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Trial record 1 of 1 for:    NCT01745965
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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)

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ClinicalTrials.gov Identifier: NCT01745965
Recruitment Status : Active, not recruiting
First Posted : December 10, 2012
Last Update Posted : July 23, 2019
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
West German Study Group

Tracking Information
First Submitted Date  ICMJE November 30, 2012
First Posted Date  ICMJE December 10, 2012
Last Update Posted Date July 23, 2019
Actual Study Start Date  ICMJE November 2012
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2012)
  • 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.
  • 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2012)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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.
Official Title  ICMJE 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.
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: T-DM1
  • Drug: Trastuzumab
    Other Name: Herceptin
Study Arms  ICMJE
  • Experimental: T-DM1
    single agent T-DM1 for 12 weeks (3,6 mg/kg q3w)
    Intervention: 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).
    Intervention: 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).
    Intervention: Drug: Trastuzumab
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 7, 2012)
380
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2020
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01745965
Other Study ID Numbers  ICMJE WSG-AM06/ADAPT HER2+/HR+
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party West German Study Group
Study Sponsor  ICMJE West German Study Group
Collaborators  ICMJE Roche Pharma AG
Investigators  ICMJE
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
PRS Account West German Study Group
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP