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. (ADAPT; T-DM1)
Breast Cancer
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
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
Sites / Locations
- Breast Center of the University of Munich (LMU)
- Ev. Krankenhaus Bethesda Brustzentrum Niederrhien
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
T-DM1
T-DM1 + endocrine therapy
Trastuzumab + endocrine therapy
single agent T-DM1 for 12 weeks (3,6 mg/kg q3w)
Single agent T-DM1 for 12 weeks (3,6 mg/kg q3w) with standard endocrine therapy (tamoxifen in premenopausal women and an aromatase inhibitor in postmenopausal women, if no 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)with endocrine therapy tamoxifen in premenopausal women and an aromatase inhibitor in postmenopausal women, if not contraindications are present, in a standard daily dosage).