Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant Treatment

• ClinicalTrials.gov Identifier: NCT00121992
• Recruitment Status: Completed
• First Posted: July 21, 2005
• Last Update Posted: February 18, 2019
• Sponsor: Spanish Breast Cancer Research Group
• Collaborator: Sanofi
• Information provided by (Responsible Party): Spanish Breast Cancer Research Group

Study Description

Brief Summary:

This is a prospective, non-blinded randomized phase III trial. Patients will be post-surgically stratified at inclusion first according to the participating institution, then according to menopausal status and will be randomly assigned to receive either:

• TAC: Docetaxel 75 mg/m2 as a 1 hour intravenous (i.v.) infusion on day 1 every 3 weeks (q3w) in combination with doxorubicin 50 mg/m2 as an i.v. bolus and cyclophosphamide 500 mg/m2 as an i.v. bolus on day 1 every 3 weeks.
• FAC: 5-fluorouracil 500 mg/m2 as an i.v. bolus on day 1 every 3 weeks in combination with doxorubicin 50 mg/m2 as an i.v. bolus and cyclophosphamide 500 mg/m2 as an i.v. bolus on day 1 every 3 weeks.

Condition or disease	Intervention/treatment	Phase
Breast Neoplasms	Drug: Docetaxel; Drug: 5-fluorouracil; Drug: Doxorubicin; Drug: Cyclophosphamide	Phase 3

Detailed Description:

Primary objective:

• To compare disease-free survival (DFS) after treatment with docetaxel in combination with doxorubicin and cyclophosphamide (TAC) to 5-Fluorouracil in combination with doxorubicin and cyclophosphamide (FAC) as adjuvant treatment of high risk operable breast cancer patients with negative axillary lymph nodes.

Secondary objectives:

• To compare overall survival (OS) between the 2 above mentioned arms.
• To compare toxicity and quality of life between the 2 above mentioned arms.
• To evaluate pathologic markers for predicting efficacy (hormonal receptors and human epidermal growth factor receptor 2 (HER2) protein expression).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1059 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Randomized Comparing Docetaxel, Doxorubicin and Cyclophosphamide (TAC) vs 5-Fluorouracil, Doxorubicin and Cyclophosphamide (FAC) as Adjuvant Treatment of High Risk Operable Breast Cancer Patients With Negative Axillary Lymph Nodes
• Actual Study Start Date: July 1999
• Actual Primary Completion Date: December 2, 2010
• Actual Study Completion Date: March 6, 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm A: FAC; FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv	Drug: 5-fluorouracil; Other Name: Adrucil; Drug: Doxorubicin; Other Name: adriamycin; Drug: Cyclophosphamide; Other Name: cytoxan
Experimental: Arm B: TAC; TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv	Drug: Docetaxel; Other Name: Taxotere; Drug: Doxorubicin; Other Name: adriamycin; Drug: Cyclophosphamide; Other Name: cytoxan

Outcome Measures

Primary Outcome Measures :

1. Disease-free survival (DFS) [ Time Frame: 10 year ]
   DFS is calculated from the date of randomization until the first date of recurrence local, regional or distant, second primary tumor or death.

Secondary Outcome Measures :

1. Overall survival (OS) [ Time Frame: 10 year ]
   OS will be determined from the date of randomization until the date of death for any reason.
2. The Number of Participants Who Experienced Adverse Events (AE) [ Time Frame: Through study treatment ]
   Safety was assessed by standard clinical and laboratory tests. AE grade were defined by the NCI CTCAE v 1.0.
3. Health related quality of life (HRQoL) [ Time Frame: Up to 120 weeks ]
   HRQoL was self-administered to patients during the 14 days prior to randomisation baseline), at six prospective time points corresponding to chemotherapy cycles, with the time window related to each chemotherapy cycle defined as the period between the day following the first chemotherapy dose of the corresponding cycle and the day of the first dose of the following cycle, and then at 44, 68 and 120 weeks of the study.The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the breast cancer-specific quality-of-life questionnaire module (QLQ-BR23) were used.
4. Pathological and molecular markers to predict efficacy [ Time Frame: 10 year ]
   Hormone-receptor status and HER2 protein expression will be analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and will be processed centrally.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Written informed consent
• Operable breast cancer patients (T1-T3) with negative axillary lymph nodes (10 axillary nodes dissection) and high risk criteria according to St. Gallen consensus criteria.
• Histologically proven breast cancer. Interval between surgery and registration is less than 60 days.
• Definitive surgical treatment must be either mastectomy, or breast conservative surgery. Margins of resected specimen from surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma in-situ (DCIS). Lobular carcinoma in-situ is not considered as positive margin.
• Patients without proven metastatic disease.
• Estrogen and progesterone receptors performed on the primary tumour prior to randomization.
• Age between 18 years and 70 years.
• Karnofsky performance status index > 80 %.
• Adequate hepatic, renal and heart functions.
• Adequate hematology levels.
• Negative pregnancy test

Exclusion Criteria:

• Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
• Prior anthracycline therapy or taxoids (paclitaxel, docetaxel) for any malignancy.
• Prior radiation therapy for breast cancer.
• Bilateral invasive breast cancer.
• Pregnant, or lactating patients.
• Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment .
• Any T4 or N1-3 or M1 breast cancer.
• Pre-existing motor or sensory neurotoxicity of a severity grade 2 by NCI criteria.
• Other serious illness or medical condition
• Past or current history of neoplasm other than breast carcinoma.
• Ipsilateral ductal carcinoma in-situ (DCIS) of the breast.
• Lobular carcinoma in-situ (LCIS) of the breast.
• Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose
• Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment should be stopped before study entry.
• Definite contraindications for the use of corticosteroids.
• Concurrent treatment with other experimental drugs.
• Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
• Concurrent treatment with any other anti-cancer therapy.
• Male patients.

Contacts and Locations

Locations

Spain

Spanish Breast Cancer Research Group

San Sebastián de los Reyes, Madrid, Spain, 28700

Sponsors and Collaborators

Spanish Breast Cancer Research Group

Sanofi

Investigators

• Study Director: Study Director; Hospital Universitario San Carlos

More Information

Additional Information:

home page of the Spanish Breast Cancer Research Group 

Publications:

Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, Guevin R, Howell A, Fornander T, Hainsworth J, Coleman R, Vinholes J, Modiano M, Pinter T, Tang SC, Colwell B, Prady C, Provencher L, Walde D, Rodriguez-Lescure A, Hugh J, Loret C, Rupin M, Blitz S, Jacobs P, Murawsky M, Riva A, Vogel C; Breast Cancer International Research Group 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Martín M, Seguí MA, Antón A, Ruiz A, Ramos M, Adrover E, Aranda I, Rodríguez-Lescure A, Grosse R, Calvo L, Barnadas A, Isla D, Martinez del Prado P, Ruiz Borrego M, Zaluski J, Arcusa A, Muñoz M, López Vega JM, Mel JR, Munarriz B, Llorca C, Jara C, Alba E, Florián J, Li J, López García-Asenjo JA, Sáez A, Rios MJ, Almenar S, Peiró G, Lluch A; GEICAM 9805 Investigators. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med. 2010 Dec 2;363(23):2200-10. doi: 10.1056/NEJMoa0910320.

• Responsible Party: Spanish Breast Cancer Research Group
• ClinicalTrials.gov Identifier: NCT00121992
• Other Study ID Numbers: GEICAM 9805; TAX.ES1.301 ( Other Identifier: RHÔNE-POULENC RORER, S.A. (RPR) )
• First Posted: July 21, 2005
• Last Update Posted: February 18, 2019
• Last Verified: February 2019

Keywords provided by Spanish Breast Cancer Research Group:

High risk node negative breast cancer; Disease-Free survival; Quality of life

Additional relevant MeSH terms:

Breast Neoplasms; Breast Diseases; Neoplasms by Site; Neoplasms; Skin Diseases; Cyclophosphamide; Docetaxel; Doxorubicin; Fluorouracil; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Antimetabolites; Antimetabolites, Antineoplastic