Single Dose Escalation Study of Bivatuzumab Mertansine in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck

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

Official Title
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An Open Phase I Single Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck With Repeated Administration in Patients With Clinical Benefit

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Drug: bivatuzumab mertansine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male and female patients aged 18 years or older patients with histologically confirmed squamous cell carcinoma of the head and neck patients with local and / or regional recurrent disease or distant metastases who are refractory to 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 of 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 neuropathy grade 2 or above (excluding pre-existing neuropathy of cranial nerves due to surgery, radiotherapy or tumour growth) 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 three weeks prior to treatment with the trial drug or during the trial radiotherapy to head and neck region within the past four weeks before inclusion or during the trial men and 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 three weeks before start of therapy or concomitantly with this trial patients unable to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| Number of patients with adverse events | grading according to the common toxicity criteria (CTC) | up to day 21 | 
| Number of patients with clinically significant changes in laboratory parameters |  | up to day 21 | 
| Number of patients with clinically significant changes in vital signs |  | up to day 21 | 
| Tumor response | according to the 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 |