A multi-center, open-label, single-arm Phase II trial assessing the efficacy and safety of
weekly bolus infusions of 5-fluorouracil combined with CoFactor (5-10
methylenetetrahydrofolate) in advanced breast cancer patients who failed anthracycline and
taxane chemotherapy regimens.
Inclusion Criteria:
- Signed informed consent.
- Women with a histologically/cytologically proven diagnosis of advanced adenocarcinoma
of the breast.
- Measurable disease. At least one unidimensionally measurable non-bony lesion with a
diameter >=10 mm using spiral CT scans (use of spiral CT must be documented in medical
records and used consistently throughout the study) or >= 20 mm using conventional CT
or MRI scans outside the irradiated area according to RECIST criteria.
- Patients having failed both prior anthracycline and taxane derivative chemotherapy
regimens. Anthrocycline and Taxane failure definitions as defined in the protocol.
- No more than two prior chemotherapy regimens for advanced disease.
- Performance status (ECOG) <= 2 or Karnofsky >= 70
- Age >= 18 years.
- Life expectancy >= 12 weeks.
- Adequate organ function as shown by the following:
1. WBCs >= 3. 0 x 109/L, absolute neutrophil count (ANC)>= 1. 5 x 109/L, platelets >=
100 x 109/L, hemoglobin >= 9 g/dL
2. Bilirubin <= 1. 25 x the upper limit of normal (ULN),aspartate
aminotransferase(AST or alanine aminotransferase(ALT),= 3 x ULN (or <= 5 x ULN in
case of liver metastases)
3. Serum calcium within normal limits
4. Serum albumin within the normal range for the study site
5. Creatinine clearance >= 60 mL/min (Cockroft and Gault)
6. Left ventricular ejection fraction (LVEF) within normal limits as shown by
echocardiography or scintigraphy (multiple-gated acquisition scan).
- Patients of childbearing potential must be using medically acceptable contraception
for 4 weeks before start of study treatment and 4 months after study treatment
completion. Patients of childbearing potential must have a negative pregnancy test
result within 7 days prior to study treatment initiation.
- Patients with parenchymal brain metastases must be either adequately controlled
following resection or completed appropriate radiation therapy and be receiving a
stable corticosteroid dose prior to study entry. Patients with leptomeningeal
involvement should not be included in the study.
Exclusion Criteria:
- Her2/neu positive tumor (2+ or 3+).
- Pregnancy or lactation
- Systemic cytotoxic anti-cancer therapy within <=4 weeks of study entry, or 6 weeks if
the systemic therapy contains a nitrosourea or mitomycin C. Hormonal anti-cancer
treatment must be ongoing, or must have been discontinued >3 months before study
entry.
- Prior 5-FU- and/or capecitabine-based palliative chemotherapy.
- Extensive prior radiotherapy affecting more than 30% of bone marrow reserves, or
bone marrow / stem cell transplantation.
- Participation in clinical studies of non-approved experimental agents or procedures
within <=4 weeks of study entry.
- History of other malignancy, unless cured and the patient has been disease-free for
>=2 years. Patients with a history of cervical carcinoma in situ or cured stage I
cervical cancer, or of epidermal or basal cell skin cancer, may be eligible for
enrollment after discussion with the sponsor.
- Previous unexpected reaction to fluoropyrimidines, with or without documented
deficiency of dihydropyrimidine dehydrogenase, or known hypersensitivity to 5-FU.
- Psychologic, familial, sociologic or geographic conditions which do not permit
compliance with the study protocol and/or study.
- Significant cardiac disease, including symptomatic ventricular arrhythmia, congestive
heart failure, myocardial infarction within 12 months before study entry.
- Concomitant treatment with any experimental drug or anti-cancer drug, except hormone
therapy or bisphosphonates.
