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)

July 5, 2000
January 27, 2003
May 3, 2013
May 2000
December 2002   (Final data collection date for primary outcome measure)
  • Response rate [ Time Frame: Every 2 tx cycles ]
  • Time to progression [ Time Frame: Every 2 tx cycles ]
  • Overall toxicity [ Time Frame: Each cycle during tx ]
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Complete list of historical versions of study NCT00006015 on Archive Site
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Combination Chemotherapy Plus Trastuzumab in Treating Patients With Advanced, Recurrent, or Metastatic Colorectal Cancer
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

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.


  • 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.

Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Colorectal Cancer
  • 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
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
  • Drug: fluorouracil
  • Drug: leucovorin calcium
  • Drug: oxaliplatin
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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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February 2003
December 2002   (Final data collection date for primary outcome measure)


  • 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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
U10CA031946 ( U.S. NIH Grant/Contract )
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Monica M Bertagnolli, Cancer and Leukemia Group B
National Cancer Institute (NCI)
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Study Chair: Jeffrey W. Clark, MD Massachusetts General Hospital
National Cancer Institute (NCI)
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP