Working… Menu
Help guide our efforts to modernize
Send us your comments by March 14, 2020.

Combination Chemotherapy Plus Trastuzumab in Treating Patients With Advanced, Recurrent, or 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: NCT00006015
Recruitment Status : Terminated (lack of sufficient accrual)
First Posted : January 27, 2003
Last Update Posted : May 3, 2013
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. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: This phase II trial is studying combination chemotherapy plus trastuzumab to see how well it works in treating patients with advanced, recurrent, or metastatic colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Biological: trastuzumab Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Phase 2

Detailed Description:


  • Determine the response rate of patients who overexpress HER-2/neu with metastatic colorectal adenocarcinoma who have progressed on at least 1 prior, but no more than 2 prior, chemotherapy regimens for metastatic colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin, and trastuzumab (Herceptin).
  • Determine the time to progression of these patients treated with this regimen.
  • Determine the overall toxicity of this regimen in these patients.

OUTLINE: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22, followed by oxaliplatin IV over 2 hours on days 1 and 15, and then followed by leucovorin calcium IV over 2 hours on days 1, 8, and 15. Fluorouracil IV is administered at the midpoint of the leucovorin calcium infusion on days 1, 8, and 15. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression.

PROJECTED ACCRUAL: A total of 20-45 patients will be accrued for this study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study Evaluating the Combination of 5-Fluorouracil, Leucovorin, Oxaliplatin, and Herceptin in the Treatment of Patients With Metastatic Colorectal Cancer Who Have Progressed After 5-FU and/or Irinotecan-Containing Therapy
Study Start Date : May 2000
Actual Primary Completion Date : December 2002
Actual Study Completion Date : February 2003

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Combination Chemotx
Combination chemotherapy for metastatic colorectal cancer in patients who have disease progression after 5-FU and/or irinotecan-containing therapy
Biological: trastuzumab
4 mg/kg IV infusion Day 1, then weekly 2 mg/kg IV infusion (on Days 8, 15, & 22)
Other Name: Herceptin

Drug: fluorouracil
500 mg/sq m IV push weekly for 3 weeks, followed by a 1 wk break
Other Name: 5-FU

Drug: leucovorin calcium
500 mg/sq m IV infusion over 2 hours weekly for 3 weeks, then a 1 wk break

Drug: oxaliplatin
85 mg/sq m IV infusion over 2 hours Days 1 & 15 of each cycle

Primary Outcome Measures :
  1. Response rate [ Time Frame: Every 2 tx cycles ]
  2. Time to progression [ Time Frame: Every 2 tx cycles ]
  3. Overall toxicity [ Time Frame: Each cycle during tx ]

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.

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


  • Histologically confirmed advanced, recurrent, or metastatic colorectal adenocarcinoma
  • Resected CNS metastases stable greater than 1 month after completion of radiotherapy for CNS metastases eligible

    • No existing CNS metastases allowed
  • Measurable disease

    • At least 1 dimension as at least 20 mm with conventional techniques OR
    • At least 10 mm with spiral CT scan
    • No truly nonmeasurable lesions:

      • Bone lesions
      • Leptomeningeal disease
      • Lymphangitis cutis/pulmonis
      • Abdominal masses not confirmed and followed by imaging techniques
      • Cystic lesions
  • Must have progressed on at least 1 prior, but no more than 2 prior, fluorouracil and/or irinotecan containing treatment regimens for metastatic colorectal cancer
  • Must have documented HER-2/neu overexpression by immunohistochemistry staining

    • Staining score at least 2+



  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified


  • Granulocyte count at least 1,500/mm3
  • Platelet count at least 100,000/mm3


  • Bilirubin no greater than 2.0 mg/dL
  • AST no greater than 2.5 times upper limit of normal


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


  • No history of cardiac ischemia or congestive heart failure
  • LVEF at least 50% by ECG or MUGA


  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No concurrent second malignancy except nonmelanoma skin cancers or carcinoma in situ of the cervix unless completed therapy and considered to be at less than 30% risk of relapse


Biologic therapy:

  • Not specified


  • See Disease Characteristics
  • No prior platinum containing chemotherapy
  • At least 3 weeks since prior chemotherapy and recovered
  • No other concurrent chemotherapy

Endocrine therapy:

  • Not specified


  • At least 3 weeks since prior radiotherapy and recovered


  • Not specified

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): NCT00006015

Show Show 47 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Layout table for investigator information
Study Chair: Jeffrey W. Clark, MD Massachusetts General Hospital

Publications of Results:
Clark JW, Niedzwiecki D, Hollis D, et al.: Phase II trial of 5-fluororuacil (5-FU), leucovorin (LV), oxaliplatin (Ox), and trastuzamab (T) for patients with metastatic colorectal cancer (CRC) refractory to initial therapy. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-3584, 2003.

Layout table for additonal information
Responsible Party: Monica M Bertagnolli, Cancer and Leukemia Group B Identifier: NCT00006015    
Other Study ID Numbers: CDR0000068024
U10CA031946 ( U.S. NIH Grant/Contract )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: May 3, 2013
Last Verified: June 2011
Keywords provided by National Cancer Institute (NCI):
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Colonic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Physiological Effects of Drugs
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors