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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

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

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


- 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

- 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

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

Inclusion Criteria


- 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

- 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

- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

from registration

Safety Issue:


Principal Investigator

David Cameron

Investigator Role:

Study Chair

Investigator Affiliation:

Western General Hospital, Edinburgh


United States: Federal Government

Study ID:




Start Date:

February 2002

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms