Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy With Trastuzumab in Treating Women With Metastatic Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	Other	EORTC-10995 EORTC-16999, IDBBC-EORTC-10995, NCT00036868

Objectives

1. 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®).
2. Compare the therapeutic activity of this regimen, in terms of objective response rate, in these patients.
3. Compare the duration of response and time to progression in patients treated with this regimen.
4. Compare the toxic effects of this regimen in these patients.

Entry 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

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/m²
• No prior cumulative dose of epirubicin more than 720 mg/m²
• No prior cumulative dose of mitoxantrone more than 90 mg/m²
• 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

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/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

Outcomes

Clinical heart failure rate measured by New York Heart Association classification, LVEF, and ECG
Response rate by RECIST

Duration of response by RECIST
Time to progression
Toxicity measured by CTC v2.0

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.

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.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Martine Piccart-Gebhart, MD, PhD, Study coordinator		Ph: 32-2-541-3206 Email: martine.piccart@bordet.be
Pierre Fumoleau, MD, PhD, Study coordinator		Ph: 33-3-8073-7506
Laura Biganzoli, MD, Study coordinator(Contact information may not be current)		Ph: 32-2-541-3501

Registry Information
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
Trial Start Date		2002-02-05
Registered in ClinicalTrials.gov		NCT00036868 1
Date Submitted to PDQ		2002-03-11
Information Last Verified		2006-01-05

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00036868