Fluorouracil Plus Doxorubicin and Cyclophosphamide (FAC) Versus FAC Plus Weekly Paclitaxel as Adjuvant Treatment of Node Negative High Risk Breast Cancer Patients
Information source: Spanish Breast Cancer Research Group
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Breast Cancer
Intervention: paclitaxel (Drug)
Phase: Phase 3
Sponsored by: Spanish Breast Cancer Research Group
Official(s) and/or principal investigator(s):
Miguel MartÃn, MD., PhD., Study Chair, Affiliation: Spanish Breast Cancer Research Group (GEICAM)
Miguel MartÃn, MD., PhD., Email: email@example.com
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.
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
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Primary outcome: Disease-free survival
Quality of life
Prognostic gene profile
Minimum age: 18 Years.
Maximum age: 70 Years.
- 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
- Laboratory results (within 14 days prior to randomization):
- Hematology: neutrophils >= 1. 5 x 10^9/l; platelets >= 100x 10^9/l; hemoglobin >=
- 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
- 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.
- Prior systemic therapy for breast cancer.
- Prior therapy with anthracyclines or taxanes (paclitaxel or docetaxel) for any
- 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
- Concomitant treatment with other therapy for cancer.
Locations and Contacts
Miguel MartÃn, MD., PhD., Email: firstname.lastname@example.org
Spanish Breast Cancer Research Group (GEICAM), San SebastiÃ¡n de los Reyes, Madrid 28700, Spain; Recruiting
Esther Mahillo, PhD, Phone: Â´+34916592870, Email: email@example.com
Ana Lluch, Principal Investigator
Miguel MartÃn, Principal Investigator
Lourdes Calvo, Principal Investigator
Amparo Ruiz, Principal Investigator
Sonia GonzÃ¡lez, Principal Investigator
AgustÃ Barnadas, Principal Investigator
Mireia MargelÃ, Principal Investigator
Ãlvaro RodrÃguez-Lescure, Principal Investigator
Miguel A SeguÃ, Principal Investigator
Monserrat MuÃ±oz, Principal Investigator
Antonio AntÃ³n, Principal Investigator
Manuel Ruiz-Borrego, Principal Investigator
RamÃ³n Colomer, Principal Investigator
Enrique Espinosa, Principal Investigator
JosÃ© Manuel LÃ³pez.Vega, Principal Investigator
Pedro SÃ¡nchez-Rovira, Principal Investigator
CÃ©sar A RodrÃguez, Principal Investigator
Nuria Ribelles, Principal Investigator
Encarna Adrover, Principal Investigator
Blanca MunÃ¡rriz, Principal Investigator
Carmen Crespo, Principal Investigator
Raquel AndrÃ©s, Principal Investigator
Manuel Ramos, Principal Investigator
Javier Salvador, Principal Investigator
Adolfo Frau, Principal Investigator
CÃ©sar Mendiola, Principal Investigator
JosÃ© R Mel-Lorenzo, Principal Investigator
JosÃ© I ChacÃ³n, Principal Investigator
Arrate Plazaola, Principal Investigator
Carlos Jara, Principal Investigator
Rosa MÂª Franquesa, Principal Investigator
Juan de la Haba, Principal Investigator
JosÃ© M Baena, Principal Investigator
Amparo Oltra, Principal Investigator
Alberto Arcediano del Amo, Principal Investigator
Angela Arcusa, Principal Investigator
Miguel MÃ©ndez, Principal Investigator
Amalia Velasco, Principal Investigator
JosÃ© AlÃ©s, Principal Investigator
Francisco J Carabantes, Principal Investigator
Severina DomÃnguez, Principal Investigator
Vicente CaraÃ±ana, Principal Investigator
Alfonso Modolell, Principal Investigator
Ricardo Cubedo, Principal Investigator
MÂª JosÃ© GarcÃa, Principal Investigator
JesÃºs GarcÃa-GirÃ³n, Principal Investigator
JesÃºs FloriÃ¡n, Principal Investigator
Antonio FernÃ¡ndez-Aramburo, Principal Investigator
Norberto Batista, Principal Investigator
Alberto Arizcum, Principal Investigator
Adolfo Murias, Principal Investigator
JesÃºs GarcÃa-Mata, Principal Investigator
Isabel Ãlvarez, Principal Investigator
Ana MÂª Miguel, Principal Investigator
Cristina MartÃn, Principal Investigator
Amadeu PelegrÃ, Principal Investigator
JosÃ© V Ãlvarez, Principal Investigator
Click here for more information about this study: GEICAM 2003-02
Starting date: September 2003
Ending date: December 2011
Last updated: September 4, 2007