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

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.

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.

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