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.

NCT ID: NCT01745965

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 380 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2025-01-15

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

T-DM1

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

Group Type: EXPERIMENTAL

T-DM1

Intervention Type: DRUG

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).

Group Type: EXPERIMENTAL

T-DM1

Intervention Type: DRUG

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).

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: DRUG

Interventions

T-DM1

Intervention Type: DRUG

Trastuzumab

Intervention Type: DRUG

Other Intervention Names

Herceptin

Eligibility 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

West German Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nadia Harbeck, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

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

Ulrike Nitz, Prof. Dr.

Role: STUDY_CHAIR

Ev. Krankenhaus Bethesda Brustzentrum Niederrhein, Mönchengladbach, Germany

Locations

Ev. Krankenhaus Bethesda Brustzentrum Niederrhien

Mönchengladbach, , Germany

Breast Center of the University of Munich (LMU)

Munich, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 23958221 (View on PubMed)

Other Identifiers

WSG-AM06/ADAPT HER2+/HR+

Identifier Type: -

Identifier Source: org_study_id