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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cancer International Research Group
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00021255
First received: July 11, 2001
Last updated: July 29, 2014
Last verified: July 2014

July 11, 2001
July 29, 2014
March 2002
November 2014   (final data collection date for primary outcome measure)
Disease free survival [ Time Frame: calculated from the date of randomization up to the first date of local, regional, or distant relapse, second primary cancer (with the exception of curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix) ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00021255 on ClinicalTrials.gov Archive Site
Overall survival [ Time Frame: measured from the date of randomization up to the date of death of any cause. ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer
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 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 patients treated with these regimens.
  • Compare the toxic effects (including cardiac) of these regimens in these patients.
  • Compare quality of life of patients treated with these regimens.
  • Compare pathologic and molecular markers for predicting efficacy of these regimens in these patients.
  • For substudy: Compare peripheral levels of shed HER2-neu extracellular domain with fluorescence in situ hybridization in predicting outcome in patients treated with these regimens.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Neoplasms
  • Drug: doxorubicine, cyclophosphamide, docetaxel
    doxorubicine IV, cyclophosphamide IV, docetaxel IV
  • Drug: doxorubicine, cyclophosphamide, trastuzumab, docetaxel
    doxorubicine IV, cyclophosphamide IV, trastuzumab IV, docetaxel IV
  • Drug: trastuzumab, docetaxel, carboplatin
    trastuzumab IV, docetaxel IV, carboplatin IV
  • Experimental: 1
    Patients receive doxorubicin IV over 5-15 minutes and cyclophosphamide IV over 5-60 minutes on day 1 every 3 weeks for 4 courses. Beginning 3 weeks after the last course of doxorubicin and cyclophosphamide, patients receive docetaxel IV over 1 hour every 3 weeks for 4 courses.
    Intervention: Drug: doxorubicine, cyclophosphamide, docetaxel
  • Experimental: 2
    Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning 3 weeks after the last course of doxorubicin and cyclophosphamide, patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15. Patients also receive docetaxel IV over 1 hour on day 2 for the first course and on day 1 for all subsequent courses. Treatment repeats every 3 weeks for 4 courses. After completion of the last course, patients continue to receive trastuzumab once weekly until 1 year from date of initial trastuzumab dose.
    Intervention: Drug: doxorubicine, cyclophosphamide, trastuzumab, docetaxel
  • Experimental: 3
    Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, and 15. Patients also receive docetaxel IV over 1 hour and carboplatin IV over 30-60 minutes on day 2 for the first course and on day 1 for all subsequent courses. Treatment repeats every 3 weeks for a total of 6 courses. After completion of the last course, patients continue to receive trastuzumab once weekly until 1 year from date of initial trastuzumab dose.
    Intervention: Drug: trastuzumab, docetaxel, carboplatin
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
3150
November 2014
November 2014   (final data collection date for primary outcome measure)

Inclusion criteria:

  • Histologically proven breast cancer with an interval between definitive surgery that includes axillary lymph node involvement assessment and registration of less than or equal to 60 days. A central pathology review may be performed post randomization for confirmation of diagnosis and molecular studies. The same block used for her2neu determination prior to randomization may 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).
  • Patients must be either lymph node positive or high risk node negative. Lymph node positive patients will be defined as patients 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 patients will be defined as patients 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, ER and/or PR status is 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 LVEF (MUGA scan) and 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) ASAT (SGOT) and ALAT (SGPT) ≤ 2.5 UNL iii) Alkaline phosphatase ≤ 5 UNL iv) Patients 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 limit reached, the calculated creatinine clearance should be ≥ 60 mL/min.

  • Complete staging work-up within 3 months prior to registration. All patients will have bilateral mammography, chest X-ray (PA and lateral) and/or CT and/or MRI, abdominal ultrasound and/or CT scan and/or MRI, and bone scan. In cases of positive bone scans, bone X-ray evaluation is 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 will be performed within 4 weeks of registration. This is only for those centers who have 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 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 criteria.
  • Cardiac disease that would preclude the use of doxorubicin, docetaxel and Herceptin:

    1. any documented myocardial infarction
    2. angina pectoris that requires the use of antianginal medication
    3. any history of documented congestive heart failure
    4. Grade 3 or Grade 4 cardiac arrhythmia (NCI CTC, version 2.0)
    5. clinically significant valvular heart disease
    6. patients 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 is ≥ the lower limit of normal for the radiology facility;
    7. patients with poorly controlled hypertension i.e. diastolic greater than 100 mm/Hg. (Patients who are well controlled on medication are eligible for entry)
    8. patients who currently receive medications (digitalis, beta-blockers, calcium channel-blockers, etc) that alter cardiac conduction, if these medications are administered for cardiac arrhythmia, angina or congestive heart failure. If these medications are administered for other reasons (ie hypertension), the patient will be 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 patients treated at centers who have 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 ductal carcinoma in-situ (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. Patients must have 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 patient's potential participation in a clinical trial.

Female
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Belgium,   Bosnia and Herzegovina,   Brazil,   Bulgaria,   Canada,   Colombia,   Croatia,   Czech Republic,   Egypt,   Estonia,   France,   Germany,   Greece,   Hong Kong,   Hungary,   India,   Ireland,   Israel,   Italy,   Korea, Republic of,   Lebanon,   Mexico,   Poland,   Romania,   Russian Federation,   Slovakia,   Slovenia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Tunisia,   Turkey,   United Kingdom,   Uruguay,   Venezuela
 
NCT00021255
TAX_GMA_302, BCIRG 006
Not Provided
Sanofi
Sanofi
Cancer International Research Group
Study Director: AUSSEL Jean Philippe Sanofi
Sanofi
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP