinic acid calcium salt pentahydrate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control
Official Title: A Phase III Trial Of Irinotecan /5-FU/ Leucovorin Or Oxaliplatin /5-FU / Leucovorin With And Without Cetuximab (C225) For Patients With Untreated Metastatic Adenocarcinoma Of The Colon or Rectum

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

Study Start Date: January 2004
Detailed Description:

OBJECTIVES:

Primary

  • Compare the survival rate of patients with previously untreated metastatic adenocarcinoma of the colon or rectum treated with fluorouracil and leucovorin calcium with oxaliplatin or irinotecan and with or without cetuximab.

Secondary

  • Determine the level of epidermal growth factor receptor (EGFR) expression in patients treated with these regimens.
  • Determine whether expression of EGFR activity, markers of EGFR activity, and serum levels of insulin-like growth factor-1, C-peptide, and insulin-like growth factor binding protein 3 are independent predictors of response rate, time to tumor progression, and survival of patients treated with these regimens.
  • Correlate specific germline polymorphisms related to chemotherapy metabolism and resistance with treatment-related toxicity, tumor response, time to tumor progression, and survival of patients treated with these regimens.
  • Correlate expression of putative prognostic markers in the tumor with tumor response, time to tumor progression, and survival of patients treated with these regimens.
  • Correlate diet, obesity, physical activity, and other lifestyle habits with treatment-related toxicity, progression-free survival, and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to prior adjuvant therapy (yes vs no) and prior pelvic radiotherapy (yes vs no). Patients are randomized to 1 of 4 treatment arms.

  • Arm I (FOLFIRI): Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours on days 1, 15, 29, and 43 and fluorouracil IV continuously over 46-48 hours beginning on days 1, 15, 29, and 43.
  • Arm II (FOLFIRI and cetuximab): Patients receive FOLFIRI as in arm I and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50.
  • Arm III (FOLFOX): Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on days 1, 15, 29, and 43 and fluorouracil IV continuously over 46-48 hours beginning on days 1, 15, 29, and 43.
  • Arm IV (FOLFOX and cetuximab): Patients receive FOLFOX as in arm III and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50.

In all arms, courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 2 years and then every 3 months for 3 years.

PROJECTED ACCRUAL: Approximately 2,200 patients (550 per treatment arm) will be accrued for this study within 4.6 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 metastatic colorectal adenocarcinoma

    • Primary site of disease in the large bowel as determined endoscopically, surgically, or radiologically
    • Histologic or cytologic confirmation is not required for recurrent metastatic disease in patients with prior colorectal cancer treated with surgery unless either of the following criteria are met:

      • More than 5 years have elapsed between the prior primary surgery and the development of metastatic disease
      • Primary cancer was stage I
  • Tumor tissue available for epidermal growth factor receptor (EGFR) status analysis
  • No pleural effusion or ascites that causes grade 2 or greater dyspnea
  • No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Granulocyte count ≥ 1,500/mm^3
  • Hemoglobin ≥ 9.0 g/dL (transfusion allowed)
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Bilirubin ≤ 1.5 mg/dL
  • AST ≤ 5.0 times upper limit of normal (ULN)
  • Albumin ≥ 2.5 g/dL
  • No evidence of Gilbert's syndrome

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

  • No unstable angina
  • No congestive heart failure
  • No prior myocardial infarction
  • No prior stroke
  • No other significant cardiac disease
  • LVEF ≥ normal by echocardiogram or MUGA

Pulmonary

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

Neurologic

  • No uncontrolled seizure disorder
  • No Temporarily closed neurological disease
  • No symptomatic sensory peripheral neuropathy grade 2 or greater

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No predisposing uncontrolled colonic or small bowel disorder as evidenced by > 3 watery or soft stools daily at baseline*
  • No known sensitivity to chimerized or murine antibodies, cetuximab or other EGFR inhibitors, or tyrosine kinase inhibitors
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix NOTE: *In patients without a colostomy or ileostomy; patients with a colostomy or ileostomy are eligible at the discretion of the investigator

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior biologic therapy for metastatic colorectal cancer
  • No prior chimerized or murine antibodies
  • No prior cetuximab
  • No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

  • See Radiotherapy
  • More than 12 months since prior chemotherapy
  • No prior chemotherapy for metastatic colorectal cancer
  • No prior irinotecan or oxaliplatin in the adjuvant or metastatic setting
  • No more than 6 months or 4 courses of prior adjuvant chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • No prior endocrine therapy for metastatic colorectal cancer
  • No concurrent hormonal therapy except the following:

    • Steroids for adrenal failure
    • Hormones administered for non-disease-related conditions (e.g., insulin for diabetes)
    • Intermittent use of dexamethasone as an antiemetic

Radiotherapy

  • More than 4 weeks since prior radiotherapy
  • No prior radiotherapy for metastatic colorectal cancer
  • No prior radiotherapy to more than 25% of bone marrow
  • Prior standard adjuvant chemoradiotherapy for rectal cancer allowed
  • Prior adjuvant radiotherapy with radiosensitizing chemotherapy allowed
  • No concurrent palliative radiotherapy except whole brain radiotherapy for documented CNS disease

Surgery

  • See Disease Characteristics
  • More than 4 weeks since prior major surgery*
  • More than 2 weeks since prior minor surgery* and recovered
  • No prior surgery for metastatic colorectal cancer NOTE: *Insertion of a vascular device is not considered major or minor surgery

Other

  • At least 4 weeks since prior itraconazole or ketoconazole
  • No other prior treatment for metastatic colorectal cancer
  • No prior EGFR inhibitors
  • No prior tyrosine kinase inhibitors
  • No other concurrent investigational agents
  • No concurrent agents to minimize neurotoxicity of oxaliplatin (e.g., carbamazepine, magnesium, or calcium)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00077233

  Show 77 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Alan P. Venook, MD UCSF Helen Diller Family Comprehensive Cancer Center
Investigator: Charles S. Fuchs, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
Venook A, Niedzwiecki D, Hollis D, et al.: Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX) ± cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results. [Abstract] J Clin Oncol 24 (Suppl 18): A-3509, 2006.

Study ID Numbers: CDR0000350016, CALGB-80203
Study First Received: February 10, 2004
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00077233     History of Changes
Health Authority: United States: Federal Government

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

Study placed in the following topic categories:
Antimetabolites
Immunologic Factors
Gastrointestinal Diseases
Rectal Neoplasms
Colonic Diseases
Irinotecan
Leucovorin
Rectal Diseases
Oxaliplatin
Vitamins
Micronutrients
Vitamin B Complex
Digestive System Neoplasms
Cetuximab
Rectal Neoplasm
Trace Elements
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Recurrence
Camptothecin
Carcinoma
Calcium, Dietary
Digestive System Diseases
Rectal Cancer
Fluorouracil
Gastrointestinal Neoplasms
Adenocarcinoma
Antineoplastic Agents, Phytogenic
Colonic Neoplasms

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

ClinicalTrials.gov processed this record on May 07, 2009