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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: Docetaxel; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: 5-fluorouracil

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 Type: Interventional
• Enrollment (Actual): 1060
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Madrid
    • San Sebastián de los Reyes, Madrid, Spain, 28700
      • Spanish Breast Cancer Research Group

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: Cyclophosphamide; Other Names: cytoxan; Drug: Doxorubicin; Other Names: adriamycin; Drug: 5-fluorouracil; Other Names: Adrucil
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 Names: Taxotere; Drug: Cyclophosphamide; Other Names: cytoxan; Drug: Doxorubicin; Other Names: adriamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival (DFS) Events	DFS is calculated from the date of randomization until the first date of recurrence local, regional or distant, second primary tumor or death.	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was determined from the date of randomization until the date of death for any reason. OS is calculated from the date of randomization up to the first date of death by any cause.	10 years
The Number of Participants Who Experienced Adverse Events (AE)	Safety was assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 1.0.	Through study treatment, and average of 4 months
Best Score During Study for Global Health Status Scale	The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was used. Questionnaires were 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 Global Health Status Scale has been used, which is calculated with questions 29 and 30 from the EORTC QLQ-C30. From this scale, the best score is the highest score observed during study (of all the questionnaires completed by patient). In this scale, scores range from 0 to 100 and a high score represents a high level of functioning or HRQoL.	120 weeks
Number of Disease Free Survival Events in Hormone-receptor Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Positive Status Subgroup	Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first.	10 year
Disease Free Survival in Hormonal Receptor Positive and HER2 Negative Subgroup	Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first.	10 year
Disease Free Survival in Hormonal Receptor Negative and HER2 Positive Subgroup	Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally.	10 year
Disease Free Survival in Hormonal Receptor Negative and HER2 Negative Subgroup	Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first.	10 year

Collaborators and Investigators

• Sponsor: Spanish Breast Cancer Research Group
• Collaborators: Sanofi
• Investigators: Study Director: Study Director, Hospital Universitario San Carlos

Publications and helpful links

General 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. doi: 10.1056/NEJMoa043681.
• Martin M, Segui MA, Anton A, Ruiz A, Ramos M, Adrover E, Aranda I, Rodriguez-Lescure A, Grosse R, Calvo L, Barnadas A, Isla D, Martinez del Prado P, Ruiz Borrego M, Zaluski J, Arcusa A, Munoz M, Lopez Vega JM, Mel JR, Munarriz B, Llorca C, Jara C, Alba E, Florian J, Li J, Lopez Garcia-Asenjo JA, Saez A, Rios MJ, Almenar S, Peiro 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.

Helpful Links

• home page of the Spanish Breast Cancer Research Group

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 1999
• Primary Completion (Actual): December 2, 2010
• Study Completion (Actual): March 6, 2013

Study Registration Dates

• First Submitted: July 18, 2005
• First Submitted That Met QC Criteria: July 18, 2005
• First Posted (Estimate): July 21, 2005

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Quality of life; High risk node negative breast cancer; Disease-Free survival
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Fluorouracil; Doxorubicin
• Other Study ID Numbers: GEICAM 9805; TAX.ES1.301 (Other Identifier: RHÔNE-POULENC RORER, S.A. (RPR))