Multicenter Clinical Trial in subjects with HER2-negative primary tumors. The subjects will be evaluated for the presence of HER2 positive Circulating Tumor Cells (CTCs) in blood. In case of at least one HER2-positive CTC in blood, the subject will be randomized to receive either (nabTM)-paclitaxel + trastuzumab (ARM A) or (nabTM)-paclitaxel (ARM B).

Phase 1

Conditions: Metastatic Breast Cancer in HER2- positive CTC with primary HER2-negative.
MedDRA version: 16.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-005352-41-IT

Lead Sponsor: AZIENDA OSPEDALIERA ISTITUTI OSPITALIERI DI CREMONA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 86

Inclusion Criteria

1.Signed written informed consent.
2.Age =18 years.
3.ECOG 0-2
4.At least one clinically or radiologically measurable lesion and/or non-measurable disease evaluable according to Response Evaluation Criteria In Solid Tumors (RECIST version 1.1). Osteoblastic/osteolytic bone metastasis will be included.
5.HER2 negative on primary tumor (HER-2 score of 0 or 1+/2+ with FISH not amplified) as locally diagnosed.
6.Detection of at least 1 HER2+ve CTC.
7.Patients may have received chemotherapy/hormonotherapy as neo/adjuvant treatment.
8.Adequate bone marrow, renal and hepatic functions: ANC greater than 1.5x10^9/l, platelets greater than 100x10^9/l, serum creatinine < 1.5 x UNL, serum AST/ALT < 1.5 x UNL unless liver metastasis < 2.5 x UNL.
9.Adequate cardiac function: left ventricular ejection fraction (LVEF) at rest measured by echocardiography or MUGA scan must be no lower than the local normal limit.
10.Troponin level below the cut-off.
11.Absence of clinically significant cardiovascular disease (e.g. myocardial infarction, unstable angina), New York Hearth Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease within 12 months prior to day 1 on study.
12.Geographically accessible for follow-up.
13.Pregnancy test negative.
14.For women of childbearing potential who are sexually active, agreement to use a highly effective, non-hormonal form of contraception or two effective forms of non-hormonal contraception during and for at least 6 months post-study treatment.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

1.Previous chemotherapy or hormonotherapy for metastatic disease
2.Any psychiatric disorder that would impair the understanding and giving of informed consent.
3.Male patients
4.Non evaluable lesions as ascitic, pleural and pericardial effusions, carcinomatous lymphangitis of the lung, meningeal involvement.
5.Pregnant or lactating patients.
6.History of atrial ventricular arrhythmia, congestive heart failure or angina pectoris, even if medically controlled; uncontrolled hypertension; history of 2nd or 3rd degree heart blocks.
7.Any history of a second neoplasm except for curatively treated non melanoma skin cancer or carcinoma in situ of the cervix.
8.Concomitant treatment with other anticancer drugs.
9.Concomitant treatment with any other experimental drug.
10.Patients with not adequate haematological, hepatic and renal function.
11.Current known infection with HIV, HBV or HCV.
12.Any other serious illness or medical condition.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the overall Clinical Benefit (CB) of the two regimens (nab-paclitaxel plus trastuzumab (ARM A) versus nab-paclitaxel alone (ARM B)) among evaluable patients.;Secondary Objective: To determine the prognostic and predictive significance of HER2-positive CTC. <br>To evaluate additional measures of tumor control to further characterize the efficacy of the nab-paclitaxel plus trastuzumab vs. nab-paclitaxel. ;Primary end point(s): The evaluation of the overall CB among evaluable patients.;Timepoint(s) of evaluation of this end point: 24 weeks after treatment initiation

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •To evaluate the early response based on CTCs variations as a predictor of patients’ outcome;<br>•To validate the prognostic significance of HER2+ve CTCs in patients with primary HER2-ve MBC; <br>•To obtain RNA from EpCAM+ve CTC isolated from MBC patients using the Veridex® Profile kit for pharmacodynamic evaluation (HER2-neu, PI3K, PTEN, pAKT, mTOR).<br>•To determine HER2 expression, proliferation index in fine needle aspirate (FNA) biopsies (optional).<br>•To evaluate the prognostic and predictive role of circulating HER2 and EGFR.<br>•To evaluate the Progression Free Survival.<br>•To evaluate the Overall Survival.<br>•To determine patient’s tolerability and safety of the treatment.<br>•To evaluate the Quality of Life.<br>;Timepoint(s) of evaluation of this end point: 24 months from the end of last treatment of LSI.