Combination Chemotherapy With Trastuzumab in Treating Women With Metastatic Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00036868
First received: May 13, 2002
Last updated: June 6, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Breast Cancer
Biological: trastuzumab
Drug: CMF regimen
Drug: cyclophosphamide
Drug: fluorouracil
Drug: methotrexate
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Clinical heart failure rate measured by New York Heart Association classification, LVEF, and ECG [ Time Frame: from registration ] [ Designated as safety issue: No ]
  • Response rate by RECIST [ Time Frame: from registration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of response by RECIST [ Time Frame: from registration ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: from registration ] [ Designated as safety issue: No ]
  • Toxicity measured by CTC v2.0 [ Time Frame: from registration ] [ Designated as safety issue: Yes ]

Enrollment: 90
Study Start Date: February 2002
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CMF + Herceptin Biological: trastuzumab Drug: CMF regimen Drug: cyclophosphamide Drug: fluorouracil Drug: methotrexate

Detailed Description:

OBJECTIVES:

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Sex:

  • Female

Menopausal status:

  • Any status

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

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

Hepatic:

  • 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)

Renal:

  • For patients age 18 to 69:

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

    • Creatinine clearance normal

Cardiovascular:

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

Pulmonary:

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

Other:

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

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

Chemotherapy:

  • 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

Radiotherapy:

  • See Disease Characteristics
  • No concurrent radiotherapy

Surgery:

  • Not specified

Other:

  • No other concurrent anticancer therapy or investigational drugs
  • No concurrent bisphosphonates started after study enrollment except for hypercalcemia
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00036868

Locations
Belgium
Ziekenhuis Netwerk Antwerpen Middelheim
Antwerp, Belgium, 2020
Institut Jules Bordet
Brussels, Belgium, 1000
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
Denmark
Herlev Hospital - University Hospital of Copenhagen
Copenhagen, Denmark, DK-2730
Egypt
National Cancer Institute of Egypt
Cairo, Egypt
France
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, France, 21079
Netherlands
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
Poland
Medical University of Gdansk
Gdansk, Poland, 80-211
Serbia
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
Investigators
Study Chair: David Cameron Western General Hospital, Edinburgh
  More Information

Additional Information:
Publications:
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.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00036868     History of Changes
Other Study ID Numbers: EORTC-10995-16999, EORTC-10995, EORTC-16999, IDBBC-EORTC-10995
Study First Received: May 13, 2002
Last Updated: June 6, 2013
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Methotrexate
Trastuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites
Antimetabolites, Antineoplastic
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014