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Combination Chemotherapy With Trastuzumab in Treating Women With Metastatic Breast 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: NCT00036868
Recruitment Status : Unknown
Verified June 2013 by European Organisation for Research and Treatment of Cancer - EORTC.
Recruitment status was:  Active, not recruiting
First Posted : January 27, 2003
Last Update Posted : June 7, 2013
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary:

RATIONALE: Drugs used in chemotherapy such as cyclophosphamide, methotrexate, and fluorouracil 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. Combining chemotherapy with trastuzumab may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining combination chemotherapy with trastuzumab in treating women who have metastatic breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: trastuzumab Drug: CMF regimen Drug: cyclophosphamide Drug: fluorouracil Drug: methotrexate Phase 2

Detailed Description:


  • Compare the incidence of clinical heart failure in women with c-erbB2-positive metastatic breast cancer treated with cyclophosphamide, methotrexate, and fluorouracil in combination with trastuzumab (Herceptin®).
  • Compare the therapeutic activity of this regimen, in terms of objective response rate, in these patients.
  • Compare the duration of response and time to progression in patients treated with this regimen.
  • Compare the toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive CMF comprising cyclophosphamide orally on days 1-14 or IV on days 1 and 8 and methotrexate IV and fluorouracil IV on days 1 and 8. Patients also receive trastuzumab (Herceptin®) IV over 30-90 minutes once weekly beginning on day 1. Treatment repeats every 4 weeks for 8 courses. Patients then receive trastuzumab once every 3 weeks in the absence of disease progression, unacceptable toxicity, or patient refusal.

Patients are followed every 8 weeks until documentation of disease progression or initiation of a new anticancer therapy. Patients developing disease progression are followed every 12 weeks.

PROJECTED ACCRUAL: A total of 66 patients will be accrued for this study within 2 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study Of CMF Alone And In Combination With Anti c-erbB2 Antibody (Herceptin) In Women With c-erbB2 Positive Metastatic Breast Cancer
Study Start Date : February 2002
Actual Primary Completion Date : June 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: CMF + Herceptin Biological: trastuzumab
Drug: CMF regimen
Drug: cyclophosphamide
Drug: fluorouracil
Drug: methotrexate

Primary Outcome Measures :
  1. Clinical heart failure rate measured by New York Heart Association classification, LVEF, and ECG [ Time Frame: from registration ]
  2. Response rate by RECIST [ Time Frame: from registration ]

Secondary Outcome Measures :
  1. Duration of response by RECIST [ Time Frame: from registration ]
  2. Time to progression [ Time Frame: from registration ]
  3. Toxicity measured by CTC v2.0 [ Time Frame: from registration ]

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:   Female
Accepts Healthy Volunteers:   No


  • Histologically confirmed metastatic breast cancer c-erbB2 positive (3+ overexpression by the HercepTest™ method) in the primary tumor or metastatic site
  • At least 1 unidimensionally measurable target lesion

    • At least 20 mm by conventional techniques OR
    • At least 10 mm by spiral CT scan
    • Lesions that have been irradiated in the preceding 3 months cannot be used as target lesions unless they have appeared or clearly progressed since prior irradiation
    • No bone lesions as the only target lesions
  • No contralateral breast cancer that is c-erbB2-positive or c-erbB2-negative/unknown, with status determined on a metastatic site
  • No CNS metastases

    • CT scan of brain and CSF cytology are required if neurologic symptoms are present
  • Hormone receptor status:

    • Any estrogen or progesterone receptor status



  • 18 and over


  • Female

Menopausal status:

  • Any status

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified


  • Neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3


  • Bilirubin no greater than 1.25 times upper limit of normal (ULN)
  • Transaminases less than 2.5 times ULN (5 times ULN if liver metastases present)


  • For patients age 18 to 69:

    • Creatinine no greater than ULN
  • For patients age 70 and over:

    • Creatinine clearance normal


  • LVEF normal by MUGA or echocardiogram
  • No clinical heart failure


  • No malignancy-associated dyspnea at rest
  • No requirement for supportive oxygen therapy


  • Not pregnant or nursing
  • No other prior or concurrent malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or basal cell skin cancer
  • No psychological, familial, sociological, or geographical condition that would preclude compliance with study therapy and follow-up schedule


Biologic therapy:

  • No prior anti-c-erbB2 antibody, including trastuzumab (Herceptin®)
  • No other concurrent biologic therapy


  • No more than 1 prior chemotherapy regimen for metastatic breast cancer
  • Prior combination of cyclophosphamide, methotrexate, and fluorouracil (CMF) allowed in the adjuvant or metastatic setting only if the disease-free interval after completion of CMF was at least 12 months
  • Prior anthracyclines and/or taxanes allowed
  • At least 4 weeks since prior anthracyclines
  • No prior cumulative dose of doxorubicin more than 360 mg/m^2
  • No prior cumulative dose of epirubicin more than 720 mg/m^2
  • No prior cumulative dose of mitoxantrone more than 90 mg/m^2
  • No other concurrent chemotherapy

Endocrine therapy:

  • More than 2 weeks since prior hormonal therapy in the adjuvant or metastatic setting
  • No concurrent hormonal therapy


  • See Disease Characteristics
  • No concurrent radiotherapy


  • Not specified


  • No other concurrent anticancer therapy or investigational drugs
  • No concurrent bisphosphonates started after study enrollment except for hypercalcemia

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): NCT00036868

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Ziekenhuis Netwerk Antwerpen Middelheim
Antwerp, Belgium, 2020
Institut Jules Bordet
Brussels, Belgium, 1000
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
Herlev Hospital - University Hospital of Copenhagen
Copenhagen, Denmark, DK-2730
National Cancer Institute of Egypt
Cairo, Egypt
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, France, 21079
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands, 1091 HA
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
Nijmegen Cancer Center at Radboud University Medical Center
Nijmegen, Netherlands, NL-6500 HB
Medical University of Gdansk
Gdansk, Poland, 80-211
Institute of Oncology and Radiology of Serbia
Belgrade, Serbia, 11000
South Africa
Medical Oncology Centre of Rosebank
Johannesburg, South Africa, 2193
United Kingdom
Western Infirmary
Glasgow, Scotland, United Kingdom, G11 6NT
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
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Study Chair: David Cameron Western General Hospital, Edinburgh

Publications of Results:
Neskovic-Konstantinovic Z, Nooij M, Khaled H, et al.: Safety and efficacy of combined trastuzumab and CMF therapy in women with metastatic breast cancer: EORTC protocol 10995. [Abstract] J Clin Oncol 25 (Suppl 18): A-1040, 2007.

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC Identifier: NCT00036868    
Other Study ID Numbers: EORTC-10995-16999
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: June 7, 2013
Last Verified: June 2013
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage IV breast cancer
recurrent breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Antineoplastic Agents, Immunological