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

Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT00021255
Collaborator
Cancer International Research Group (CIRG) (Other)
3,222
Enrollment
42
Locations
3
Arms
164
Duration (Months)
76.7
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief 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, 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 or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
3222 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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
Study Start Date :
Apr 1, 2001
Actual Primary Completion Date :
Dec 1, 2014
Actual Study Completion Date :
Dec 1, 2014

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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 Names:
  • Taxotere

    • Drug: Herceptin
    Other Names:
  • 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 Names:
  • Taxotere

    • Drug: Herceptin
    Other Names:
  • Trastuzumab

    • Drug: Carboplatin

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Disease Free Survival at 5 Years [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.

    Secondary Outcome Measures

    1. Percentage of Participants With Disease Free Survival at 10 Years [From randomization until relapse or death or up to 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.

    2. Overall Survival- Percentage of Participants Who Survived at 10 Years [From randomization until death or up to 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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)

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

    2. 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.

    3. 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

    Locations

    Site City State Country Postal Code
    1 Sanofi-Aventis Administrative Office Bridgewater New Jersey United States 08807
    2 Sanofi-Aventis Administrative Office Buenos Aires Argentina
    3 Sanofi-Aventis Administrative Office Macquarie Park Australia
    4 Sanofi-Aventis Administrative Office Vienna Austria
    5 Sanofi-Aventis Administrative Office Diegem Belgium
    6 Sanofi-Aventis Administrative Office Sarajevo Bosnia and Herzegovina
    7 Sanofi-Aventis Administrative Office Sao Paulo Brazil
    8 Sanofi-Aventis Administrative Office Vazrjdane Region Bulgaria
    9 Sanofi-Aventis Administrative Office Québec Canada
    10 Sanofi-Aventis Administrative Office Bogota Colombia
    11 Sanofi-Aventis Administrative Office Zagreb Croatia
    12 Sanofi-Aventis Administrative Office Praha Czech Republic
    13 Sanofi-Aventis Administrative Office Cairo Egypt
    14 Sanofi-Aventis Administrative Office Tallin Estonia
    15 Sanofi-Aventis Administrative Office Paris France
    16 Sanofi-Aventis Administrative Office Frankfurt Germany
    17 Sanofi-Aventis Administrative Office Kallithea Greece
    18 Sanofi-Aventis Administrative Office Hong Kong Hong Kong
    19 Sanofi-Aventis Administrative Office Budapest Hungary
    20 Sanofi-Aventis Administrative Office Mumbai India
    21 Sanofi-Aventis Administrative Office Dublin Ireland
    22 Sanofi-Aventis Administrative Office Natanya Israel
    23 Sanofi-Aventis Administrative Office Milan Italy
    24 Sanofi-Aventis Administrative Office Seoul Korea, Republic of
    25 Sanofi-Aventis Administrative Office Beirut Lebanon
    26 Sanofi-Aventis Administrative Office Col. Coyoacan Mexico
    27 Sanofi-Aventis Administrative Office Macquarie Park New Zealand
    28 Sanofi-Aventis Administrative Office Warsaw Poland
    29 Sanofi-Aventis Administrative Office Bucuresti Romania
    30 Sanofi-Aventis Administrative Office Moscow Russian Federation
    31 Sanofi-Aventis Administrative Office Bratislava Slovakia
    32 Sanofi-Aventis Administrative Office Ljubljana Slovenia
    33 Sanofi-Aventis Administrative Office Gauteng South Africa
    34 Sanofi-Aventis Administrative Office Barcelona Spain
    35 Sanofi-Aventis Administrative Office Bromma Sweden
    36 Sanofi-Aventis Administrative Office Genève Switzerland
    37 Sanofi-Aventis Administrative Office Taipei Taiwan
    38 Sanofi-Aventis Administrative Office Megrine Tunisia
    39 Sanofi-Aventis Administrative Office Istanbul Turkey
    40 Sanofi-Aventis Administrative Office Guildford Surrey United Kingdom
    41 Sanofi-Aventis Administrative Office Montevideo Uruguay
    42 Sanofi-Aventis Administrative Office Caracas Venezuela

    Sponsors and Collaborators

    • Sanofi
    • Cancer International Research Group (CIRG)

    Investigators

    • Study Director: AUSSEL Jean Philippe, Sanofi

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT00021255
    Other Study ID Numbers:
    • TAX_GMA_302
    • BCIRG 006
    • NCT00768092
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Nov 15, 2016
    Last Verified:
    Sep 1, 2016
    Additional relevant MeSH terms:
    Breast Neoplasms
    Cyclophosphamide
    Carboplatin
    Docetaxel
    Doxorubicin
    Trastuzumab

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 433 centers in 43 countries. A total of 3222 participants randomized between 05 April 2001 and 30 March 2004. Participants stratified according to institution, nodal status(negative, positive 1-3 nodes, positive 4 or more nodes) and hormonal receptor status (estrogen and/or progesterone receptor positive versus negative).
    Pre-assignment Detail Participants were randomized in 1:1:1 ratio to receive adjuvant therapy with either AC→ T, AC→ TH or TCH. During the course of the study, some participants received treatment different from the arm in which they were randomized. The safety analyses was conducted as per the treatment received.
    Arm/Group Title Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T) AC Followed by Docetaxel + Herceptin (AC→TH) Docetaxel + Carboplatin + Herceptin (TCH)
    Arm/Group Description 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. 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. 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.
    Period Title: Overall Study
    STARTED 1073 1074 1075
    Treated 1045 1072 1057
    Safety Population 1018 1100 1056
    COMPLETED 952 804 926
    NOT COMPLETED 121 270 149

    Baseline Characteristics

    Arm/Group Title Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T) AC Followed by Docetaxel + Herceptin (AC→TH) Docetaxel + Carboplatin + Herceptin (TCH) Total
    Arm/Group Description 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 followed by docetaxel 100 mg/m² IV infusion every 3 weeks for another 4 cycles. 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. 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. Total of all reporting groups
    Overall Participants 1073 1074 1075 3222
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    48.8
    (9.7)
    48.7
    (9.7)
    48.6
    (9.9)
    48.7
    (9.8)
    Sex: Female, Male (Count of Participants)
    Female
    1073
    100%
    1074
    100%
    1075
    100%
    3222
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Disease Free Survival at 5 Years
    Description 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.
    Time Frame From randomization until relapse or death or up to 5 years

    Outcome Measure Data

    Analysis Population Description
    ITT population.
    Arm/Group Title Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T) AC Followed by Docetaxel + Herceptin (AC→TH) Docetaxel + Carboplatin + Herceptin (TCH)
    Arm/Group Description 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 followed by docetaxel 100 mg/m² IV infusion every 3 weeks for another 4 cycles. 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. 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.
    Measure Participants 1073 1074 1075
    Number (95% Confidence Interval) [percentage of participants]
    75.5
    7%
    83.2
    7.7%
    81.0
    7.5%
    2. Secondary Outcome
    Title Percentage of Participants With Disease Free Survival at 10 Years
    Description 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.
    Time Frame From randomization until relapse or death or up to 10 years

    Outcome Measure Data

    Analysis Population Description
    ITT population.
    Arm/Group Title Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T) AC Followed by Docetaxel + Herceptin (AC→TH) Docetaxel + Carboplatin + Herceptin (TCH)
    Arm/Group Description 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 followed by docetaxel 100 mg/m² IV infusion every 3 weeks for another 4 cycles. 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. 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.
    Measure Participants 1073 1074 1075
    Number (95% Confidence Interval) [percentage of participants]
    67.2
    6.3%
    73.4
    6.8%
    72.3
    6.7%
    3. Secondary Outcome
    Title Overall Survival- Percentage of Participants Who Survived at 10 Years
    Description 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.
    Time Frame From randomization until death or up to 10 years

    Outcome Measure Data

    Analysis Population Description
    ITT population.
    Arm/Group Title Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T) AC Followed by Docetaxel + Herceptin (AC→TH) Docetaxel + Carboplatin + Herceptin (TCH)
    Arm/Group Description 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 followed by docetaxel 100 mg/m² IV infusion every 3 weeks for another 4 cycles. 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. 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.
    Measure Participants 1073 1074 1075
    Number (95% Confidence Interval) [percentage of particpants]
    78.9
    86.0
    83.4

    Adverse Events

    Time Frame All Adverse Events (AE) were collected from the time the participant started treatment with study drug until 30 days after the last infusion of study treatment (chemotherapy or Herceptin).
    Adverse Event Reporting Description Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (from the first infusion of study drug until 30 days after the last infusion of study drug). Safety population included all treated participants. Source vocabulary used to define AE term: Pooled NCI-CTC version 2.0 and COSTART version 5.0
    Arm/Group Title Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T) AC Followed by Docetaxel + Herceptin (AC→TH) Docetaxel + Carboplatin + Herceptin (TCH)
    Arm/Group Description 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 followed by docetaxel 100 mg/m² IV infusion every 3 weeks for another 4 cycles. 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. 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.
    All Cause Mortality
    Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T) AC Followed by Docetaxel + Herceptin (AC→TH) Docetaxel + Carboplatin + Herceptin (TCH)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T) AC Followed by Docetaxel + Herceptin (AC→TH) Docetaxel + Carboplatin + Herceptin (TCH)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 218/1018 (21.4%) 298/1100 (27.1%) 283/1056 (26.8%)
    Blood and lymphatic system disorders
    ANEMIA 1/1018 (0.1%) 8/1100 (0.7%) 9/1056 (0.9%)
    LEUKOPENIA 21/1018 (2.1%) 23/1100 (2.1%) 20/1056 (1.9%)
    LYMPHEDEMA 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    PANCYTOPENIA 1/1018 (0.1%) 1/1100 (0.1%) 2/1056 (0.2%)
    THROMBOCYTOPENIA 0/1018 (0%) 1/1100 (0.1%) 3/1056 (0.3%)
    Cardiac disorders
    ANGINA PECTORIS 0/1018 (0%) 1/1100 (0.1%) 1/1056 (0.1%)
    AORTIC STENOSIS 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    ARRHYTHMIA 2/1018 (0.2%) 3/1100 (0.3%) 3/1056 (0.3%)
    ARTERIAL ANOMALY 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    AV BLOCK 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    CARDIOMYOPATHY 0/1018 (0%) 2/1100 (0.2%) 1/1056 (0.1%)
    CARDIOVASCULAR DISORDER 2/1018 (0.2%) 0/1100 (0%) 0/1056 (0%)
    CAROTID OCCLUSION 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    CEREBROVASCULAR ACCIDENT 0/1018 (0%) 1/1100 (0.1%) 3/1056 (0.3%)
    DEEP THROMBOPHLEBITIS 6/1018 (0.6%) 13/1100 (1.2%) 15/1056 (1.4%)
    ELECTROCARDIOGRAM ABNORMAL 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    HEART ARREST 0/1018 (0%) 2/1100 (0.2%) 1/1056 (0.1%)
    HEART FAILURE 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    HEMORRHAGE 0/1018 (0%) 2/1100 (0.2%) 2/1056 (0.2%)
    HYPERTENSION 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    HYPOTENSION 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    LEFT HEART FAILURE 8/1018 (0.8%) 25/1100 (2.3%) 2/1056 (0.2%)
    MYOCARDIAL ISCHEMIA 0/1018 (0%) 5/1100 (0.5%) 4/1056 (0.4%)
    MYOCARDITIS 1/1018 (0.1%) 0/1100 (0%) 0/1056 (0%)
    PALPITATION 0/1018 (0%) 3/1100 (0.3%) 1/1056 (0.1%)
    PERICARDIAL EFFUSION 1/1018 (0.1%) 0/1100 (0%) 0/1056 (0%)
    PHLEBITIS 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    POSTURAL HYPOTENSION 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    SYNCOPE 1/1018 (0.1%) 4/1100 (0.4%) 1/1056 (0.1%)
    TACHYCARDIA 2/1018 (0.2%) 0/1100 (0%) 2/1056 (0.2%)
    VASCULITIS 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    VENTRICULAR ARRHYTHMIA 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    Endocrine disorders
    THYROID DISORDER 1/1018 (0.1%) 0/1100 (0%) 0/1056 (0%)
    Gastrointestinal disorders
    ANOREXIA 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    CHOLECYSTITIS 2/1018 (0.2%) 0/1100 (0%) 1/1056 (0.1%)
    CHOLELITHIASIS 0/1018 (0%) 2/1100 (0.2%) 1/1056 (0.1%)
    COLITIS 0/1018 (0%) 1/1100 (0.1%) 4/1056 (0.4%)
    CONSTIPATION 1/1018 (0.1%) 0/1100 (0%) 1/1056 (0.1%)
    DIARRHEA 2/1018 (0.2%) 10/1100 (0.9%) 11/1056 (1%)
    DYSPHAGIA 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    ESOPHAGITIS 1/1018 (0.1%) 0/1100 (0%) 0/1056 (0%)
    GASTRITIS 1/1018 (0.1%) 1/1100 (0.1%) 0/1056 (0%)
    GASTROENTERITIS 1/1018 (0.1%) 2/1100 (0.2%) 3/1056 (0.3%)
    GASTROINTESTINAL HEMORRHAGE 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    HEMATEMESIS 0/1018 (0%) 1/1100 (0.1%) 1/1056 (0.1%)
    INTESTINAL PERFORATION 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    MELENA 1/1018 (0.1%) 1/1100 (0.1%) 0/1056 (0%)
    NAUSEA 3/1018 (0.3%) 7/1100 (0.6%) 3/1056 (0.3%)
    PERFORATED STOMACH ULCER 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    PROCTITIS 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    RECTAL HEMORRHAGE 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    STOMACH ULCER 0/1018 (0%) 0/1100 (0%) 2/1056 (0.2%)
    STOMATITIS 7/1018 (0.7%) 4/1100 (0.4%) 1/1056 (0.1%)
    VOMITING 12/1018 (1.2%) 16/1100 (1.5%) 11/1056 (1%)
    General disorders
    ABDOMINAL PAIN 2/1018 (0.2%) 3/1100 (0.3%) 2/1056 (0.2%)
    ABSCESS 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    ACCIDENTAL INJURY 0/1018 (0%) 3/1100 (0.3%) 3/1056 (0.3%)
    AGGRAVATION REACTION 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    ALLERGIC REACTION 2/1018 (0.2%) 7/1100 (0.6%) 5/1056 (0.5%)
    ASTHENIA 4/1018 (0.4%) 3/1100 (0.3%) 6/1056 (0.6%)
    BACK PAIN 1/1018 (0.1%) 3/1100 (0.3%) 0/1056 (0%)
    CELLULITIS 7/1018 (0.7%) 7/1100 (0.6%) 11/1056 (1%)
    CHEST PAIN 5/1018 (0.5%) 7/1100 (0.6%) 6/1056 (0.6%)
    CHILLS 1/1018 (0.1%) 0/1100 (0%) 0/1056 (0%)
    CYST 0/1018 (0%) 0/1100 (0%) 4/1056 (0.4%)
    FEVER 85/1018 (8.3%) 109/1100 (9.9%) 86/1056 (8.1%)
    HEADACHE 1/1018 (0.1%) 0/1100 (0%) 1/1056 (0.1%)
    HYPOTHERMIA 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    IMMUNE SYSTEM DISORDER 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    INFECTION 68/1018 (6.7%) 85/1100 (7.7%) 85/1056 (8%)
    INJECTION SITE PAIN 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    MUCOUS MEMBRANE DISORDER 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    PAIN 1/1018 (0.1%) 1/1100 (0.1%) 0/1056 (0%)
    PERITONITIS 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    PHOTOSENSITIVITY REACTION 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    RADIATION INJURY 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    REACTION UNEVALUABLE 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    SEPSIS 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    DEAFNESS 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    EAR PAIN 1/1018 (0.1%) 0/1100 (0%) 0/1056 (0%)
    OTITIS MEDIA 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    VESTIBULAR DISORDER 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    Metabolism and nutrition disorders
    ACIDOSIS 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    DEHYDRATION 1/1018 (0.1%) 5/1100 (0.5%) 5/1056 (0.5%)
    EDEMA 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    ENZYMATIC ABNORMALITY 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    GENERALIZED EDEMA 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    HYPERGLYCEMIA 1/1018 (0.1%) 0/1100 (0%) 1/1056 (0.1%)
    HYPOKALEMIA 0/1018 (0%) 0/1100 (0%) 2/1056 (0.2%)
    HYPOMAGNESEMIA 0/1018 (0%) 0/1100 (0%) 3/1056 (0.3%)
    HYPONATREMIA 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    HYPOVOLEMIA 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    PERIPHERAL EDEMA 1/1018 (0.1%) 1/1100 (0.1%) 1/1056 (0.1%)
    SGOT INCREASED 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 1/1018 (0.1%) 1/1100 (0.1%) 1/1056 (0.1%)
    ARTHRITIS 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    BONE PAIN 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    JOINT DISORDER 0/1018 (0%) 1/1100 (0.1%) 1/1056 (0.1%)
    MYALGIA 1/1018 (0.1%) 1/1100 (0.1%) 1/1056 (0.1%)
    Nervous system disorders
    ANXIETY 1/1018 (0.1%) 1/1100 (0.1%) 0/1056 (0%)
    CEREBRAL INFARCT 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    COMA 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    CONFUSION 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    CONVULSION 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    DEPRESSION 0/1018 (0%) 5/1100 (0.5%) 3/1056 (0.3%)
    DIZZINESS 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    EMOTIONAL LABILITY 0/1018 (0%) 2/1100 (0.2%) 0/1056 (0%)
    GRAND MAL CONVULSION 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    MENINGITIS 1/1018 (0.1%) 0/1100 (0%) 0/1056 (0%)
    NEUROPATHY 3/1018 (0.3%) 3/1100 (0.3%) 4/1056 (0.4%)
    TRISMUS 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    VERTIGO 0/1018 (0%) 0/1100 (0%) 2/1056 (0.2%)
    Renal and urinary disorders
    BREAST NEOPLASM 0/1018 (0%) 1/1100 (0.1%) 1/1056 (0.1%)
    CYSTITIS 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    ENDOMETRIAL CARCINOMA 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    ENDOMETRIAL DISORDER 1/1018 (0.1%) 0/1100 (0%) 0/1056 (0%)
    HEMATURIA 0/1018 (0%) 0/1100 (0%) 2/1056 (0.2%)
    KIDNEY FAILURE 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    KIDNEY FUNCTION ABNORMAL 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    MENSTRUAL DISORDER 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    TOXIC NEPHROPATHY 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    URINARY TRACT DISORDER 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    URINARY TRACT INFECTION 0/1018 (0%) 2/1100 (0.2%) 1/1056 (0.1%)
    VAGINITIS 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    Respiratory, thoracic and mediastinal disorders
    APNEA 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    ASTHMA 0/1018 (0%) 1/1100 (0.1%) 2/1056 (0.2%)
    BRONCHIECTASIS 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    DYSPNEA 0/1018 (0%) 1/1100 (0.1%) 3/1056 (0.3%)
    LUNG DISORDER 0/1018 (0%) 2/1100 (0.2%) 0/1056 (0%)
    LUNG EDEMA 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    LUNG FIBROSIS 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    PHARYNGITIS 1/1018 (0.1%) 0/1100 (0%) 2/1056 (0.2%)
    PLEURAL EFFUSION 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    PNEUMONIA 4/1018 (0.4%) 4/1100 (0.4%) 3/1056 (0.3%)
    PNEUMOTHORAX 0/1018 (0%) 3/1100 (0.3%) 0/1056 (0%)
    RHINITIS 1/1018 (0.1%) 2/1100 (0.2%) 0/1056 (0%)
    SINUSITIS 0/1018 (0%) 1/1100 (0.1%) 1/1056 (0.1%)
    Skin and subcutaneous tissue disorders
    ACNE 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    APPLICATION SITE REACTION 1/1018 (0.1%) 1/1100 (0.1%) 0/1056 (0%)
    EXFOLIATIVE DERMATITIS 3/1018 (0.3%) 1/1100 (0.1%) 0/1056 (0%)
    FUNGAL DERMATITIS 0/1018 (0%) 0/1100 (0%) 1/1056 (0.1%)
    MACULOPAPULAR RASH 4/1018 (0.4%) 1/1100 (0.1%) 1/1056 (0.1%)
    NAIL DISORDER 1/1018 (0.1%) 0/1100 (0%) 0/1056 (0%)
    RASH 0/1018 (0%) 0/1100 (0%) 3/1056 (0.3%)
    SKIN BENIGN NEOPLASM 0/1018 (0%) 1/1100 (0.1%) 0/1056 (0%)
    Other (Not Including Serious) Adverse Events
    Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T) AC Followed by Docetaxel + Herceptin (AC→TH) Docetaxel + Carboplatin + Herceptin (TCH)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1017/1018 (99.9%) 1100/1100 (100%) 1052/1056 (99.6%)
    Blood and lymphatic system disorders
    LYMPHEDEMA 81/1018 (8%) 94/1100 (8.5%) 107/1056 (10.1%)
    Cardiac disorders
    HYPERTENSION 40/1018 (3.9%) 72/1100 (6.5%) 78/1056 (7.4%)
    LEFT HEART FAILURE 30/1018 (2.9%) 71/1100 (6.5%) 31/1056 (2.9%)
    PALPITATION 69/1018 (6.8%) 94/1100 (8.5%) 95/1056 (9%)
    TACHYCARDIA 50/1018 (4.9%) 62/1100 (5.6%) 67/1056 (6.3%)
    Gastrointestinal disorders
    ANOREXIA 230/1018 (22.6%) 238/1100 (21.6%) 252/1056 (23.9%)
    CONSTIPATION 383/1018 (37.6%) 403/1100 (36.6%) 351/1056 (33.2%)
    DIARRHEA 439/1018 (43.1%) 555/1100 (50.5%) 658/1056 (62.3%)
    DYSPEPSIA 204/1018 (20%) 273/1100 (24.8%) 263/1056 (24.9%)
    NAUSEA 890/1018 (87.4%) 967/1100 (87.9%) 863/1056 (81.7%)
    STOMATITIS 660/1018 (64.8%) 735/1100 (66.8%) 564/1056 (53.4%)
    VOMITING 563/1018 (55.3%) 628/1100 (57.1%) 428/1056 (40.5%)
    General disorders
    ABDOMINAL PAIN 179/1018 (17.6%) 220/1100 (20%) 240/1056 (22.7%)
    ALLERGIC REACTION 100/1018 (9.8%) 137/1100 (12.5%) 153/1056 (14.5%)
    ASTHENIA 838/1018 (82.3%) 925/1100 (84.1%) 878/1056 (83.1%)
    BACK PAIN 82/1018 (8.1%) 132/1100 (12%) 96/1056 (9.1%)
    CHEST PAIN 73/1018 (7.2%) 103/1100 (9.4%) 91/1056 (8.6%)
    CHILLS 58/1018 (5.7%) 88/1100 (8%) 78/1056 (7.4%)
    FEVER 162/1018 (15.9%) 206/1100 (18.7%) 145/1056 (13.7%)
    HEADACHE 301/1018 (29.6%) 323/1100 (29.4%) 306/1056 (29%)
    INFECTION 350/1018 (34.4%) 445/1100 (40.5%) 327/1056 (31%)
    INJECTION SITE REACTION 66/1018 (6.5%) 70/1100 (6.4%) 84/1056 (8%)
    PAIN 222/1018 (21.8%) 268/1100 (24.4%) 217/1056 (20.5%)
    AMBLYOPIA 34/1018 (3.3%) 52/1100 (4.7%) 55/1056 (5.2%)
    CONJUNCTIVITIS 111/1018 (10.9%) 122/1100 (11.1%) 45/1056 (4.3%)
    DRY EYES 41/1018 (4%) 56/1100 (5.1%) 30/1056 (2.8%)
    LACRIMATION DISORDER 210/1018 (20.6%) 264/1100 (24%) 124/1056 (11.7%)
    TASTE PERVERSION 291/1018 (28.6%) 312/1100 (28.4%) 320/1056 (30.3%)
    Metabolism and nutrition disorders
    HYPERGLYCEMIA 77/1018 (7.6%) 85/1100 (7.7%) 79/1056 (7.5%)
    PERIPHERAL EDEMA 339/1018 (33.3%) 405/1100 (36.8%) 347/1056 (32.9%)
    WEIGHT GAIN 197/1018 (19.4%) 262/1100 (23.8%) 254/1056 (24.1%)
    WEIGHT LOSS 81/1018 (8%) 100/1100 (9.1%) 69/1056 (6.5%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 439/1018 (43.1%) 515/1100 (46.8%) 335/1056 (31.7%)
    BONE PAIN 187/1018 (18.4%) 235/1100 (21.4%) 144/1056 (13.6%)
    MYALGIA 541/1018 (53.1%) 614/1100 (55.8%) 415/1056 (39.3%)
    Nervous system disorders
    ANXIETY 86/1018 (8.4%) 78/1100 (7.1%) 70/1056 (6.6%)
    DEPRESSION 106/1018 (10.4%) 139/1100 (12.6%) 119/1056 (11.3%)
    DIZZINESS 112/1018 (11%) 154/1100 (14%) 130/1056 (12.3%)
    DRY MOUTH 87/1018 (8.5%) 55/1100 (5%) 37/1056 (3.5%)
    EMOTIONAL LABILITY 56/1018 (5.5%) 65/1100 (5.9%) 41/1056 (3.9%)
    INSOMNIA 226/1018 (22.2%) 288/1100 (26.2%) 252/1056 (23.9%)
    NEUROPATHY 514/1018 (50.5%) 569/1100 (51.7%) 406/1056 (38.4%)
    VASODILATATION 364/1018 (35.8%) 416/1100 (37.8%) 384/1056 (36.4%)
    Renal and urinary disorders
    BREAST PAIN 53/1018 (5.2%) 59/1100 (5.4%) 62/1056 (5.9%)
    DYSURIA 24/1018 (2.4%) 51/1100 (4.6%) 58/1056 (5.5%)
    MENSTRUAL DISORDER 368/1018 (36.1%) 356/1100 (32.4%) 384/1056 (36.4%)
    Respiratory, thoracic and mediastinal disorders
    COUGH INCREASED 187/1018 (18.4%) 205/1100 (18.6%) 147/1056 (13.9%)
    DYSPNEA 227/1018 (22.3%) 270/1100 (24.5%) 229/1056 (21.7%)
    EPISTAXIS 60/1018 (5.9%) 143/1100 (13%) 170/1056 (16.1%)
    PHARYNGITIS 74/1018 (7.3%) 94/1100 (8.5%) 60/1056 (5.7%)
    RHINITIS 175/1018 (17.2%) 277/1100 (25.2%) 193/1056 (18.3%)
    Skin and subcutaneous tissue disorders
    ALOPECIA 1003/1018 (98.5%) 1083/1100 (98.5%) 1018/1056 (96.4%)
    DRY SKIN 76/1018 (7.5%) 101/1100 (9.2%) 61/1056 (5.8%)
    EXFOLIATIVE DERMATITIS 87/1018 (8.5%) 87/1100 (7.9%) 32/1056 (3%)
    MACULOPAPULAR RASH 275/1018 (27%) 354/1100 (32.2%) 330/1056 (31.3%)
    NAIL DISORDER 507/1018 (49.8%) 484/1100 (44%) 303/1056 (28.7%)
    PRURITUS 38/1018 (3.7%) 50/1100 (4.5%) 66/1056 (6.3%)
    RASH 238/1018 (23.4%) 279/1100 (25.4%) 313/1056 (29.6%)
    SKIN DISCOLORATION 65/1018 (6.4%) 67/1100 (6.1%) 50/1056 (4.7%)
    SWEATING 67/1018 (6.6%) 67/1100 (6.1%) 73/1056 (6.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.

    Results Point of Contact

    Name/Title Trial Transparency Team
    Organization Sanofi
    Phone
    Email Contact-US@sanofi.com
    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT00021255
    Other Study ID Numbers:
    • TAX_GMA_302
    • BCIRG 006
    • NCT00768092
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Nov 15, 2016
    Last Verified:
    Sep 1, 2016