This trial is active, not recruiting.

Condition breast cancer
Treatments fac, paclitaxel
Phase phase 3
Sponsor Spanish Breast Cancer Research Group
Collaborator Bristol-Myers Squibb
Start date September 2003
End date December 2013
Trial size 1929 participants
Trial identifier NCT00129389, GEICAM 2003-02


This is a prospective, open-label, randomized, phase III trial. Patients will be stratified after breast surgery, as per investigational site; menopausal status; node negative diagnosis, as per sentinel-node technique versus lymphadenectomy; hormone receptor status (positive versus negative). Patients will be randomized to:

- FAC x 6 (cycles): 5-fluorouracil 500 mg/m2 + doxorubicin 50 mg/m2 + cyclophosphamide 500 mg/m2 day 1, every 3 weeks, for 6 cycles.

- FAC x 4 (cycles) → Taxol® x 8 (cycles): 5-fluorouracil 500 mg/m2 + doxorubicin 50 mg/m2 + cyclophosphamide 500 mg/m2 day 1, every 3 weeks, for 4 cycles, followed by 8 administrations of weekly paclitaxel 100 mg/m2

Premenopausal women with hormone receptor positive tumors must receive tamoxifen 20 mg daily for 5 years, after the end of chemotherapy.

Postmenopausal women with hormone receptor positive tumors are allowed to receive aromatase inhibitors as initial adjuvant hormone therapy or after tamoxifen.

All patients with breast conservative surgery must receive radiotherapy.

Estimated 5-year disease-free survival in the control arm (FAC x 6) is expected to be 80%. It is expected that disease-free survival will increase by 5% in the experimental arm (FAC-paclitaxel). 906 patients per arm must be recruited, to detect this difference with an alpha error of 0.05 and 80% power. Assuming a 6% post-randomization drop-out rate, 960 patients per arm are needed, 1920 in total.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
(Active Comparator)
FAC x 6: 5-fluorouracil 500 mg/m2 i.v. + doxorubicin 50 mg/m2 i.v. + cyclophosphamide 500 mg/m2 i.v. every 3 weeks, for 6 cycles.
FAC X 4 + 8 Taxol
FAC x 4 -> Taxol x 8: 5-fluorouracil 500 mg/m2 i.v. + doxorubicin 50 mg/m2 i.v. + cyclophosphamide 500 mg/m2 i.v. every 3 weeks, for 4 cycles followed by weekly Taxol 100 mg/ m2 for 8 cycles (days 1, 8, 15, 22, 29, 36, 43 y 50).

Primary Outcomes

Disease-free survival
time frame: 5 years

Secondary Outcomes

Overall survival
time frame: 5 years
time frame: During and after chemotherapy completion

Eligibility Criteria

Female participants from 18 years up to 70 years old.

Inclusion Criteria: - Written informed consent. - Histological diagnoses of operable invasive adenocarcinoma of the breast (T1-T3). Tumors must be HER2 negative. Patients must be free of disease in the axilla (node negative). If lymphadenectomy is done, at least 10 nodes must be examined. If sentinel node technique is used, sentinel node must be free of disease. Patients must present at least one high risk criterion (St. Gallen, 1998) as follows: - Tumor size > 2 cm; and/or - ER and PgR negative; and/or - Histological grade 2-3; and/or - Age < 35 years old. - Time window between surgery and study randomization must be less than 60 days. - Surgery must consist of mastectomy or conservative surgery. Margins free of disease and ductal carcinoma in situ (DCIS) are required. Lobular carcinoma is not considered a positive margin. - Patients must not present evidence of metastatic disease. - Status of hormone receptors in primary tumor. Results must be available before the end of adjuvant chemotherapy. - Status of HER2 in primary tumor, known before randomization. Patients with immune histochemistry (IHC) 0 or +1 are eligible. For patients with ICH 2+, fluorescent in situ hybridization (FISH) is mandatory and result must be negative. - Age >= 18 and <= 70 years old. - Performance status (Karnofsky index) >= 80. - Normal electrocardiogram (EKG) in the 12 weeks prior to randomization. If needed, normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF). - Laboratory results (within 14 days prior to randomization): - Hematology: neutrophils >= 1.5 x 10^9/l; platelets >= 100x 10^9/l; hemoglobin >= 10 mg/dl; - Hepatic function: total bilirubin <= 1 upper normal limit (UNL); SGOT and SGPT <= 2.5 UNL; alkaline phosphatase <= 2.5 UNL. If values of SGOT and SGPT > 1.5 UNL are associated with alkaline phosphatase > 2.5 UNL, patient is not eligible. - Renal function: creatinine <= 175 mmol/l (2 mg/dl); creatinine clearance >= 60 ml/min. - Complete stage workup during the 12 weeks prior to randomization (mammograms are allowed within a 20 week time window). All patients must have a bilateral mammogram, thorax x-ray, abdominal echography and/or computed tomography (CT)-scan. If bone pain, and/or alkaline phosphatase elevation, a bone scintigraphy is mandatory. This test is recommended for all patients. Other tests, as clinically indicated. - Patients able to comply with treatment and study follow-up. - Negative pregnancy test done in the 14 previous days to randomization. Exclusion Criteria: - Prior systemic therapy for breast cancer. - Prior therapy with anthracyclines or taxanes (paclitaxel or docetaxel) for any malignancy. - Prior radiotherapy for breast cancer. - Bilateral invasive breast cancer. - Pregnant or lactating women. Adequate contraceptive methods must be used during chemotherapy and hormone therapy treatments. Negative pregnancy test in the 14 previous days to randomization. - Any T4 or N1-3 or M1 tumor. - HER2 positive breast cancer (IHC 3+ or positive FISH result). - Pre-existing grade >=2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria [NCI CTC] v-2.0). - Any other serious medical pathology, such as congestive heart failure, unstable angina, history of myocardial infarction during the previous year, uncontrolled HA or high risk arrhythmias. - History of neurological or psychiatric disorders, which could preclude the patients to free informed consent. - Active uncontrolled infection. - Active peptic ulcer; unstable diabetes mellitus. - Previous or current history of neoplasms different from breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumor curatively treated and without recurrence in the last 10 years; ductal in situ carcinoma in the same breast; lobular in situ carcinoma. - Concomitant treatment with other investigational products. Participation in other clinical trials with a non-marketed drug in the 20 previous days before randomization. - Concomitant treatment with other therapy for cancer. - Males.

Additional Information

Official title Multicenter Randomized Phase III Clinical Trial to Compare 6 FAC Cycles(Fluorouracil, Doxorubicin, Cyclophosphamide) vs. 4 FAC Cycles Followed by 8 Weekly Paclitaxel Administrations, as Adjuvant Treatment for Node Negative Operable Breast Cancer Patients
Trial information was received from ClinicalTrials.gov and was last updated in November 2012.
Information provided to ClinicalTrials.gov by Spanish Breast Cancer Research Group.