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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by West German Study Group
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
West German Study Group
ClinicalTrials.gov Identifier:
NCT01745965
First received: November 30, 2012
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: T-DM1
Drug: Trastuzumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by West German Study Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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. [ Time Frame: after 3 weeks of treamtment ] [ Designated as safety issue: No ]
    Response: pCR (residual cancer burden (RCB) 0-1) or resistance/low response (RCB II-III or progressive disease)


Secondary Outcome Measures:
  • Evaluation of dynamic test regarding prediction of 5-year event-free survival (EFS) [ Time Frame: 5 year after treatment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 5 year after treamtment ] [ Designated as safety issue: No ]
  • Toxicity/cardiac safety [ Time Frame: 5 years after treatment ] [ Designated as safety issue: Yes ]
  • Overall safety in the three treatment arms [ Time Frame: 5 years after treatment ] [ Designated as safety issue: Yes ]
  • Health-related quality of life (HRQL) [ Time Frame: After 5 year after treatment of last patient ] [ Designated as safety issue: No ]

Estimated Enrollment: 380
Study Start Date: November 2012
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Herceptin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01745965

Contacts
Contact: Daniel Hofmann, M.Sc. +49216156623 ext 17 daniel.hofmann@wsg-online.com
Contact: Sebastian Räth, PhD +49308868688 ext 13 sebastian.raeth@wsg-online.com

Locations
Germany
Breast Center of the University of Munich (LMU) Recruiting
Munich, Germany
Contact: Nadia Harbeck, Prof. Dr.    +49897095 ext 4531    nadia.harbeck@med-uni-muenchen.de   
Sub-Investigator: Rachel Würstlein, Dr. med.         
Ev. Krankenhaus Bethesda Brustzentrum Niederrhien Recruiting
Mönchengladbach, Germany
Contact: Ulrike Nitz, Prof. Dr.    +492161981 ext 2330    ulrike.nitz@wsg-online.com   
Principal Investigator: Raquel von Schumann, Dr. med.         
Sponsors and Collaborators
West German Study Group
Roche Pharma AG
Investigators
Principal Investigator: Nadia Harbeck, Prof. Dr. Breast Center of the University of Munich (LMU), Universitätsfrauenklinik Großhadern, Munich, Germany
Study Chair: Ulrike Nitz, Prof. Dr. Ev. Krankenhaus Bethesda Brustzentrum Niederrhein, Mönchengladbach, Germany
  More Information

Publications:
Responsible Party: West German Study Group
ClinicalTrials.gov Identifier: NCT01745965     History of Changes
Other Study ID Numbers: WSG-AM06/ADAPT HER2+/HR+
Study First Received: November 30, 2012
Last Updated: July 31, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Trastuzumab
Ado-trastuzumab emtansine
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Maytansine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on August 18, 2014