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. (ADAPT; T-DM1)

March 23, 2023 updated by: West German Study Group

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

380

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Munich, Germany
        • Breast Center of the University of Munich (LMU)
      • Mönchengladbach, Germany
        • Ev. Krankenhaus Bethesda Brustzentrum Niederrhien

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
Time Frame: after 3 weeks of treamtment
Response: pCR (residual cancer burden (RCB) 0-1) or resistance/low response (RCB II-III or progressive disease)
after 3 weeks of treamtment

Secondary Outcome Measures

Outcome Measure
Time Frame
Evaluation of dynamic test regarding prediction of 5-year event-free survival (EFS)
Time Frame: 5 year after treatment
5 year after treatment
Overall survival
Time Frame: 5 year after treamtment
5 year after treamtment
Toxicity/cardiac safety
Time Frame: 5 years after treatment
5 years after treatment
Overall safety in the three treatment arms
Time Frame: 5 years after treatment
5 years after treatment
Health-related quality of life (HRQL)
Time Frame: After 5 year after treatment of last patient
After 5 year after treatment of last patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West German Study Group

Collaborators

Roche Pharma AG

Investigators

  • Principal Investigator: Nadia Harbeck, Prof. Dr., Breast Center of the University of Munich (LMU), Universitätsfrauenklinik Großhadern, Munich, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2012

Primary Completion (Actual)

February 1, 2015

Study Completion (Anticipated)

October 1, 2024

Study Registration Dates

First Submitted

November 30, 2012

First Submitted That Met QC Criteria

December 7, 2012

First Posted (Estimate)

December 10, 2012

Study Record Updates

Last Update Posted (Actual)

March 24, 2023

Last Update Submitted That Met QC Criteria

March 23, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WSG-AM06/ADAPT HER2+/HR+

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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