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

Breast Cancer Clinical Trial

Official title:

Multicenter Randomized Phase III Trial to Compare 6 FAC Cycles vs 4 FAC Cycles Followed by 8 Weekly Paclitaxel Administrations, as Adjuvant Treatment for Node Negative Operable Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00129389
• Other study ID #: GEICAM 2003-02
• Secondary ID: 2005-003109-10
• Status: Completed
• Phase: Phase 3
• Start date: September 19, 2003
• Est. completion date: October 1, 2013

Study information

• Verified date: March 2023
• Source: Spanish Breast Cancer Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1925
• Est. completion date: October 1, 2013
• Est. primary completion date: October 1, 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Fluorouracil
Arm A: FAC Arm B: FAC-wP
• Doxorubicin
Arm A: FAC Arm B: FAC-wP
• Cyclophosphamide
Arm A: FAC Arm B: FAC-wP
• Paclitaxel
Arm B: FAC-wP

Locations

Country	Name	City	State
Spain	Centro Oncológico de Galicia	A Coruña
Spain	Complejo Hospitalario Juan Canalejo	A Coruña
Spain	Complejo Hospitalario de Albacete	Albacete
Spain	Fundación Hospital de Alcorcón	Alcorcón	MAdrid
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Virgen de los Lirios	Alicante
Spain	Hospital de la Ribera	Alzira	Valencia
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Comarcal de Barbastro	Barbastro	Huesca
Spain	Clínica Corochan S.A.	Barcelona
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital General de Vic	Barcelona
Spain	Hospital de Basurto	Bilbao
Spain	Hospital Madrid- Montepríncipe	Boadilla Del Monte	Madrid
Spain	Hospital General Yagüe	Burgos
Spain	Hospital Puerta del Mar	Cadiz
Spain	Hospital Provincial de Castellón	Castellón De La Plana	Castellón
Spain	Hospital General de Ciudad Real	Ciudad Real
Spain	Hospital Reina Sofía	Córdoba
Spain	Hospital Virgen de la Luz	Cuenca
Spain	Hospital Virgen de la Arrixaca	El Palmar	Murcia
Spain	Hospital General Univ. De Elche	Elche	Alicante
Spain	Hospital General de Elda	Elda	Alicante
Spain	ICO Hospital Universitari Josep Trueta	Gerona
Spain	Hospital General de Guadalajara	Guadalajara
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Hospital General Jerez de la Frontera	Jerez De La Frontera	Cadiz
Spain	Hospital Universitario de Canarias	La Laguna	Santa Cruz De Tenerife
Spain	Hospital Insular de Gran Canaria	Las Palmas De Gran Canaria	Las Palmas
Spain	Hospital Xeral Calde	Lugo
Spain	CIOCC Hospital Norte-Sanchinarro	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Doce de Octubre	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital Puerta de Hierro	MAdrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Ruber Internacional	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Complejo Hospitalario Virgen de la Victoria	Málaga
Spain	Hospital Carlos Haya	Málaga
Spain	Complejo Hospitalario de Manresa	Manresa	Barcelona
Spain	Hospital de Móstoles	Móstoles	MAdrid
Spain	Hospital Morales Messeguer	Murcia
Spain	Hospital Sta María Nai	Orense
Spain	Hospital General Río Carrión	Palencia
Spain	Hospital Sant Joan de Reus	Reus	Tarragona
Spain	Consorci Sanitari Parc Tauli	Sabadell	Barcelona
Spain	Hospital Clínico Universitario de Salamanca	Salamanca
Spain	Hospital de Donostia	San Sebastián
Spain	Instituto Oncológico de Guipuzcoa	San Sebastián
Spain	Hospital del Espíritu Santo	Santa Coloma De Gramenet	Barcelona
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Univ. Virgen del Rocío	Sevilla
Spain	Hospital Universitario de Valme	Sevilla
Spain	Consorci Sanitari Terrassa	Terrassa	Barcelona
Spain	Hospital Mutua Terrassa	Terrassa	Barcelona
Spain	Hospital Virgen de la Salud	Toledo
Spain	Hospital Arnau de Vilanova	Valencia
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario La Fe	Valencia
Spain	Instituto Valenciano de Oncología	Valencia
Spain	Hospital Policlínico Vigo POVISA	Vigo	Pontevedra
Spain	Hospital Txagorritxu	Vitoria
Spain	Hospital Provincial de Zamora	Zamora
Spain	Hospital Lozano Blesa	Zaragoza
Spain	Hospital Miguel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Spanish Breast Cancer Research Group	Bristol-Myers Squibb

Country where clinical trial is conducted

Spain, 

References & Publications (1)

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, S — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival (DFS) Event	DFS is defined as the evidence of local, regional or metastatic recurrence, second primary cancer (with the exception of carcinoma of squamous cells or basal cells of the skin, cervical carcinoma in situ or lobular or ductal carcinoma in situ of the breast) or death for any reason.	Up to 5 years
Secondary	Overall Survival (OS) Event	OS event is defined as the death from any cause.	Up to 5 years

External Links

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