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.

Breast Cancer Clinical Trial

— ADAPT; T-DM1  

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01745965
• Other study ID #: WSG-AM06/ADAPT HER2+/HR+
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 2012
• Est. completion date: October 2024

Study information

• Verified date: March 2023
• Source: West German Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 380
• Est. completion date: October 2024
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• T-DM1

• Trastuzumab

Locations

Country	Name	City	State
Germany	Ev. Krankenhaus Bethesda Brustzentrum Niederrhien	Mönchengladbach
Germany	Breast Center of the University of Munich (LMU)	Munich

Sponsors (2)

Lead Sponsor	Collaborator
West German Study Group	Roche Pharma AG

Country where clinical trial is conducted

Germany, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Evaluation of dynamic test regarding prediction of 5-year event-free survival (EFS)		5 year after treatment
Secondary	Overall survival		5 year after treamtment
Secondary	Toxicity/cardiac safety		5 years after treatment
Secondary	Overall safety in the three treatment arms		5 years after treatment
Secondary	Health-related quality of life (HRQL)		After 5 year after treatment of last patient