Single Dose Escalation Study of Bivatuzumab Mertansine in Female Patients With CD44v6 Positive Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
Maximum tolerated dose (MTD), safety, pharmacokinetics, efficacy of bivatuzumab mertansine

Official Title
-----------------
An Open Phase I Single Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously in Female Patients With CD44v6 Positive Metastatic Breast Cancer With Repeated Administration in Patients With Clinical Benefit

Conditions
-----------------
Breast Neoplasms

Intervention / Treatment
-----------------
* Drug: bivatuzumab mertansine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: female patients aged 18 years or older patients with breast cancer positive for CD44v6 in at least 50 % of the tumour cells patients with metastases pretreated with anthracyclines and taxanes (unless contraindications to taxanes and / or anthracyclines) or not amenable to established treatments measurable tumour deposits by one or more radiological techniques (MRI, CT) life expectancy of at least 6 months Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2 patients must have given written informed consent (which must be consistent with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation) Exclusion Criteria: hypersensitivity to humanised or murine antibodies, immunoconjugates or the excipients of the trial drugs known secondary malignancy requiring therapy active infectious disease brain metastases requiring therapy neuropathy common toxicity criteria (CTC) grade 2 or above absolute neutrophil count less than 1,500/mm3 platelet count less than 100,000/mm3 bilirubin greater than 1.5 mg/dl (> 26 μmol/L, système internationale (SI) unit equivalent) aspartate amino transferase (AST) and/or alanine amino transferase (ALT) greater than 3 times the upper limit of normal serum creatinine greater than 1.5 mg/dl (> 132 μmol/L, SI unit equivalent) concomitant non-oncological diseases which are considered relevant for the evaluation of the safety of the trial drug chemo- or immunotherapy within the past four weeks prior to treatment with the trial drug or during the trial (except for present trial drug) radiotherapy to breast and thorax region within the past four weeks before inclusion or during the trial women who are sexually active and unwilling to use a medically acceptable method of contraception pregnancy or lactation treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug) patients unable to comply with the protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single dose escalation<br> | Drug: bivatuzumab mertansine<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) of bivatuzumab mertansine |  | up to day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | up to day 21 | 
| Number of patients with clinically significant findings in laboratory tests |  | up to day 21 | 
| Number of patients with clinically significant findings in vital signs |  | up to day 21 | 
| Tumor response rate | assessed by response evaluation criteria in solid tumours (RECIST) | up to 1 year | 
| Concentration of bivatuzumab mertansine |  | up to day 21 | 
| Concentration of CD44v6 recognising IgG antibodies (anti-CD44v6-IgG) |  | up to day 21 | 
| Number of patients with development of human anti-human antibodies (HAHA) |  | up to day 21 |