Breast NeoplasmsPhase 3NCT00021255
Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer
A Phase 3 study testing Doxorubicin, Cyclophosphamide and Docetaxel in people with Breast Neoplasms, run by Sanofi at 42 sites in 42 countries.
Trial summary
Primary objective: Compare disease-free survival in women with human epidermal growth factor receptor 2 (HER2)-neu-expressing node-positive or high-risk node-negative operable breast cancer treated with adjuvant doxorubicin, cyclophosphamide, and docetaxel with or without trastuzumab (Herceptin) vs trastuzumab… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- Doxorubicin, Cyclophosphamide and Docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,222 participants
- Where
- 42 sitesin 42 countries
- Study dates
- Apr 2001to Dec 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the participants for treatment and follow-up.
- Accessible for treatment and follow-up at participating centers.
- Histologically proven breast cancer with an interval between definitive surgery that included axillary lymph node involvement assessment and registration of less than or equal to 60 days. A central pathology review might be performed post randomization for confirmation of diagnosis and molecular studies. The same block used for HER2neu determination prior to randomization might be used for the central pathology review.
- Definitive surgical treatment must be either mastectomy with axillary lymph node involvement assessment, or breast conserving surgery with axillary lymph node involvement assessment for operable breast cancer (T1-3, Clinical N0-1, M0). Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and/or ductal carcinoma in situ (DCIS).
- Participants must be either lymph node positive or high risk node negative. Lymph node positive participants were to be defined as participants having invasive adenocarcinoma with at least one axillary lymph node (pN1) showing evidence of tumor among a minimum of six resected lymph nodes. High risk lymph node negative participants were to be defined as participants having invasive adenocarcinoma with either 0 (pNo) among a minimum of 6 resected lymph nodes or negative sentinel node biopsy (pNo) and at least one of the following factors: tumor size > 2 cm, estrogen receptor (ER) and/or progesteron receptor (PR) status was negative, histologic and/or nuclear grade 2-3, or age < 35 years.
- Tumor must show the presence of the HER2neu gene amplification by Fluorescence In-Situ Hybridization (FISH analysis) by a designated central laboratory.
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- Estrogen and/or progesterone receptor analysis performed on the primary tumor prior to randomization. Results must be known at the time of randomization.
- Karnofsky Performance status index ≥ 80%.
- Normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF) (multiple-gated acquisition [MUGA] scan) and electrocardiogram (ECG) within 3 months prior to registration. The result of the MUGA must be equal to or above the lower limit of normal for the institution.
- Laboratory requirements: (within 14 days prior to registration)
- Hematology: i) Neutrophils ≥ 2.0 109/L ii) Platelets ≥ 100 109/L iii) Hemoglobin ≥ 10 g/Dl
- Hepatic function: i) Total bilirubin ≤ 1 UNL ii) Aspartate aminotransferase (ASAT) (Serum glutamic oxaloacetic transaminase [SGOT]) and alanine amino transferase (ALAT) (Serum glutamic-pyruvic transaminase [SGPT]) ≤ 2.5 UNL iii) Alkaline phosphatase ≤ 5 UNL iv) Participants with ASAT and/or ALAT > 1.5 x UNL associated with alkaline phosphatase > 2.5 x UNL are not eligible for the study.
- Renal function: i) Creatinine ≤ 175 µmol/L (2 mg/dL) ii) If creatinine was 140 - 175 μmol/L, the calculated creatinine clearance should be ≥ 60 mL/min.
- Complete staging work-up within 3 months prior to registration. All participants had bilateral mammography, chest X-ray (posterioanterior [PA] and lateral) and/or computerized tomography (CT) and/or magnetic resonance imaging (MRI), abdominal ultrasound and/or CT scan and/or MRI, and bone scan. In cases of positive bone scans, bone X-ray evaluation was mandatory to rule out the possibility of metastatic bone scan positivity. Other tests may be performed as clinically indicated.
- Negative pregnancy test (urine or serum) within 7 days prior to registration for all women of childbearing potential.
- An audiology assessment with normal results was to be performed within 4 weeks of registration. This was only for those centers who had selected cisplatin as their platinum salt of choice for the BCIRG 006 study.
Who cannot join
- Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
- Prior anthracycline therapy, taxoids (paclitaxel, docetaxel) or platinum salts for any malignancy.
- Prior radiation therapy for breast cancer.
- Bilateral invasive breast cancer.
- Pregnant, or lactating participants. Participants of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment (chemotherapy and tamoxifen therapy) and must had negative urine or serum pregnancy test within 7 days prior to registration.
- Any T4 or N2 or known N3 or M1 breast cancer.
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- Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by National Cancer Institute (NCI) criteria.
- Cardiac disease that would preclude the use of doxorubicin, docetaxel and Herceptin:
- any documented myocardial infarction
- angina pectoris that required the use of antianginal medication
- any history of documented congestive heart failure
- Grade 3 or Grade 4 cardiac arrhythmia (NCI Common Terminology Criteria [CTC], version 2.0)
- clinically significant valvular heart disease
- participants with cardiomegaly on chest x-ray or ventricular hypertrophy on ECG, unless they demonstrate by MUGA scan within the past 3 months that the LVEF was ≥ the lower limit of normal for the radiology facility;
- participants with poorly controlled hypertension i.e. diastolic greater than 100 mm/Hg. (Participants who were well controlled on medication were eligible for entry)
- participants who currently received medications (digitalis, beta-blockers, calcium channel-blockers, etc) that altered cardiac conduction, if these medications were administered for cardiac arrhythmia, angina or congestive heart failure. If these medications were administered for other reasons (ie hypertension), the participant was eligible.
- Other serious illness or medical condition:
- history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
- active uncontrolled infection
- active peptic ulcer, unstable diabetes mellitus
- impaired hearing (only for those participants treated at centers who had selected cisplatin as their platinum salt of choice)
- Past or current history of neoplasm other than breast carcinoma, except for:
- curatively treated non-melanoma skin cancer
- in situ carcinoma of the cervix
- other cancer curatively treated and with no evidence of disease for at least 10 years
- ipsilateral DCIS of the breast
- lobular carcinoma in-situ (LCIS) of the breast
- Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention. Participants must had discontinued these agents prior to randomization.
- Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose (≤ 20 mg methylprednisolone or equivalent).
- Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must be stopped prior to randomization.
- 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.
- The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Trial locations and contacts
42 sites in 42 countries.
42 sites in 42 countries
United States1 site
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, 08807
Bosnia and Herzegovina1 site
Sanofi-Aventis Administrative Office
Sarajevo
United Kingdom1 site
Sanofi-Aventis Administrative Office
Guildford Surrey
About this study
Official title: Multicenter Phase III Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed By Docetaxel (AC-T) With Doxorubicin and Cyclophosphamide Followed By Docetaxel and Trastuzumab (Herceptin)(AC-TH) and With Docetaxel, Carboplatin and Trastuzumab (TCH) In The Adjuvant Treatment Of Node Positive and High Risk Node Negative Patients With Operable Breast Cancer Containing The HER2 Alteration
Primary objective:
- Compare disease-free survival in women with human epidermal growth factor receptor 2 (HER2)-neu-expressing node-positive or high-risk node-negative operable breast cancer treated with adjuvant doxorubicin, cyclophosphamide, and docetaxel with or without trastuzumab (Herceptin) vs trastuzumab, docetaxel, and carboplatin.
Read more
Secondary objective:
- Compare overall survival of participants treated with these regimens.
- Compare the toxic effects (including cardiac) of these regimens in these participants.
- Compare quality of life of participants treated with these regimens.
- Compare pathologic and molecular markers for predicting efficacy of these regimens in these participants.
- For substudy: Compare peripheral levels of shed HER2-neu extracellular domain with fluorescence in situ hybridization in predicting outcome in participants treated with these regimens.
- Conditions
- Breast Neoplasms
- Being tested
- Doxorubicin, Cyclophosphamide, Docetaxel, Herceptin, Carboplatin
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxorubicinDrug
CyclophosphamideDrug
DocetaxelDrug
Also called Taxotere
HerceptinDrug
Also called Trastuzumab
CarboplatinDrug
| Study group | Role | What they receive |
|---|---|---|
| Doxorubicin+Cyclophosphamide (AC) followed by Docetaxel (AC→T) | Experimental | Doxorubicin 60 mg/m² intravenous (IV) bolus injection in combination with cyclophosphamide 600 mg/m² IV bolus injection on Day 1 of every 3 weeks for 4 cycles followed by docetaxel 100 mg/m² IV infusion every 3 weeks for another 4 cycles. Receives: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
| AC followed by Docetaxel + Herceptin (AC→TH) | Experimental | Doxorubicin 60 mg/m² IV bolus injection in combination with cyclophosphamide 600 mg/m² IV bolus Injection on Day 1 of every 3 weeks for 4 cycles. Herceptin 4 mg/kg IV infusion on Day 1 of Cycle 5, followed by Herceptin 2 mg/kg by IV infusion weekly starting from Day 8; and docetaxel 100 mg/m² IV infusion on Day 2 of Cycle 5, then on Day 1 of every 3 weeks for all subsequent cycles ( total 4 cycles). After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose. Receives: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Herceptin |
| Docetaxel + Carboplatin + Herceptin (TCH) | Experimental | Herceptin 4 mg/kg IV infusion on Day 1 of Cycle 1 only, followed by Herceptin 2 mg/kg IV infusion weekly starting from Day 8 until three weeks after the last cycle of chemotherapy. Docetaxel 75 mg/ m² IV infusion on Day 2 of Cycle 1, then on Day 1 of all subsequent cycles followed by carboplatin IV infusion at target AUC = 6 mg/mL/min repeated every 3 weeks for a total of 6 cycles. After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg by IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose. Receives: Drug: Docetaxel; Drug: Herceptin; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Disease Free Survival at 5 Years
Disease Free Survival was 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 (with the exception of curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix) or death from any cause whichever occured first. Disease free survival was estimated using the Kaplan-Meier method.
Measured: From randomization until relapse or death or up to 5 years
Secondary outcomes (2)
Percentage of Participants With Disease Free Survival at 10 Years
Disease free survival was 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 (with the exception of curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix) or death from any cause whichever occured first. Disease free survival was estimated using the Kaplan-Meier method.
Measured: From randomization until relapse or death or up to 10 years
Overall Survival- Percentage of Participants Who Survived at 10 Years
Overall survival of the participants was measured from the date of randomization up to the date of death due to any cause. Overall survival was estimated using the Kaplan-Meier method.
Measured: From randomization until death or up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startApr 2001
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3,222 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cancer International Research Group (CIRG)
- Responsible party
- Sponsor
- Investigators
- AUSSEL Jean Philippe, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00021255
- Sponsor's protocol ID
- TAX_GMA_302
- Other IDs
- BCIRG 006
- Status last verified
- Sep 2016
- First submitted
- 11 Jul 2001
- Last updated
- 15 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. doi: 10.1056/NEJMoa0910383.
PubMed 21991949Au HJ, Eiermann W, Robert NJ, Pienkowski T, Crown J, Martin M, Pawlicki M, Chan A, Mackey J, Glaspy J, Pinter T, Liu MC, Fornander T, Sehdev S, Ferrero JM, Bee V, Santana MJ, Miller DP, Lalla D, Slamon DJ; Translational Research in Oncology BCIRG 006 Trial Investigators. Health-related quality of life with adjuvant docetaxel- and trastuzumab-based regimens in patients with node-positive and high-risk node-negative, HER2-positive early breast cancer: results from the BCIRG 006 Study. Oncologist. 2013;18(7):812-8. doi: 10.1634/theoncologist.2013-0091. Epub 2013 Jun 28.
PubMed 23814044Perez EA, Press MF, Dueck AC, Jenkins RB, Kim C, Chen B, Villalobos I, Paik S, Buyse M, Wiktor AE, Meyer R, Finnigan M, Zujewski J, Shing M, Stern HM, Lingle WL, Reinholz MM, Slamon DJ. Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG N9831, BCIRG 006, and BCIRG 005). Breast Cancer Res Treat. 2013 Feb;138(1):99-108. doi: 10.1007/s10549-013-2444-y. Epub 2013 Feb 19.
PubMed 23420271Press MF, Sauter G, Buyse M, Bernstein L, Guzman R, Santiago A, Villalobos IE, Eiermann W, Pienkowski T, Martin M, Robert N, Crown J, Bee V, Taupin H, Flom KJ, Tabah-Fisch I, Pauletti G, Lindsay MA, Riva A, Slamon DJ. Alteration of topoisomerase II-alpha gene in human breast cancer: association with responsiveness to anthracycline-based chemotherapy. J Clin Oncol. 2011 Mar 1;29(7):859-67. doi: 10.1200/JCO.2009.27.5644. Epub 2010 Dec 28.
PubMed 21189395Stern HM, Gardner H, Burzykowski T, Elatre W, O'Brien C, Lackner MR, Pestano GA, Santiago A, Villalobos I, Eiermann W, Pienkowski T, Martin M, Robert N, Crown J, Nuciforo P, Bee V, Mackey J, Slamon DJ, Press MF. PTEN Loss Is Associated with Worse Outcome in HER2-Amplified Breast Cancer Patients but Is Not Associated with Trastuzumab Resistance. Clin Cancer Res. 2015 May 1;21(9):2065-74. doi: 10.1158/1078-0432.CCR-14-2993. Epub 2015 Feb 3.
PubMed 25649019Blasco A, Lopez-Tarruella S, Urruticoechea A, Carrasco E, Spera G, Martin M, Bermejo B, Chap L, Ruiz-Borrego M, Crown J, Garcia-Saenz JA, Chan A, Guerrero-Zotano A, Semiglazov V, Calvo L, Pienkowski T, Herranz J, Slamon D. Intermediate endpoints as surrogates for long-term outcomes in breast cancer adjuvant chemotherapy trials. Oncologist. 2025 Sep 1;30(9):oyaf263. doi: 10.1093/oncolo/oyaf263.
PubMed 40838872Garcia-Saenz JA, Spera G, Pollan M, Bermejo B, Ruiz-Borrego M, Chan A, Martin M, Guerrero-Zotano A, Calvo L, Rodriguez-Lescure A, Marin M, Chap L, Crown J, Pienkowski T, Bee V, Casas M, Polonio O, Bezares S, Slamon D. Body mass index as a predictive factor for efficacy of adjuvant taxane-based chemotherapy in early-stage breast cancer patients: A pooled analysis from adjuvant GEICAM Spanish Breast Cancer Group and TRIO Translational Research in Oncology Group studies. Int J Cancer. 2025 Aug 15;157(4):709-721. doi: 10.1002/ijc.35432. Epub 2025 Apr 10.
PubMed 40207789Press MF, Sauter G, Buyse M, Fourmanoir H, Quinaux E, Tsao-Wei DD, Eiermann W, Robert N, Pienkowski T, Crown J, Martin M, Valero V, Mackey JR, Bee V, Ma Y, Villalobos I, Campeau A, Mirlacher M, Lindsay MA, Slamon DJ. HER2 Gene Amplification Testing by Fluorescent In Situ Hybridization (FISH): Comparison of the ASCO-College of American Pathologists Guidelines With FISH Scores Used for Enrollment in Breast Cancer International Research Group Clinical Trials. J Clin Oncol. 2016 Oct 10;34(29):3518-3528. doi: 10.1200/JCO.2016.66.6693.
PubMed 27573653
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Phase III Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed By Docetaxel (AC-T) With Doxorubicin and Cyclophosphamide Followed By Docetaxel and Trastuzumab (Herceptin)(AC-TH) and With Docetaxel, Carboplatin and Trastuzumab (TCH) In The Adjuvant Treatment Of Node Positive and High Risk Node Negative Patients With Operable Breast Cancer Containing The HER2 Alteration
- ClinicalTrials.gov ID
- NCT00021255
- Acronym / sponsor ID
- TAX_GMA_302
- Conditions
- Breast Neoplasms
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,222 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Cancer International Research Group (CIRG)
- Study start
- Apr 2001
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Posted 15 Nov 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary objective:
- Compare disease-free survival in women with human epidermal growth factor receptor 2 (HER2)-neu-expressing node-positive or high-risk node-negative operable breast cancer treated with adjuvant doxorubicin, cyclophosphamide, and docetaxel with or without trastuzumab (Herceptin) vs trastuzumab, docetaxel, and carboplatin.
Secondary objective:
- Compare overall survival of participants treated with these regimens.
- Compare the toxic effects (including cardiac) of these regimens in these participants.
- Compare quality of life of participants treated with these regimens.
- Compare pathologic and molecular markers for predicting efficacy of these regimens in these participants.
- For substudy: Compare peripheral levels of shed HER2-neu extracellular domain with fluorescence in situ hybridization in predicting outcome in participants treated with these regimens.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Doxorubicin+Cyclophosphamide (AC) followed by Docetaxel (AC→T) | Experimental | Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: DocetaxelDoxorubicin 60 mg/m² intravenous (IV) bolus injection in combination with cyclophosphamide 600 mg/m² IV bolus injection on Day 1 of every 3 weeks for 4 cycles followed by docetaxel 100 mg/m² IV infusion every 3 weeks for another 4 cycles. |
| AC followed by Docetaxel + Herceptin (AC→TH) | Experimental | Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: Docetaxel, Drug: HerceptinDoxorubicin 60 mg/m² IV bolus injection in combination with cyclophosphamide 600 mg/m² IV bolus Injection on Day 1 of every 3 weeks for 4 cycles. Herceptin 4 mg/kg IV infusion on Day 1 of Cycle 5, followed by Herceptin 2 mg/kg by IV infusion weekly starting from Day 8; and docetaxel 100 mg/m² IV infusion on Day 2 of Cycle 5, then on Day 1 of every 3 weeks for all subsequent cycles ( total 4 cycles). After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose. |
| Docetaxel + Carboplatin + Herceptin (TCH) | Experimental | Drug: Docetaxel, Drug: Herceptin, Drug: CarboplatinHerceptin 4 mg/kg IV infusion on Day 1 of Cycle 1 only, followed by Herceptin 2 mg/kg IV infusion weekly starting from Day 8 until three weeks after the last cycle of chemotherapy. Docetaxel 75 mg/ m² IV infusion on Day 2 of Cycle 1, then on Day 1 of all subsequent cycles followed by carboplatin IV infusion at target AUC = 6 mg/mL/min repeated every 3 weeks for a total of 6 cycles. After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg by IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the participants for treatment and follow-up.
- Accessible for treatment and follow-up at participating centers.
- Histologically proven breast cancer with an interval between definitive surgery that included axillary lymph node involvement assessment and registration of less than or equal to 60 days. A central pathology review might be performed post randomization for confirmation of diagnosis and molecular studies. The same block used for HER2neu determination prior to randomization might be used for the central pathology review.
- Definitive surgical treatment must be either mastectomy with axillary lymph node involvement assessment, or breast conserving surgery with axillary lymph node involvement assessment for operable breast cancer (T1-3, Clinical N0-1, M0). Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and/or ductal carcinoma in situ (DCIS).
- Participants must be either lymph node positive or high risk node negative. Lymph node positive participants were to be defined as participants having invasive adenocarcinoma with at least one axillary lymph node (pN1) showing evidence of tumor among a minimum of six resected lymph nodes. High risk lymph node negative participants were to be defined as participants having invasive adenocarcinoma with either 0 (pNo) among a minimum of 6 resected lymph nodes or negative sentinel node biopsy (pNo) and at least one of the following factors: tumor size > 2 cm, estrogen receptor (ER) and/or progesteron receptor (PR) status was negative, histologic and/or nuclear grade 2-3, or age < 35 years.
Key exclusion criteria (34 listed)
- Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
- Prior anthracycline therapy, taxoids (paclitaxel, docetaxel) or platinum salts for any malignancy.
- Prior radiation therapy for breast cancer.
- Bilateral invasive breast cancer.
- Pregnant, or lactating participants. Participants of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment (chemotherapy and tamoxifen therapy) and must had negative urine or serum pregnancy test within 7 days prior to registration.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Doxorubicin | Drug | AC followed by Docetaxel + Herceptin (AC→TH), Doxorubicin+Cyclophosphamide (AC) followed by Docetaxel (AC→T) |
| Cyclophosphamide | Drug | AC followed by Docetaxel + Herceptin (AC→TH), Doxorubicin+Cyclophosphamide (AC) followed by Docetaxel (AC→T) |
| DocetaxelAlso: Taxotere | Drug | AC followed by Docetaxel + Herceptin (AC→TH), Docetaxel + Carboplatin + Herceptin (TCH), Doxorubicin+Cyclophosphamide (AC) followed by Docetaxel (AC→T) |
| HerceptinAlso: Trastuzumab | Drug | AC followed by Docetaxel + Herceptin (AC→TH), Docetaxel + Carboplatin + Herceptin (TCH) |
| Carboplatin | Drug | Docetaxel + Carboplatin + Herceptin (TCH) |
Primary outcome
Percentage of Participants With Disease Free Survival at 5 Years
Time frame: From randomization until relapse or death or up to 5 years
Disease Free Survival was 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 (with the exception of curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix) or death from any cause whichever occured first. Disease free survival was estimated using the Kaplan-Meier method.
2 secondary outcomes
Percentage of Participants With Disease Free Survival at 10 Years
Time frame: From randomization until relapse or death or up to 10 years
Overall Survival- Percentage of Participants Who Survived at 10 Years
Time frame: From randomization until death or up to 10 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21991949Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. doi: 10.1056/NEJMoa0910383.
- Background: PubMed 23814044Au HJ, Eiermann W, Robert NJ, Pienkowski T, Crown J, Martin M, Pawlicki M, Chan A, Mackey J, Glaspy J, Pinter T, Liu MC, Fornander T, Sehdev S, Ferrero JM, Bee V, Santana MJ, Miller DP, Lalla D, Slamon DJ; Translational Research in Oncology BCIRG 006 Trial Investigators. Health-related quality of life with adjuvant docetaxel- and trastuzumab-based regimens in patients with node-positive and high-risk node-negative, HER2-positive early breast cancer: results from the BCIRG 006 Study. Oncologist. 2013;18(7):812-8. doi: 10.1634/theoncologist.2013-0091. Epub 2013 Jun 28.
- Background: PubMed 23420271Perez EA, Press MF, Dueck AC, Jenkins RB, Kim C, Chen B, Villalobos I, Paik S, Buyse M, Wiktor AE, Meyer R, Finnigan M, Zujewski J, Shing M, Stern HM, Lingle WL, Reinholz MM, Slamon DJ. Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG N9831, BCIRG 006, and BCIRG 005). Breast Cancer Res Treat. 2013 Feb;138(1):99-108. doi: 10.1007/s10549-013-2444-y. Epub 2013 Feb 19.
- Background: PubMed 21189395Press MF, Sauter G, Buyse M, Bernstein L, Guzman R, Santiago A, Villalobos IE, Eiermann W, Pienkowski T, Martin M, Robert N, Crown J, Bee V, Taupin H, Flom KJ, Tabah-Fisch I, Pauletti G, Lindsay MA, Riva A, Slamon DJ. Alteration of topoisomerase II-alpha gene in human breast cancer: association with responsiveness to anthracycline-based chemotherapy. J Clin Oncol. 2011 Mar 1;29(7):859-67. doi: 10.1200/JCO.2009.27.5644. Epub 2010 Dec 28.
- Background: PubMed 25649019Stern HM, Gardner H, Burzykowski T, Elatre W, O'Brien C, Lackner MR, Pestano GA, Santiago A, Villalobos I, Eiermann W, Pienkowski T, Martin M, Robert N, Crown J, Nuciforo P, Bee V, Mackey J, Slamon DJ, Press MF. PTEN Loss Is Associated with Worse Outcome in HER2-Amplified Breast Cancer Patients but Is Not Associated with Trastuzumab Resistance. Clin Cancer Res. 2015 May 1;21(9):2065-74. doi: 10.1158/1078-0432.CCR-14-2993. Epub 2015 Feb 3.
- Derived from this study: PubMed 40838872Blasco A, Lopez-Tarruella S, Urruticoechea A, Carrasco E, Spera G, Martin M, Bermejo B, Chap L, Ruiz-Borrego M, Crown J, Garcia-Saenz JA, Chan A, Guerrero-Zotano A, Semiglazov V, Calvo L, Pienkowski T, Herranz J, Slamon D. Intermediate endpoints as surrogates for long-term outcomes in breast cancer adjuvant chemotherapy trials. Oncologist. 2025 Sep 1;30(9):oyaf263. doi: 10.1093/oncolo/oyaf263.
- Derived from this study: PubMed 40207789Garcia-Saenz JA, Spera G, Pollan M, Bermejo B, Ruiz-Borrego M, Chan A, Martin M, Guerrero-Zotano A, Calvo L, Rodriguez-Lescure A, Marin M, Chap L, Crown J, Pienkowski T, Bee V, Casas M, Polonio O, Bezares S, Slamon D. Body mass index as a predictive factor for efficacy of adjuvant taxane-based chemotherapy in early-stage breast cancer patients: A pooled analysis from adjuvant GEICAM Spanish Breast Cancer Group and TRIO Translational Research in Oncology Group studies. Int J Cancer. 2025 Aug 15;157(4):709-721. doi: 10.1002/ijc.35432. Epub 2025 Apr 10.
- Derived from this study: PubMed 27573653Press MF, Sauter G, Buyse M, Fourmanoir H, Quinaux E, Tsao-Wei DD, Eiermann W, Robert N, Pienkowski T, Crown J, Martin M, Valero V, Mackey JR, Bee V, Ma Y, Villalobos I, Campeau A, Mirlacher M, Lindsay MA, Slamon DJ. HER2 Gene Amplification Testing by Fluorescent In Situ Hybridization (FISH): Comparison of the ASCO-College of American Pathologists Guidelines With FISH Scores Used for Enrollment in Breast Cancer International Research Group Clinical Trials. J Clin Oncol. 2016 Oct 10;34(29):3518-3528. doi: 10.1200/JCO.2016.66.6693.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
AUSSEL Jean Philippe study director
Sanofi
42 sites in 42 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Doxorubicin, Cyclophosphamide and Docetaxel in people with Breast Neoplasms, run by Sanofi at 42 sites in 42 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 42 sites in United States, Argentina, Australia, Austria, Belgium and 37 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Disease Free Survival at 5 Years (time frame: From randomization until relapse or death or up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00021255, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2016.