Breast Cancer
Conditions
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.
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.
Interventions
DRUGT-DM1
DRUGTrastuzumab
Sponsors
Roche Pharma AG
West German Study Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Toxicity/cardiac safety | 5 years after treatment |
| Evaluation of dynamic test regarding prediction of 5-year event-free survival (EFS) | 5 year after treatment |
| Health-related quality of life (HRQL) | After 5 year after treatment of last patient |
| Overall safety in the three treatment arms | 5 years after treatment |
| Overall survival | 5 year after treamtment |
Countries
Germany
Outcome results
None listed