A Prospective, Randomized Multicenter, Open-label Comparison of Preoperative Trastuzumab Emtansine (T-DM1) With or Without Standard Endocrine Therapy vs. Trastuzumab With Standard Endocrine Therapy Given for Twelve Weeks in Patients With Operable HER2+/HR+ Breast Cancer Within the ADAPT Protocol.
This trial is active, not recruiting.
|Sponsor||West German Study Group|
|Collaborator||Roche Pharma AG|
|Start date||November 2012|
|End date||February 2015|
|Trial size||380 participants|
|Trial identifier||NCT01745965, WSG-AM06/ADAPT HER2+/HR+|
Trial to optimize neoadjuvant therapy for HER overexpression and co-expressing of hormone receptors(ER and/or PR) breast cancer (HEr2+/HR+).
A new high potential trastuzumab conjugate T-DM1(trastuzumab was linked with the cytotoxic agent mertansine DM1)was tested with endocrine therapy and without against a standard arm with trastuzumab and endocrine therapy.
|United States||No locations recruiting|
|Other Countries||No locations recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||parallel assignment|
Comparison of the pCR rates in patients with HER2+/HR+ breast cancer treated by preoperative T-DM1 with or without standard endocrine therapy or trastuzumab with endocrine therapy.
time frame: After 12 weeks
Evaluation of dynamic testing (based on proliferation/apoptosis changes in serial biopsy and imaging by MRI) after three weeks of treatment as a surrogate parameter for response.
time frame: after 3 weeks of treamtment
Evaluation of dynamic test regarding prediction of 5-year event-free survival (EFS)
time frame: 5 year after treatment
time frame: 5 year after treamtment
time frame: 5 years after treatment
Overall safety in the three treatment arms
time frame: 5 years after treatment
Health-related quality of life (HRQL)
time frame: After 5 year after treatment of last patient
Female participants at least 18 years old.
Inclusion Criteria: - Female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for ADAPT Elderly) - Histologically confirmed unilateral primary invasive carcinoma of the breast - Clinical T1 - T4 (except inflammatory breast cancer) - All clinical N (cN) - No clinical evidence for distant metastasis (M0) - Known HR status and HER2 status (local pathology) Tumor block available for central pathology review - Performance Status ECOG ≤ 1 or KI ≥ 80% - Negative pregnancy test (urine or serum) within 7 days prior to start of induction treatment in premenopausal patients - 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 the local regulatory requirements - The patient must be accessible for treatment and follow-up Additional Inclusion criteria for participation in the HER2+/HR+ sub-protocol: - Confirmed ER and/or PR positive and HER2+ by central pathology - Clinical cT1c - T4a-c (participation of patients with tumors >cT2 is strongly recommended) - All clinical N (participation of patients with cN0, if cT1c is strongly recommended) - Patients must qualify for neoadjuvant treatment - LVEF > 50%; LVEF within normal limits of each institution measured by echocardiography and normal ECG (within 42 days prior to induction treatment) Exclusion Criteria: - Known hypersensitivity reaction to the compounds or incorporated substances - Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri - Non-operable breast cancer including inflammatory breast cancer - Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor - Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry - Male breast cancer - Concurrent pregnancy; patients of childbearing potential must implement - a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment - Breast feeding woman - Sequential breast cancer - Reasons indicating risk of poor compliance Patient not able to consent Additional Exclusion Criteria for participation in the HER2+/HR+ sub-protocol: - Known polyneuropathy ≥ grade 2 - Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study - Inadequate organ function (e.g. hepatic impairment, pulmonary disease, etc.) - Uncompensated cardiac function (current unstable ventricular arrhythmia - requiring treatment, history of symptomatic CHF NYHA classes II-IV), history of myocardial infarction or unstable angina pectoris within 6 months of enrollment, history of severe hypertension, CAD - coronary artery disease) - Severe dyspnea - Pneumonitis Abnormal blood values: - Thrombocytopenia > CTCAE grade 1 - Increases in ALT/AST > CTCAE grade 1 - Hypokalaemia > CTCAE grade 1 - Neutropenia > CTCAE grade 1 - Anaemia > CTCAE grade 1
|Official title||A Prospective, Randomized Multicenter, Open-label Comparison of Preoperative Trastuzumab Emtansine (T-DM1) With or Without Standard Endocrine Therapy vs. Trastuzumab With Standard Endocrine Therapy Given for Twelve Weeks in Patients With Operable HER2+/HR+ Breast Cancer Within the ADAPT Protocol.|
|Principal investigator||Nadia Harbeck, Prof. Dr.|
|Description||the neoadjuvant therapy Patients with HER2+/HR+ (HER2+ and ER+ and/or PR+) tumor will receive single agent T-DM1 for 12 weeks (3,6 mg/kg q3w) with or without standard endocrine therapy (tamoxifen in premenopausal women and an aromatase inhibitor in postmenopausal women, if not contraindications are present, in a standard daily dosage). The control group will receive trastuzumab in 3-weekly schedule (8 mg/kg as loading dose and then 6 mg/kg q3w) in combination with the same standard endocrine therapy, if no contraindications are existent.|
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