A Prospective, Multicenter, Open-label 12 Week Neoadjuvant Phase II Trial Optimizing Taxane Therapy in Elderly Patients With Low Response

A Prospective, Multicenter, Open-label Comparison of Pre-surgical Myocet/ Cyclophosphamide (MC) q3w Followed by Either MC or Paclitaxel - Depending on Early Response Assessment by Ultrasound or by Toxicity for Elderly Non Frail Primary Breast Cancer Patients With Increased Risk of Relapse.

Comparison of pre-surgical Myocet/ Cyclophosphamide (MC) q3w followed by either MC or Paclitaxel - depending on early response assessment by ultrasound or by toxicity for elderly non frail primary breast cancer patients with increased risk of relapse.

General Inclusion Criteria for ADAPT:

• Female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for ADAPT Elderly)

• Candidate for chemotherapy on the basis of conventional criteria

• Histologically confirmed unilateral primary invasive carcinoma of the breast

• Clinical T1 - T4a-c

• 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%

• 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

• 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 chemotherapy)

  • Laboratory requirements :

    • Leucocytes ≥ 3.5 x 109/L
    • Platelets ≥ 100 x 109/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)

Additional inclusion criteria ADAPT Elderly:

• ≥ 70 years old
• Charlson scale ≤ 2
• HR+/HER2- disease: if RS and sequential testing are available N0-1/RS 12-25/poor response or N0-1/RS ≥26
• All G3 with Ki-67 ≥40% in tumors >1cm
• All N2
• All TN
• All subtypes

General Exclusion Criteria for ADAPT:

• 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 (concurrent participation in non-interventional post authorization safety studies not influencing the primary study endpoints is allowed, e.g. WSG PROTROCA for evaluation of primary/secondary G-CSF prophylaxis)
• Male breast cancer
• Sequential breast cancer
• Reasons indicating risk of poor compliance
• Patient not able to consent

Additional Exclusion Criteria ADAPT Elderly:

• 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 12 months of enrollment, history of severe hypertension, CAD - coronary artery disease)
• Severe dyspnea
• Pneumonitis
• 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