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Erlotinib and Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00049101
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : June 24, 2013
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining erlotinib with combination chemotherapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining erlotinib with oxaliplatin, leucovorin, and fluorouracil in treating patients who have metastatic colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: erlotinib hydrochloride Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Phase 1 Phase 2

Detailed Description:


  • Determine the maximum tolerated dose of erlotinib when administered with oxaliplatin, leucovorin calcium, and fluorouracil in patients with metastatic colorectal cancer.
  • Determine the pharmacokinetics of this regimen in these patients.
  • Determine any antitumor activity of this regimen in these patients.
  • Determine the time to progression in patients treated with this regimen.
  • Determine the objective response rate and response duration in patients treated with this regimen.
  • Determine the safety and tolerability of this regimen in these patients.

OUTLINE: This is a dose-escalation study of erlotinib.

  • Phase I: During the first week of the first course only, patients receive oral erlotinib daily alone. Patients then begin the regular schedule comprising oral erlotinib daily, oxaliplatin IV over 2 hours on day 1, and leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1 and 2. Treatment repeats every 2 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive erlotinib at the MTD plus oxaliplatin, leucovorin calcium, and fluorouracil as in phase I. Erlotinib may be administered alone if toxicity is caused by oxaliplatin, leucovorin calcium, and fluorouracil.

Patients are followed for at least 6 months or until disease progression.

PROJECTED ACCRUAL: A total of 4-18 patients will be accrued for phase I of this study within 1-4 months. A total of 50 patients will be accrued for phase II of this study within 10 months.

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Study Type : Interventional  (Clinical Trial)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study Of OSI-774 In Combination With Oxaliplatin, And 5-Fluourouracil In Patients With Metastatic Colorectal Carcinoma
Study Start Date : August 2002
Actual Study Completion Date : August 2004

Resource links provided by the National Library of Medicine

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed colon or rectal cancer

    • Metastatic or unresectable disease
  • Unidimensionally measurable disease required for phase II only

    • At least 20 mm by x-ray, CT scan, MRI, or photography
    • The following are not considered measurable:

      • Pleural effusion or ascites
      • Osteoblastic lesions
      • Evidence of disease on bone scan alone
      • Progressive irradiated lesions alone
      • Bone marrow involvement
      • Brain metastases
      • Malignant hepatomegaly by physical exam alone
      • Chemical markers (e.g., carcinoembryonic antigen)
    • Recurrent disease after surgery or radiotherapy is considered measurable as long as the following criteria are met:

      • At least 4 weeks since prior surgery or radiotherapy
      • Measurable disease exists outside the radiation port or clear progression exists within the radiation port
  • Tissue accessible for immunohistochemical evidence of epidermal growth factor receptor expression from a metastatic site (phase II only)
  • No known brain metastases



  • 18 and over

Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • More than 3 months


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


  • Bilirubin normal
  • AST/ALT no greater than 2.5 times upper limit of normal


  • Creatinine normal OR
  • Creatinine clearance at least 60 mL/min


  • No unstable angina pectoris
  • No symptomatic congestive heart failure
  • No cardiac arrhythmia
  • No uncontrolled hypertension (systolic blood pressure greater than 150 mm Hg)


  • No abnormalities of the cornea (e.g., severe dry eye syndrome or Sjogren's syndrome)
  • No congenital abnormality (e.g., Fuch's dystrophy)
  • No abnormal slit-lamp examination using vital dye (e.g., fluorescein or Bengal-Rose)
  • No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear-production test)
  • Mild dry eye syndrome allowed if patient can use artificial tears and ophthalmologist concurs


  • No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
  • No active peptic ulcer disease


  • Must be able and willing to undergo a mediport insertion
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except previously excised and inactive basal cell or squamous cell skin cancer
  • No prior allergic reactions attributed to compounds of similar chemical or biological composition to erlotinib or other study drugs (e.g., epidermal growth factor inhibitors like cetuximab)
  • No significant traumatic injury within the past 3 weeks
  • No peripheral neuropathy grade 2 or greater
  • No ongoing or active infection
  • No other uncontrolled concurrent illness that would preclude study entry
  • No psychiatric illness or social situation that would preclude study compliance


Biologic therapy

  • Not specified


  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • Phase I:

    • Prior chemotherapy allowed
  • Phase II:

    • No prior chemotherapy for metastatic disease
    • Prior adjuvant therapy allowed if disease progresses during adjuvant therapy
    • No prior oxaliplatin

Endocrine therapy

  • Not specified


  • See Disease Characteristics
  • More than 4 weeks since prior radiotherapy and recovered


  • See Disease Characteristics
  • More than 3 weeks since prior major surgery and recovered
  • No prior surgical procedures affecting absorption


  • No other concurrent investigational agents
  • No other concurrent anticancer agents or therapies (commercial or investigational)
  • No concurrent combination antiretroviral therapy for HIV-positive patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00049101

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United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
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Study Chair: Leonard B. Saltz, MD Memorial Sloan Kettering Cancer Center
Layout table for additonal information Identifier: NCT00049101    
Other Study ID Numbers: CDR0000257808
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: June 24, 2013
Last Verified: April 2004
Keywords provided by National Cancer Institute (NCI):
recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Erlotinib Hydrochloride
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Protective Agents
Vitamin B Complex