FAC Versus FAC Plus Weekly Paclitaxel as Adjuvant Treatment of Node Negative High Risk Breast Cancer Patients

NCT ID: NCT00129389

Last Updated: 2023-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1925 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-09-19
• Study Completion Date: 2013-10-01

Brief Summary

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).

Detailed Description

Patients will be randomized to:

• Fluorouracil, doxorubicin, and cyclophosphamide (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) → Paclitaxel 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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: FAC

FAC X 6 The standard arm consisted of six cycles of FAC (fluorouracil 500 mg/m2, doxorubicin 50mg/m2, and cyclophosphamide 500mg/m2) administered once every 3 weeks.

Group Type: ACTIVE_COMPARATOR

Fluorouracil

Intervention Type: DRUG

Arm A: FAC Arm B: FAC-wP

Doxorubicin

Intervention Type: DRUG

Arm A: FAC Arm B: FAC-wP

Cyclophosphamide

Intervention Type: DRUG

Arm A: FAC Arm B: FAC-wP

Arm B: FAC-wP

FAC X 4 + 8 weekly Paclitaxel (wP) Patients in the experimental arm received four cycles of the FAC regimen followed by eight weekly administrations of paclitaxel (100mg/m2 per dose)

Group Type: EXPERIMENTAL

Fluorouracil

Intervention Type: DRUG

Arm A: FAC Arm B: FAC-wP

Doxorubicin

Intervention Type: DRUG

Arm A: FAC Arm B: FAC-wP

Cyclophosphamide

Intervention Type: DRUG

Arm A: FAC Arm B: FAC-wP

Paclitaxel

Intervention Type: DRUG

Arm B: FAC-wP

Interventions

Fluorouracil

Arm A: FAC Arm B: FAC-wP

Intervention Type: DRUG

Doxorubicin

Arm A: FAC Arm B: FAC-wP

Intervention Type: DRUG

Cyclophosphamide

Arm A: FAC Arm B: FAC-wP

Intervention Type: DRUG

Paclitaxel

Arm B: FAC-wP

Intervention Type: DRUG

Other Intervention Names

Adrucil; Caelyx; Cytoxan; taxol

Eligibility Criteria

Inclusion Criteria

• Written informed consent.
• Histological diagnoses of operable invasive adenocarcinoma of the breast (T1-T3). Tumors must be Human Epidermal Growth Factor Receptor 2 (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 Progesterone Receptor (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 Immunohistochemistry (IHC) 0 or +1 are eligible. For patients with IHC 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); Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <= 2.5 UNL; alkaline phosphatase <= 2.5 UNL. If values of AST and ALT > 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 by the National Cancer Institute Common Toxicity Criteria (NCICTC) v-2.0.
• Any other serious medical pathology, such as congestive heart failure, unstable angina, history of myocardial infarction during the previous year, uncontrolled hypertension 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Spanish Breast Cancer Research Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Hospital Universitario San Carlos

Locations

Hospital General Univ. De Elche

Elche, Alicante, Spain

Hospital General de Elda

Elda, Alicante, Spain

Complejo Hospitalario de Manresa

Manresa, Barcelona, Spain

Consorci Sanitari Parc Tauli

Sabadell, Barcelona, Spain

Hospital del Espíritu Santo

Santa Coloma de Gramenet, Barcelona, Spain

Consorci Sanitari Terrassa

Terrassa, Barcelona, Spain

Hospital Mutua Terrassa

Terrassa, Barcelona, Spain

Hospital General Jerez de la Frontera

Jerez de la Frontera, Cadiz, Spain

Hospital Provincial de Castellón

Castellon, Castellón, Spain

Hospital Comarcal de Barbastro

Barbastro, Huesca, Spain

Hospital Insular de Gran Canaria

Las Palmas de Gran Canaria, Las Palmas, Spain

Fundación Hospital de Alcorcón

Alcorcón, Madrid, Spain

Hospital Madrid- Montepríncipe

Boadilla del Monte, Madrid, Spain

Hospital de Móstoles

Móstoles, Madrid, Spain

Hospital Virgen de la Arrixaca

El Palmar, Murcia, Spain

Hospital Policlínico Vigo POVISA

Vigo, Pontevedra, Spain

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Santa Cruz De Tenerife, Spain

Hospital Sant Joan de Reus

Reus, Tarragona, Spain

Hospital de la Ribera

Alzira, Valencia, Spain

Complejo Hospitalario Juan Canalejo

A Coruña, , Spain

Centro Oncológico de Galicia

A Coruña, , Spain

Complejo Hospitalario de Albacete

Albacete, , Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital Virgen de los Lirios

Alicante, , Spain

Hospital Germans Trias i Pujol

Badalona, , Spain

Hospital del Mar

Barcelona, , Spain

Clínica Corochan S.A.

Barcelona, , Spain

Hospital Clinic i Provincial

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital General de Vic

Barcelona, , Spain

Hospital de Basurto

Bilbao, , Spain

Hospital General Yagüe

Burgos, , Spain

Hospital Puerta del Mar

Cadiz, , Spain

Hospital General de Ciudad Real

Ciudad Real, , Spain

Hospital Reina Sofía

Córdoba, , Spain

Hospital Virgen de la Luz

Cuenca, , Spain

ICO Hospital Universitari Josep Trueta

Girona, , Spain

Hospital General de Guadalajara

Guadalajara, , Spain

Complejo Hospitalario de Jaén

Jaén, , Spain

Hospital Xeral Calde

Lugo, , Spain

Hospital Universitario La Princesa

Madrid, , Spain

Hospital Doce de Octubre

Madrid, , Spain

Hospital Ramón y Cajal

Madrid, , Spain

Hospital Ruber Internacional

Madrid, , Spain

Hospital Puerta de Hierro

Madrid, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Hospital La Paz

Madrid, , Spain

CIOCC Hospital Norte-Sanchinarro

Madrid, , Spain

Complejo Hospitalario Virgen de la Victoria

Málaga, , Spain

Hospital Carlos Haya

Málaga, , Spain

Hospital Morales Messeguer

Murcia, , Spain

Hospital Sta María Nai

Ourense, , Spain

Hospital General Río Carrión

Palencia, , Spain

Hospital Clínico Universitario de Salamanca

Salamanca, , Spain

Instituto Oncológico de Guipuzcoa

San Sebastián, , Spain

Hospital de Donostia

San Sebastián, , Spain

Hospital Universitario Marqués de Valdecilla

Santander, , Spain

Hospital Univ. Virgen del Rocío

Seville, , Spain

Hospital Universitario de Valme

Seville, , Spain

Hospital Virgen de la Salud

Toledo, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Instituto Valenciano de Oncología

Valencia, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Hospital Arnau de Vilanova

Valencia, , Spain

Hospital Txagorritxu

Vitoria-Gasteiz, , Spain

Hospital Provincial de Zamora

Zamora, , Spain

Hospital Lozano Blesa

Zaragoza, , Spain

Hospital Miguel Servet

Zaragoza, , Spain

Countries

Spain

References

Martin M, Ruiz A, Ruiz Borrego M, Barnadas A, Gonzalez S, Calvo L, Margeli Vila M, Anton A, Rodriguez-Lescure A, Segui-Palmer MA, Munoz-Mateu M, Dorca Ribugent J, Lopez-Vega JM, Jara C, Espinosa E, Mendiola Fernandez C, Andres R, Ribelles N, Plazaola A, Sanchez-Rovira P, Salvador Bofill J, Crespo C, Carabantes FJ, Servitja S, Chacon JI, Rodriguez CA, Hernando B, Alvarez I, Carrasco E, Lluch A. Fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus FAC followed by weekly paclitaxel as adjuvant therapy for high-risk, node-negative breast cancer: results from the GEICAM/2003-02 study. J Clin Oncol. 2013 Jul 10;31(20):2593-9. doi: 10.1200/JCO.2012.46.9841. Epub 2013 Jun 3.

Reference Type: RESULT

PMID: 23733779 (View on PubMed)

Related Links

http://www.geicam.org

Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

Other Identifiers

2005-003109-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GEICAM 2003-02

Identifier Type: -

Identifier Source: org_study_id