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

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 Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously Once Per Week for Three Weeks in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck or Esophagus With Repeated Administration Courses in Patients With Clinical Benefit

Conditions
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Carcinoma, Squamous Cell

Intervention / Treatment
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* Drug: bivatuzumab mertansine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients from 18 to 80 years of age (both inclusive) patients with histologically confirmed squamous cell carcinoma of the head and neck or esophagus patients with local and / or regional recurrent disease or distant metastases who are refractory to or not amenable to established treatments evaluable tumour deposits life expectancy of at least 3 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 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-, radio- or immunotherapy within the past four weeks prior to treatment with the trial drug or during the trial (except for present trial drug) 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 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
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Minimum Age: 18 Years
Maximum Age: 80 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>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) |  | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | graded according to common toxicity criteria (CTC) | up to 14 days after last drug administration | 
| Number of patients with clinically significant findings in laboratory examinations |  | up to 14 days after last drug administration | 
| Number of patients with clinically significant findings in vital signs |  | up to 14 days after last drug administration | 
| Number of patients with development of Human Anti-Human Antibody (HAHA) |  | up to 14 days after last drug administration | 
| Area under the serum concentration time curve from time zero to time point 168 hours (AUC0-168) |  | up to 168 hours | 
| Area under the serum concentration time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz) |  | up to 14 days after last drug administration | 
| Area under the serum concentration time curve from time point zero to infinity (AUC0-∞) |  | up to 14 days after last drug administration | 
| Maximum serum concentration (Cmax) |  | up to 14 days after last drug administration | 
| Time to reach maximum serum concentration (tmax) |  | up to 14 days after last drug administration | 
| Terminal elimination half-life (t1/2) |  | up to 14 days after last drug administration | 
| Mean residence time (MRT) |  | up to 14 days after last drug administration | 
| Total body clearance (CL) |  | up to 14 days after last drug administration | 
| Volume of distribution at steady state (Vss) |  | up to 14 days after last drug administration | 
| Volume of distribution during the terminal elimination phase (Vz) |  | up to 14 days after last drug administration | 
| Trough concentration at steady state (Cpre,ss) |  | up to 7 days after drug administration | 
| Minimum serum concentration during the dosing interval τ at steady state (Cmin,ss) |  | up to 7 days after drug administration | 
| Linearity index (LI) |  | up to 14 days after last drug administration | 
| Accumulation factor (RA) |  | up to 14 days after last drug administration | 
| Tumor response | according to response evaluation criteria in solid tumours (RECIST) | up to 14 days after last drug administration |