ADAPT - Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer

Inclusion Criteria:

• Female patients, age at diagnosis 18 - 75 years
• 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 patients receiving chemotherapy:

• Laboratory requirements for patients receiving neoadjuvant chemotherapy (within 14 days prior to induction treatment):

  • Leucocytes >= 3.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Hemoglobin >= 10 g/dL
  • Total bilirubin <= 1 x ULN
  • ASAT (SGOT) and ALAT (SGPT) <= 2.5 x UNL
  • Creatinine <= 175 µmol/L (2 mg/dl)
• 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 or 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 interventional clinical trial with or without 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
• Patients not able to consent

Additional Exclusion Criteria for patients receiving chemotherapy:

• 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 acute cystitis and ischuria and chronic kidney disease
• Uncompensated cardiac function

• Inadequate organ function including:

  • Leucocytes < 3.5 x 10^9/l
  • Platelets < 100 x 10^9/l
  • Bilirubin above normal limits
  • Alkaline phosphatase >= 5 x UNL
  • ASAT and/or ALAT associated with AP > 2.5 x UNL