A Prospective, Randomized Multicenter, Open-label Comparison of Preoperative Combination of Trastuzumab and Pertuzumab With or Without Concurrent Taxane Chemotherapy Given for Twelve Weeks in Patients With Operable HER2+/HR- Breast Cancer Within the ADAPT Protocol

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Paclitaxel

• Registration Number: NCT01817452
• Lead Sponsor: West German Study Group

Brief Summary

Trial to evaluate efficacy of dual blockade with two anti-HER2 agents with or without chemotherapy backbone within the ADAPT trial.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-03-18
• Study First Submitted QC: 2013-03-22
• Study First Posted: 2013-03-25
• Study Start: 2014-03
• Primary Completion: 2025-01-15
• Study Completion: 2025-01-15
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-25
• Last Update Posted: 2025-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 220

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 HR-/HER2+ sub-protocol:

• Confirmed ER and PR negative 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 at least 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
• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	Trastuzumab	Trastuzumab + Pertuzumab + Paclitaxel
Arm A	Trastuzumab	Trastuzumab + Pertuzumab
Arm A	Pertuzumab	Trastuzumab + Pertuzumab
Arm B	Pertuzumab	Trastuzumab + Pertuzumab + Paclitaxel
Arm B	Paclitaxel	Trastuzumab + Pertuzumab + Paclitaxel

Primary Outcome Measures

Name	Time	Method
Definition of a biomarker (profile) characterizing "good responders" to dual blockade T and P anti-HER2 blockade that have similar pCR rates as patients treated with identical dual anti-HER2 blockade + taxane backbone	After 12 weeks of therapy	pCR will be measured after 12 weeks of randomized treatment.

Trial Locations

Locations (1)

Ev. Krankenhaus Bethesda Brustzentrum Niederrhien; 🇩🇪 Moenchengladbach, Germany