Clinical trial NCT00121992: Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Neoplasms
Keywords: High risk node negative breast cancer
Disease-Free survival
Quality of life
Lead sponsor: Spanish Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2005-07-21
Enrollment: 1060
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility 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.

Primary outcomes:
measure: Disease-free Survival (DFS) Events
timeFrame: 10 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 10 years
measure: The Number of Participants Who Experienced Adverse Events (AE)
timeFrame: Through study treatment, and average of 4 months
measure: Best Score During Study for Global Health Status Scale
timeFrame: 120 weeks
measure: Number of Disease Free Survival Events in Hormone-receptor Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Positive Status Subgroup
timeFrame: 10 year
measure: Disease Free Survival in Hormonal Receptor Positive and HER2 Negative Subgroup
timeFrame: 10 year
measure: Disease Free Survival in Hormonal Receptor Negative and HER2 Positive Subgroup
timeFrame: 10 year
measure: Disease Free Survival in Hormonal Receptor Negative and HER2 Negative Subgroup
timeFrame: 10 year
Other outcomes:
Locations:
city: San Sebastián de los Reyes
country: Spain
facility: Spanish Breast Cancer Research Group
state: Madrid
Study officials:
affiliation: Hospital Universitario San Carlos
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.