Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant Treatment
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| ClinicalTrials.gov Identifier: NCT00121992 |
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Recruitment Status :
Completed
First Posted : July 21, 2005
Results First Posted : December 4, 2020
Last Update Posted : December 4, 2020
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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 |
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 (Clinical Trial) |
| Actual Enrollment : | 1060 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 |
| Arm | Intervention/treatment |
|---|---|
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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
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Drug: 5-fluorouracil
Other Name: Adrucil Drug: Doxorubicin Other Name: adriamycin Drug: Cyclophosphamide Other Name: cytoxan |
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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
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Drug: Docetaxel
Other Name: Taxotere Drug: Doxorubicin Other Name: adriamycin Drug: Cyclophosphamide Other Name: cytoxan |
- Disease-free Survival (DFS) Events [ Time Frame: 10 years ]DFS is calculated from the date of randomization until the first date of recurrence local, regional or distant, second primary tumor or death.
- Overall Survival (OS) [ Time Frame: 10 years ]
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.
- The Number of Participants Who Experienced Adverse Events (AE) [ Time Frame: Through study treatment, and average of 4 months ]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.
- Best Score During Study for Global Health Status Scale [ Time Frame: 120 weeks ]
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.
- Number of Disease Free Survival Events in Hormone-receptor Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Positive Status Subgroup [ Time Frame: 10 year ]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.
- Disease Free Survival in Hormonal Receptor Positive and HER2 Negative Subgroup [ Time Frame: 10 year ]
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.
- Disease Free Survival in Hormonal Receptor Negative and HER2 Positive Subgroup [ Time Frame: 10 year ]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 in Hormonal Receptor Negative and HER2 Negative Subgroup [ Time Frame: 10 year ]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.
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00121992
| Spain | |
| Spanish Breast Cancer Research Group | |
| San Sebastián de los Reyes, Madrid, Spain, 28700 | |
| Study Director: | Study Director | Hospital Universitario San Carlos |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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 Key Record Dates |
| Results First Posted: | December 4, 2020 |
| Last Update Posted: | December 4, 2020 |
| Last Verified: | November 2020 |
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High risk node negative breast cancer Disease-Free survival Quality of life |
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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 |