Docetaxel in Breast Cancer

NCT00312208 | Completed Phase 3 Results

• 2 other identifiers: TAX_GMA_301BCIRG 005
• Study Type: interventional
• Target: 3,299
• Locations: 36 countries
• Sites: 36

Brief Summary

Primary objective :

• To compare disease-free survival after treatment with docetaxel in combination with doxorubicin and cyclophosphamide to doxorubicin and cyclophosphamide followed by docetaxel in operable adjuvant breast cancer HER2neu negative patients with positive axillary lymph nodes. Secondary objectives :
• To compare toxicity and quality of life between the 2 above-mentioned arms.
• To evaluate pathologic and molecular markers for predicting efficacy.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Local, Regional or Metastatic Relapse, or Second Primary Cancer, or Death From Any Cause (Disease-Free Survival)

  The primary event is the local, regional or metastatic relapse or the date of second primary cancer or death from any cause (whichever occurs first). The primary efficacy analysis is performed on the time from randomization to this primary event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.

  Median follow-up 65 months

Secondary Outcomes (1)

• Death From Any Cause (Overall Survival)

  Median follow-up of 65 months

Study Arms (2)

1

EXPERIMENTAL

Doxorubicin in combination with cyclophosphamide followed by docetaxel (AC -\> T)

Drug: Docetaxel,doxorubicin, cyclophosphamide

2

EXPERIMENTAL

Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)

Drug: docetaxel, doxorubicin, cyclophosphamide

Interventions

docetaxel, doxorubicin, cyclophosphamide DRUG

TAC x 6 : Docetaxel 75 mg/m² as 1 hour IV infusion on day 1 every 3 weeks in combination with doxorubicin 50 mg/m² as an IV bolus and cyclophosphamide 500 mg/m2 as IV on day 1 every 3 weeks. Sequence of administration is as follows: doxorubicin followed by cyclophosphamide followed by docetaxel.

2

Docetaxel,doxorubicin, cyclophosphamide DRUG

AC x 4: Doxorubicin 60 mg/m² as an IV bolus in combination with cyclophosphamide 600 mg/m² as IV followed by docetaxel 100 mg/m² as 1 hour IV infusion on day 1 every 3 weeks for 4 cycles.

1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven breast cancer. Interval between definitive surgery that includes axillary lymph node dissection and registration is less than or equal to 60 days. A central pathology review may be performed post randomization for confirmation of diagnosis and molecular studies.
• Definitive surgical treatment must be either mastectomy, or breast conserving surgery with axillary lymph node dissection 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 Ductal Carcinoma In Situ (DCIS). Lobular carcinoma in-situ does not count as a positive margin.
• Histologic examination of the tumor: Invasive adenocarcinoma with at least one axillary lymph node (pN1) showing evidence of tumor among a minimum of six resected lymph nodes.
• Tumor must show negative HER2 neu proto-oncogene overexpression by FISH (Fluorescence In Situ Hybridization). Confirmation of non overexpression will be centrally assessed by authorized BCIRG (Breast Cancer International Research Group) laboratories prior to randomization.
• Estrogen and/or progesterone receptor analysis performed on the primary tumor prior to randomization. Results must be known at the time of randomization.(Note: Patients whose tumor is estrogen receptor negative with progesterone receptor status unknown or undetermined, must have the progesterone receptor assayed in order to determine hormonal receptor status. Patients whose tumor is progesterone receptor negative with estrogen receptor status unknown or undetermined, must have the estrogen receptor assayed in order to determine hormonal receptor status).
• Karnofsky Performance status index \> 80%.
• Normal cardiac function must be confirmed by LVEF (Lef Ventricular Ejection Fraction) i.e. MUGA (Multi Gated Acquisition) scan or echocardiography and ECG within 3 months prior to registration. LVEF result must be above or equal to the lower limit of normal for the institution. The ECG results must be within normal limits or show no significant abnormalities.
• Laboratory requirements: (within 14 days prior to registration)
• Hematology:
• Neutrophils \> or = 2.0 x 10\^9/L
• Platelets \> or = 100 x 10\^9/L
• Hemoglobin \> or = 10 g/dL
• Hepatic function:
• Total bilirubin \< or = 1 UNL (Upper Normal Limit)
• ASAT (Aspartate Amino Transferase) and ALAT (Alanine Amino Transferase) \< or = 2.5 UNL

You may not qualify if:

• Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, genetherapy , 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 (chemotherapy and tamoxifen therapy) and must have negative urine or serum pregnancy test within 7 days prior to registration.
• Any T4 or N2 or known N3 or M1 breast cancer.
• Pre-existing motor or sensory neurotoxicity of a severity \> grade 2 by NCI-CTC (National Cancer Institute - Common Toxicity Criteria), version 2.0.
• Other serious illness or medical condition:
• congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias
• 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
• Past or current history of neoplasm other than breast carcinoma, except for:
• curatively treated non-melanoma skin cancer
• carcinoma in situ of the cervix

Sponsors & Collaborators

• Sanofi: lead
• Cancer International Research Group (CIRG): collaborator

Study Sites (37)

Sanofi-Aventis

Bridgewater, New Jersey, 08807, United States

Location

Sanofi-Aventis

Buenos Aires, Argentina

Location

Sanofi-Aventis

Macquarie Park, Australia

Location

Sanofi-Aventis

Brussels, Belgium

Location

Sanofi-Aventis

Sarajevo, Bosnia and Herzegovina

Location

Sanofi-Aventis

São Paulo, Brazil

Location

Sanofi-Aventis

Sofia, Bulgaria

Location

Sanofi-Aventis

Laval, Canada

Location

Sanofi-Aventis

Shanghai, China

Location

Sanofi-Aventis

Bogotá, Colombia

Location

Sanofi-Aventis

Zagreb, Croatia

Location

Sanofi-Aventis

Nicosia, Cyprus

Location

Sanofi-Aventis

Prague, Czechia

Location

Sanofi-Aventis

Cairo, Egypt

Location

Sanofi-Aventis

Tallinn, Estonia

Location

Sanofi-Aventis

Paris, France

Location

Sanofi-Aventis

Berlin, Germany

Location

Sanofi-Aventis

Kallithea, Greece

Location

Sanofi-Aventis

Hong Kong, Hong Kong

Location

Sanofi-Aventis

Budapest, Hungary

Location

Sanofi-Aventis

Dublin, Ireland

Location

Sanofi-Aventis

Netanya, Israel

Location

Sanofi-Aventis

Beirut, Lebanon

Location

Sanofi-Aventis

México, Mexico

Location

Sanofi-aventis

Auckland, New Zealand

Location

Sanofi-Aventis

Warsaw, Poland

Location

Sanofi-Aventis

Porto Salvo, Portugal

Location

Sanofi-Aventis

Bucharest, Romania

Location

Sanofi-Aventis

Moscow, Russia

Location

Sanofi-Aventis

Jeddah, Saudi Arabia

Location

Sanofi-Aventis

Ljubljana, Slovenia

Location

Sanofi-Aventis

Midrand, South Africa

Location

Sanofi-Aventis

Seoul, South Korea

Location

Sanofi-Aventis

Barcelona, Spain

Location

Sanofi-Aventis

Taipei, Taiwan

Location

Sanofi-Aventis

Montevideo, Uruguay

Location

Sanofi-Aventis

Caracas, Venezuela

Location

Related Publications (3)

• Blasco 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.

  PMID: 40838872 DERIVED

• Press 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.

  PMID: 27573653 DERIVED

• Mackey JR, Pienkowski T, Crown J, Sadeghi S, Martin M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press MF, Sauter G, Lindsay M, Houe V, Buyse M, Drevot P, Hitier S, Bensfia S, Eiermann W. Long-term outcomes after adjuvant treatment of sequential versus combination docetaxel with doxorubicin and cyclophosphamide in node-positive breast cancer: BCIRG-005 randomized trial. Ann Oncol. 2016 Jun;27(6):1041-1047. doi: 10.1093/annonc/mdw098. Epub 2016 Mar 2.

  PMID: 26940688 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; Doxorubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Medical Affairs study director
• Organization: sanofi-aventis

publicregistryGMA@sanofi-aventis.com

Study Officials

• Jean-Philippe AUSSEL

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2006
• First Posted: April 7, 2006
• Study Start: November 1, 2001
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2013
• Last Updated: December 30, 2013
• Results First Posted: February 17, 2010

Record last verified: 2013-12

Locations

SA (1); AU (1); AR (1); BE (1); TW (1); ES (1); ME (1); BU (1); ZA (1); PL (1); VE (1); KR (1); IL (1); HU (1); CA (1); CY (1); BO (1); DE (1); RO (1); CZ (1); CO (1); IE (1); US (1); NZ (1); SL (1); FR (1); CR (1); HK (1); RU (1); LE (1); PT (1); CN (1); GR (1); BR (1); EG (1); UR (1)