Trial of Neoadjuvant EndoTAG-1 in Combination With Paclitaxel in HER2-negative Breast Cancer

The study hypothesis is that the new drug EndoTAG-1 will improve tumor volume reduction as measured by Magnetic Resonance Imaging when added to a standard chemotherapy regimen of weekly paclitaxel. This is a prospective single-center study that will investigate the activity of EndoTAG-1 + paclitaxel combination therapy in patients with HER2-negative breast cancer that are candidate for receiving chemotherapy before surgery (neoadjuvant chemotherapy).

This is a prospective, single-center, open-label phase II clinical trial investigating the activity of EndoTAG-1 + paclitaxel combination therapy in patients with HER2-negative BC candidate for neoadjuvant chemotherapy, as measured by the decrease in MRI-estimated tumour volume at the end of EndoTAG-1 + paclitaxel administration. Patients will be stratified by hormone receptor status.

A total of 20 female patients with non-metastatic HER2-negative breast cancer candidate for neoadjuvant chemotherapy and meeting all study eligibility criteria will receive 12 weekly infusions of EndoTAG-1 (22 mg/m2 liposomal paclitaxel) in combination with paclitaxel (70 mg/m2) followed by 3 cycles of FEC (Fluorouracil 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2) every 3 weeks (experimental group) The study hypothesis is that EndoTAG-1 will improve MRI- estimated volume reduction when added to weekly paclitaxel. The null hypothesis is that combination has no or a negligible effect on volume reduction (defined as lower or equal to a 50% decrease) versus the alternative hypothesis that the combination yields at least a 80% average decrease in MRI- estimated volume at the end of weekly paclitaxel and EndoTAG-1 administration from baseline

Eligibility Criteria:
Inclusion Criteria:

1. newly diagnosed histologically confirmed BC with breast infiltrating carcinoma of histological grade \> 1 (either operable, or locally advanced or inflammatory) candidate for neoadjuvant chemotherapy
2. HER2-negative tumor, defined according to immunohistochemistry or using fluorescent in-situ hybridization (FISH)
3. ECOG performance status 0 or 1
4. Gender: female
5. Age : \>= 18 years old
6. Negative pregnancy test (females of childbearing potential)
7. Willingness to perform double-barrier-contraception during study and for 6 months post chemotherapy treatment (females of childbearing potential)
8. Signed informed consent

Exclusion Criteria:

1. Metastatic or relapsed disease
2. Major surgery \< 3 weeks prior to enrollment
3. Severe pulmonary obstructive or restrictive disease
4. Uncontrolled inflammatory disease (autoimmune or infectious)
5. Clinically significant cardiac disease (NYHA stadium \> 2)
6. Results of laboratory tests (hematology, chemistry) outside specified limits:

   * WBC ≤ 3 x 109/L
   * ANC \< 1.5 x 109/L
   * Platelets \< 100 x 109/L
   * Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l)
   * PTT/ INR \> 1.5 x ULN
   * AST or ALT \> 2.5 x ULN
   * Alkaline Phosphatase \> 2 x ULN
   * Total Bilirubin \> 1.5 x ULN
7. Pregnancy or nursing status
8. Known positive HIV testing
9. Known hypersensitivity to any component of the EndoTAG-1, paclitaxel or FEC formulations
10. History of malignancy other than breast cancer \< 5 years prior to enrollment, except skin cancer (i.e. basal or squamous cell carcinoma) treated locally
11. History of active or significant neurological disorder or psychiatric disorder that would prohibit the understanding and giving of informed consent, or would interfere in the clinical and radiological evaluation of central nervous system during the trial
12. Concurrent treatment with other experimental products. Participation in another clinical trial with any investigational product within 30 days prior to study entry