Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)

Inclusion Criteria: Patients will be eligible for study participation only if they comply with the followingcriteria:

• Written informed consent for all study according to local regulatory requirementsprior to beginning specific protocol procedures.

• Complete baseline documentation must be sent to GBG Forschungs GmbH.

• Unilateral or bilateral primary carcinoma of the breast, confirmed histologically bycore biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is notallowed. In case of bilateral cancer, the investigator has to decide prospectivelywhich side will be evaluated for the primary endpoint.

• Tumor lesion in the breast with a palpable size of >= 2 cm or a sonographical size of >= 1 cm in maximum diameter. The lesion has to be measurable in two dimensions,preferably by sonography. In case of inflammatory disease, the extent of inflammationcan be used as measurable lesion.

• Patients must be in the following stages of disease:

• • cT2 - cT4a-d or

• cT1c and cN+ or

• • cT1c and pNSLN+ or
• • cT1c and ER-neg and PR-neg or
• • cT1c and Ki67 > 20%
• • cT1c and HER2-pos

• In patients with multifocal or multicentric breast cancer, the largest lesionshould be measured.

• Centrally confirmed ER/PR/HER-2, Ki-67 and SPARC status detected on core biopsy. ER/PRpositive is defined as >1% stained cells and HER2-positive is defined as IHC 3+ orin-situ hybridisation (ISH) ratio >2.0. Formalin-fixed, paraffin-embedded (FFPE)breast tissue from core biopsy has therefore to be sent to the Dept. of Pathology atthe Charité, Berlin prior to randomization.

• Age >= 18 years.

• Karnofsky Performance status index >= 80%.

• Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF orshortening fraction) within 3 months prior to randomization. Results must be above thenormal limit of the institution. For patients with HER2-positive tumors LVEF must be >= 55%.

• Laboratory requirements:

• Hematology

• • Absolute neutrophil count (ANC) >= 2.0 x 109 / L and

• Platelets >= 100 x 109 / L and

• Hemoglobin >= 10 g/dL (>= 6.2 mmol/L)

• Hepatic function

• • Total bilirubin < 1.5x UNL and

• ASAT (SGOT) and ALAT (SGPT) <= 1.5x UNL and

• Alkaline phosphatase <= 2.5x UNL.

• Negative pregnancy test (urine or serum) within 14 days prior to randomization for allwomen of childbearing potential.

• Complete staging work-up within 3 months prior to randomization. All patients musthave bilateral mammography, breast ultrasound (<= 21 days), breast MRI (optional),chest X-ray (PA and lateral), abdominal ultrasound or CT scan or MRI, and bone scandone. In case of positive bone scan, bone X-ray is mandatory. Other tests may beperformed as clinically indicated.

• Patients must be available and compliant for central diagnostics, treatment andfollow-up.

Exclusion Criteria:

• Prior chemotherapy for any malignancy.

• Prior radiation therapy for breast cancer.

• Pregnant or lactating patients. Patients of childbearing potential must implementadequate non-hormonal contraceptive measures (barrier methods, intrauterinecontraceptive devices, sterilization) during study treatment.

• Inadequate general condition (not fit for anthracycline-taxane-targeted agents-basedchemotherapy).

• Previous malignant disease without being disease-free for less than 5 years (exceptCIS of the cervix and non-melanomatous skin cancer).

• Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease,angina pectoris requiring antianginal medication, previous history of myocardialinfarction, evidence of transmural infarction on ECG, uncontrolled or poorlycontrolled arterial hypertension (i.e. BP >160 / 90 mm Hg under treatment with twoantihypertensive drugs), rhythm abnormalities requiring permanent treatment,clinically significant valvular heart disease.

• History of significant neurological or psychiatric disorders including psychoticdisorders, dementia or seizures that would prohibit the understanding and giving ofinformed consent.

• Persons who have been admitted to an institution by order of jurisdictional orgovernmental grounds.

• Pre-existing motor or sensory neuropathy of grade 2 or more by NCI-CTC criteria v 4.0.

• Currently active infection.

• Definite contraindications for the use of corticosteroids.

• Known hypersensitivity reaction to one of the compounds or incorporated substancesused in this protocol.

• Concurrent treatment with:

• • chronic corticosteroids unless initiated > 6 months prior to study entry and at lowdose (10 mg or less methylprednisolone or equivalent).
• • sex hormones. Prior treatment must be stopped before study entry.
• • other experimental drugs or any other anti-cancer therapy.

• Participation in another clinical trial with any investigational, not marketed drugwithin 30 days prior to study entry.

• Male patients.