ADAPT; T-DM1: 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.
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: T-DM1 single agent T-DM1 for 12 weeks (3,6 mg/kg q3w) |
Drug: T-DM1
|
| Experimental: T-DM1 + endocrine therapy 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). |
Drug: T-DM1
|
| Active Comparator: Trastuzumab + endocrine therapy 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). |
Drug: Trastuzumab
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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. [After 12 weeks]
pCR will be measured after 12 weeks of randomized treatment.
- 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. [after 3 weeks of treamtment]
Response: pCR (residual cancer burden (RCB) 0-1) or resistance/low response (RCB II-III or progressive disease)
Secondary Outcome Measures
- Evaluation of dynamic test regarding prediction of 5-year event-free survival (EFS) [5 year after treatment]
- Overall survival [5 year after treamtment]
- Toxicity/cardiac safety [5 years after treatment]
- Overall safety in the three treatment arms [5 years after treatment]
- Health-related quality of life (HRQL) [After 5 year after treatment of last patient]
Eligibility Criteria
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)
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All clinical N (cN)
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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)
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All clinical N (participation of patients with cN0, if cT1c is strongly recommended)
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Patients must qualify for neoadjuvant treatment
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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
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Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri
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Non-operable breast cancer including inflammatory breast cancer
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Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
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Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry
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Male breast cancer
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Concurrent pregnancy; patients of childbearing potential must implement
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a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment
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Breast feeding woman
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Sequential breast cancer
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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
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Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study
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Inadequate organ function (e.g. hepatic impairment, pulmonary disease, etc.)
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Uncompensated cardiac function (current unstable ventricular arrhythmia
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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)
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Severe dyspnea
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Pneumonitis
Abnormal blood values:
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Thrombocytopenia > CTCAE grade 1
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Increases in ALT/AST > CTCAE grade 1
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Hypokalaemia > CTCAE grade 1
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Neutropenia > CTCAE grade 1
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Anaemia > CTCAE grade 1
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Breast Center of the University of Munich (LMU) | Munich | Germany | ||
| 2 | Ev. Krankenhaus Bethesda Brustzentrum Niederrhien | Mönchengladbach | Germany |
Sponsors and Collaborators
- West German Study Group
- Roche Pharma AG
Investigators
- Principal Investigator: Nadia Harbeck, Prof. Dr., Breast Center of the University of Munich (LMU), Universitätsfrauenklinik Großhadern, Munich, Germany
- Study Chair: Ulrike Nitz, Prof. Dr., Ev. Krankenhaus Bethesda Brustzentrum Niederrhein, Mönchengladbach, Germany
Study Documents (Full-Text)
None provided.More Information
Publications
- WSG-AM06/ADAPT HER2+/HR+