Docetaxel in Breast Cancer

NCT ID: NCT00312208

Last Updated: 2013-12-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 3299 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-11-30
• Study Completion Date: 2013-10-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

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

Group Type: EXPERIMENTAL

Docetaxel,doxorubicin, cyclophosphamide

Intervention Type: 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.

2

Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)

Group Type: EXPERIMENTAL

docetaxel, doxorubicin, cyclophosphamide

Intervention Type: 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.

Interventions

docetaxel, doxorubicin, cyclophosphamide

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.

Intervention Type: DRUG

Docetaxel,doxorubicin, cyclophosphamide

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• Alkaline phosphatase < or = 5 UNL
• Patients 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:

• Creatinine < or = 175 µmol/L (2 mg/dL);
• If limit reached, the calculated creatinine clearance should be > or = 60mL/min.
• Complete staging work-up within 3 months prior to registration. All patients will have contralateral mammography, chest X-ray (Posteroanterior and lateral) and/or CT scan and/or MRI (Magnetic Resonance Imaging), abdominal ultrasound and/or CT scan (computerized tomography) and/or MRI, and bone scan. In case of positive bone scan, bone X-ray is mandatory to rule out the possibility of non-metastatic hot spots. 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.

Exclusion Criteria

• 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
• other cancer curatively treated and with no evidence of disease for at least 10 years
• 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 (< 20 mg methylprednisolone or equivalent).
• 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.
• Current therapy with any hormonal agent such as raloxifene, tamoxifen or other selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention. Patients must have discontinued these agents prior to randomization.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Cancer International Research Group (CIRG)

OTHER

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Philippe AUSSEL

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis

Bridgewater, New Jersey, United States

Sanofi-Aventis

Buenos Aires, , Argentina

Sanofi-Aventis

Macquarie Park, , Australia

Sanofi-Aventis

Brussels, , Belgium

Sanofi-Aventis

Sarajevo, , Bosnia and Herzegovina

Sanofi-Aventis

São Paulo, , Brazil

Sanofi-Aventis

Sofia, , Bulgaria

Sanofi-Aventis

Laval, , Canada

Sanofi-Aventis

Shanghai, , China

Sanofi-Aventis

Bogotá, , Colombia

Sanofi-Aventis

Zagreb, , Croatia

Sanofi-Aventis

Nicosia, , Cyprus

Sanofi-Aventis

Prague, , Czechia

Sanofi-Aventis

Cairo, , Egypt

Sanofi-Aventis

Tallinn, , Estonia

Sanofi-Aventis

Paris, , France

Sanofi-Aventis

Berlin, , Germany

Sanofi-Aventis

Kallithea, , Greece

Sanofi-Aventis

Hong Kong, , Hong Kong

Sanofi-Aventis

Budapest, , Hungary

Sanofi-Aventis

Dublin, , Ireland

Sanofi-Aventis

Netanya, , Israel

Sanofi-Aventis

Beirut, , Lebanon

Sanofi-Aventis

México, , Mexico

Sanofi-aventis

Auckland, , New Zealand

Sanofi-Aventis

Warsaw, , Poland

Sanofi-Aventis

Porto Salvo, , Portugal

Sanofi-Aventis

Bucharest, , Romania

Sanofi-Aventis

Moscow, , Russia

Sanofi-Aventis

Jeddah, , Saudi Arabia

Sanofi-Aventis

Ljubljana, , Slovenia

Sanofi-Aventis

Midrand, , South Africa

Sanofi-Aventis

Seoul, , South Korea

Sanofi-Aventis

Barcelona, , Spain

Sanofi-Aventis

Taipei, , Taiwan

Sanofi-Aventis

Montevideo, , Uruguay

Sanofi-Aventis

Caracas, , Venezuela

Countries

United States; Argentina; Australia; Belgium; Bosnia and Herzegovina; Brazil; Bulgaria; Canada; China; Colombia; Croatia; Cyprus; Czechia; Egypt; Estonia; France; Germany; Greece; Hong Kong; Hungary; Ireland; Israel; Lebanon; Mexico; New Zealand; Poland; Portugal; Romania; Russia; Saudi Arabia; Slovenia; South Africa; South Korea; Spain; Taiwan; Uruguay; Venezuela

References

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.

Reference Type: DERIVED

PMID: 40838872 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27573653 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26940688 (View on PubMed)

Other Identifiers

BCIRG 005

Identifier Type: -

Identifier Source: secondary_id

TAX_GMA_301

Identifier Type: -

Identifier Source: org_study_id