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.

NCT01745965 | Completed Phase 2 DMC

• 1 other identifier: WSG-AM06/ADAPT HER2+/HR+
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 2

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  pCR will be measured after 12 weeks of randomized treatment.

  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.

  Response: pCR (residual cancer burden (RCB) 0-1) or resistance/low response (RCB II-III or progressive disease)

  after 3 weeks of treamtment

Secondary Outcomes (5)

• 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

Study Arms (3)

T-DM1

EXPERIMENTAL

single agent T-DM1 for 12 weeks (3,6 mg/kg q3w)

Drug: T-DM1

T-DM1 + endocrine therapy

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).

Drug: T-DM1

Trastuzumab + endocrine therapy

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).

Drug: Trastuzumab

Interventions

T-DM1 DRUG

T-DM1; T-DM1 + endocrine therapy

Trastuzumab DRUG

Also known as: Herceptin

Trastuzumab + endocrine therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• West German Study Group: lead
• Roche Pharma AG: collaborator

Study Sites (2)

Ev. Krankenhaus Bethesda Brustzentrum Niederrhien

Mönchengladbach, Germany

Location

Breast Center of the University of Munich (LMU)

Munich, Germany

Location

Related Publications (1)

• Hofmann D, Nitz U, Gluz O, Kates RE, Schinkoethe T, Staib P, Harbeck N. WSG ADAPT - adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early breast cancer: study protocol for a prospective, multi-center, controlled, non-blinded, randomized, investigator initiated phase II/III trial. Trials. 2013 Aug 19;14:261. doi: 10.1186/1745-6215-14-261.

  PMID: 23958221 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nadia Harbeck, Prof. Dr.

  Breast Center of the University of Munich (LMU), Universitätsfrauenklinik Großhadern, Munich, Germany

  PRINCIPAL INVESTIGATOR

• Ulrike Nitz, Prof. Dr.

  Ev. Krankenhaus Bethesda Brustzentrum Niederrhein, Mönchengladbach, Germany

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2012
• First Posted: December 10, 2012
• Study Start: November 1, 2012
• Primary Completion: February 1, 2015
• Study Completion: January 15, 2025
• Last Updated: February 27, 2025

Record last verified: 2025-02

Locations

DE (2)