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

• Conditions: ode positive and high risk node negative patients with operable breast cancer containing the HER2 alteration; MedDRA version: 17.1Level: PTClassification code 10057654Term: Breast cancer femaleSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2008-005127-29-SK
• Lead Sponsor: Sanofi-aventis groupe

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-10-14
• Last Update Posted: 16 March 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 3263

Inclusion Criteria

1.Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to local regulatory requirements.
2. 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. If the definite surgery and the axillary node dissection are performed in two different days, both days should be within the 60 days window. A central pathology review may be performed post randomization for confirmation of diagnosis and molecular studies. The same block used for HER2 determination prior to randomization may be used for the central pathology review. See Appendix 3* for details on this process.
3. 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 . Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and/or ductal carcinoma in situ (DCIS). The finding of lobular carcinoma in-situ will not be scored as a positive margin.
4. 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 (pN0) among a minimum of 6 resected lymph nodes or negative sentinel node biopsy (pN0) AND at least one of the following factors: tumor size > 2 cm, ER and PR status is negative, histologic and/or nuclear grade 2-3, or age < 35 years.
Tumor must show the presence of the HER2 gene amplification by Fluorescence In-Situ Hybridization (FISH analysis) by a designated central laboratory (see Appendix 3 for complete details).
6. 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 PR 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 ER assayed in order to determine
hormonal receptor status.)
7. Age = 18 years and age = 70 years. The upper age limit is not meant to be exclusionary but rather is based on the lack of safety data for the TCH regimen in women >70 years of age.
8. Karnofsky Performance status index = 80%.
9. Normal cardiac function must be confirmed by LVEF (echocardiography or MUGA scan) and ECG within 3 months prior to registration. The result of the echocardiography or MUGA must be equal to or above the lower limit of normal for the
institution.
10. 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

Exclusion Criteria

1. Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
2. Prior anthracycline therapy, taxoids (paclitaxel, docetaxel) or platinum salts for any malignancy.
3. Prior radiation therapy for breast cancer.
4. Bilateral invasive breast cancer.
5. Pregnant, or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive
measures during study treatment (chemotherapy, Herceptin® and tamoxifen therapy) and must have negative urine or
serum pregnancy test within 7 days prior to registration.
6. Any T4 or N2 or known N3 or M1 breast cancer.
7. Pre-existing motor or sensory neurotoxicity of a severity = grade 2 by NCI criteria.
8. Cardiac disease that would preclude the use of doxorubicin, docetaxel and Herceptin®.
a) any documented myocardial infarction
b) angina pectoris that requires the use of antianginal medication
c) any history of documented congestive heart failure
d) Grade 3 or Grade 4 cardiac arrhythmia (NCI CTC, version 2.0)
e) clinically significant valvular heart disease
f) patients with cardiomegaly on chest x-ray or ventricular hypertrophy on ECG, unless they demonstrate by
echocardiography or MUGA scan within the past 3 months that the LVEF is = the lower limit of normal for the
radiology facility;
g) patients with poorly controlled hypertension i.e. diastolic greater than 100 mm/Hg. (Patients who are well
controlled on medication are eligible for entry
h) 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.
9. Other serious illness or medical condition:
a) history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would
prohibit the understanding and giving of informed consent
b) active uncontrolled infection
c) active peptic ulcer, unstable diabetes mellitus
d) patients with symptomatic, intrinsic lung disease resulting in dyspnea
10. Past or current history of neoplasm other than breast carcinoma, except for:
a) curatively treated non-melanoma skin cancer
b) in situ carcinoma of the cervix
c) other cancer curatively treated and with no evidence of disease for at least 10 years
d) ipsilateral ductal carcinoma in-situ (DCIS) of the breast
e) lobular carcinoma in-situ (LCIS) of the breast
f) DCIS involving the contralateral breast removed by mastectomy
11. Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators
(SERMs), either for osteoporosis or prevention of breast cancer. Patients must have discontinued these agents prior to
randomization.
12. Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose (= 20 mg
methylprednisolone or equivalent).
13. Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must be stopped prior to
randomization.
14. Definite contraindications for the use of corticosteroids.
15. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not
marketed drug within 30 days prior to study entry.
16. Concurrent treatment with any other anti-cancer the

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified