A Prospective, Randomized, Multicenter, Open-label Comparison of Pre-surgical Combination of Trastuzumab and Pertuzumab With Concurrent Taxane Chemotherapy or Endocrine Therapy Given for Twelve Weeks With a Quality of Life Assessment of Trastuzumab, Pertuzumab in Combination With Standard (Neo)Adjuvant Treatment in Patients With Operable HER2+/HR+ Breast Cancer.

PH002-TP-II

This is a prospective, phase IIa, multicenter, randomized, open-label study comparing a pre-surgical combination of trastuzumab and pertuzumab with concurrent weekly paclitaxel chemotherapy or endocrine therapy given for 12 weeks with a quality of life assessment for 40 additional weeks in patients with operable HER2+/HR+ breast cancer.

2017-10-05

2020-07-14

2024-03-04

Completed

Early phase I

257

Inclusion Criteria: * Female patients, age at diagnosis 18 years and older * Histologically confirmed unilateral primary invasive carcinoma of the breast * Patients must qualify for neoadjuvant treatment as follows: * No clinical evidence for distant metastasis (M0) * Clinical cT1c-T4a-c (participation of patients with tumors \> cT2 is strongly recommended) and no evidence for distant metastases (M0) * All clinical N (participation of patients with cN+, also in case of cT1c, is strongly recommended) * Known positive HR-status and centrally confirmed HER2+-status by IHC/FISH * Patients need to fulfill adequate blood count and organ function to receive chemotherapy (see exclusion criteria). * 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 registration in premenopausal patients * Patients of childbearing potential must accept to implement a highly effective (less than 1% failure rate according to Pearl index) non-hormonal contraceptive measures during the study treatment and for 6 months following the last dose of study treatment (trastuzumab and pertuzumab) such as: * Intrauterine device (IUD) * bilateral tubal occlusion * vasectomised partner * sexual abstinence * 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 * LVEF \> 55%; LVEF within normal limits of each institution measured by echocardiography (within 42 days prior to randomization) * Normal ECG (within 42 days prior to randomization) 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 * Concurrent treatment with other experimental drugs and participation in another clinical trial or clinical research project within 30 days prior to study entry is excluded * Male breast cancer * Concurrent pregnancy * Breastfeeding * Sequential breast cancer * Reasons indicating risk of poor compliance * Known polyneuropathy ≥ grade 2 * Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including but not confined to: * Uncompensated chronic heart failure or systolic dysfunction (LVEF \< 55%, CHF NYHA classes II-IV), * unstable arrhythmias requiring treatment i.e., atrial tachycardia with a heart rate ≥ 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block, * Angina pectoris within the last 6 months requiring anti-anginal medication, * Clinically significant valvular heart disease, * Evidence of myocardial infarction on electrocardiogram (ECG), * Poorly controlled hypertension (e.g., systolic \> 180 mm Hg or diastolic \> 100 mm Hg). * Inadequate organ function including but not confined to: * hepatic impairment (Child Pugh Class C) * pulmonary disease (severe dyspnea at rest requiring oxygen therapy) * 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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 257, 'type': 'ACTUAL'}}

2024-04-17