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 HE

• Status: Unknown status
• Trial end date: 2020-10-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: West German Study Group
• Collaborator: Roche Pharma AG
• Treatments: Ado-trastuzumab emtansine; Aromatase Inhibitors; Maytansine; Trastuzumab

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