study to compare neoadjuvant combination of trastuzumab and pertuzumab with concurrent taxane chemotherapy or endocrine therapy and quality of life assessment under adjuvant therapy in operable her2+/hr+ breast cancer patients

Conditions: Breast Neoplasms

Summary: 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.


Eligibility criteria:
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

Keywords: hormone receptor positive human epidermal growth factor receptor 2 positive early breast cancer hr+/her2+