Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Cancer International Research Group (CIRG)
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00021255
First received: July 11, 2001
Last updated: September 26, 2016
Last verified: September 2016
  Purpose

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.

Condition Intervention Phase
Breast Neoplasms
Drug: Doxorubicin
Drug: Cyclophosphamide
Drug: Docetaxel
Drug: Herceptin
Drug: Carboplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percentage of Participants With Disease Free Survival at 5 Years [ Time Frame: From randomization until relapse or death or up to 5 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Disease Free Survival at 10 Years [ Time Frame: From randomization until relapse or death or up to 10 years ] [ Designated as safety issue: No ]
    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.

  • Overall Survival- Percentage of Participants Who Survived at 10 Years [ Time Frame: From randomization until death or up to 10 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 3222
Study Start Date: April 2001
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxorubicin+Cyclophosphamide (AC) followed by Docetaxel (AC→T)
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.
Drug: Doxorubicin Drug: Cyclophosphamide Drug: Docetaxel
Other Name: Taxotere
Experimental: AC followed by Docetaxel + Herceptin (AC→TH)
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.
Drug: Doxorubicin Drug: Cyclophosphamide Drug: Docetaxel
Other Name: Taxotere
Drug: Herceptin
Other Name: Trastuzumab
Experimental: Docetaxel + Carboplatin + Herceptin (TCH)
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.
Drug: Docetaxel
Other Name: Taxotere
Drug: Herceptin
Other Name: Trastuzumab
Drug: Carboplatin

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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.
  • 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)

    a) Hematology: i) Neutrophils ≥ 2.0 109/L ii) Platelets ≥ 100 109/L iii) Hemoglobin ≥ 10 g/Dl

    b) 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.

    c) 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.

Exclusion criteria:

  • 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.
  • 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:

    1. any documented myocardial infarction
    2. angina pectoris that required the use of antianginal medication
    3. any history of documented congestive heart failure
    4. Grade 3 or Grade 4 cardiac arrhythmia (NCI Common Terminology Criteria [CTC], version 2.0)
    5. clinically significant valvular heart disease
    6. 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;
    7. participants with poorly controlled hypertension i.e. diastolic greater than 100 mm/Hg. (Participants who were well controlled on medication were eligible for entry)
    8. 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:

    1. history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
    2. active uncontrolled infection
    3. active peptic ulcer, unstable diabetes mellitus
    4. 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:

    1. curatively treated non-melanoma skin cancer
    2. in situ carcinoma of the cervix
    3. other cancer curatively treated and with no evidence of disease for at least 10 years
    4. ipsilateral DCIS of the breast
    5. 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00021255

  Hide Study Locations
Locations
United States, New Jersey
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, United States, 08807
Argentina
Sanofi-Aventis Administrative Office
Buenos Aires, Argentina
Australia
Sanofi-Aventis Administrative Office
Macquarie Park, Australia
Austria
Sanofi-Aventis Administrative Office
Vienna, Austria
Belgium
Sanofi-Aventis Administrative Office
Diegem, Belgium
Bosnia and Herzegovina
Sanofi-Aventis Administrative Office
Sarajevo, Bosnia and Herzegovina
Brazil
Sanofi-Aventis Administrative Office
Sao Paulo, Brazil
Bulgaria
Sanofi-Aventis Administrative Office
Vazrjdane Region, Bulgaria
Canada
Sanofi-Aventis Administrative Office
Québec, Canada
Colombia
Sanofi-Aventis Administrative Office
Bogota, Colombia
Croatia
Sanofi-Aventis Administrative Office
Zagreb, Croatia
Czech Republic
Sanofi-Aventis Administrative Office
Praha, Czech Republic
Egypt
Sanofi-Aventis Administrative Office
Cairo, Egypt
Estonia
Sanofi-Aventis Administrative Office
Tallin, Estonia
France
Sanofi-Aventis Administrative Office
Paris, France
Germany
Sanofi-Aventis Administrative Office
Frankfurt, Germany
Greece
Sanofi-Aventis Administrative Office
Kallithea, Greece
Hong Kong
Sanofi-Aventis Administrative Office
Hong Kong, Hong Kong
Hungary
Sanofi-Aventis Administrative Office
Budapest, Hungary
India
Sanofi-Aventis Administrative Office
Mumbai, India
Ireland
Sanofi-Aventis Administrative Office
Dublin, Ireland
Israel
Sanofi-Aventis Administrative Office
Natanya, Israel
Italy
Sanofi-Aventis Administrative Office
Milan, Italy
Korea, Republic of
Sanofi-Aventis Administrative Office
Seoul, Korea, Republic of
Lebanon
Sanofi-Aventis Administrative Office
Beirut, Lebanon
Mexico
Sanofi-Aventis Administrative Office
Col. Coyoacan, Mexico
New Zealand
Sanofi-Aventis Administrative Office
Macquarie Park, New Zealand
Poland
Sanofi-Aventis Administrative Office
Warsaw, Poland
Romania
Sanofi-Aventis Administrative Office
Bucuresti, Romania
Russian Federation
Sanofi-Aventis Administrative Office
Moscow, Russian Federation
Slovakia
Sanofi-Aventis Administrative Office
Bratislava, Slovakia
Slovenia
Sanofi-Aventis Administrative Office
Ljubljana, Slovenia
South Africa
Sanofi-Aventis Administrative Office
Gauteng, South Africa
Spain
Sanofi-Aventis Administrative Office
Barcelona, Spain
Sweden
Sanofi-Aventis Administrative Office
Bromma, Sweden
Switzerland
Sanofi-Aventis Administrative Office
Genève, Switzerland
Taiwan
Sanofi-Aventis Administrative Office
Taipei, Taiwan
Tunisia
Sanofi-Aventis Administrative Office
Megrine, Tunisia
Turkey
Sanofi-Aventis Administrative Office
Istanbul, Turkey
United Kingdom
Sanofi-Aventis Administrative Office
Guildford Surrey, United Kingdom
Uruguay
Sanofi-Aventis Administrative Office
Montevideo, Uruguay
Venezuela
Sanofi-Aventis Administrative Office
Caracas, Venezuela
Sponsors and Collaborators
Sanofi
Cancer International Research Group (CIRG)
Investigators
Study Director: AUSSEL Jean Philippe Sanofi
  More Information

Publications:

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00021255     History of Changes
Obsolete Identifiers: NCT00768092
Other Study ID Numbers: TAX_GMA_302  BCIRG 006 
Study First Received: July 11, 2001
Results First Received: June 15, 2016
Last Updated: September 26, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Doxorubicin
Liposomal doxorubicin
Docetaxel
Cyclophosphamide
Carboplatin
Trastuzumab
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on December 02, 2016