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
  Purpose

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.

Condition Intervention Phase
Breast Neoplasms
Drug: doxorubicine, cyclophosphamide, docetaxel
Drug: doxorubicine, cyclophosphamide, trastuzumab, docetaxel
Drug: trastuzumab, docetaxel, 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:
  • 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 ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: measured from the date of randomization up to the date of death of any cause. ] [ Designated as safety issue: No ]

Estimated Enrollment: 3150
Study Start Date: March 2002
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: doxorubicine, cyclophosphamide, docetaxel
doxorubicine IV, cyclophosphamide IV, docetaxel IV
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.
Drug: doxorubicine, cyclophosphamide, trastuzumab, docetaxel
doxorubicine IV, cyclophosphamide IV, trastuzumab IV, docetaxel IV
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.
Drug: trastuzumab, docetaxel, carboplatin
trastuzumab IV, docetaxel IV, carboplatin IV

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

  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

  Show 41 Study Locations
Sponsors and Collaborators
Sanofi
Cancer International Research Group
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
Last Updated: July 29, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 19, 2014