Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments t-dm1, trastuzumab
Phase phase 2
Target HER2
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+

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
single agent T-DM1 for 12 weeks (3,6 mg/kg q3w)
t-dm1
(Experimental)
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).
t-dm1
(Active Comparator)
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).
trastuzumab Herceptin

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
Evaluation of dynamic test regarding prediction of 5-year event-free survival (EFS)
time frame: 5 year after treatment
Overall survival
time frame: 5 year after treamtment
Toxicity/cardiac safety
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

Eligibility Criteria

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

Additional Information

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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2015.
Information provided to ClinicalTrials.gov by West German Study Group.