Biodistribution Study With 186 Re-labelled Humanised Monoclonal Antibody BIWA 4 in Patients With Non-small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The primary objectives of this study is to assess the safety and tolerability of intravenously (i.v.) administered 186 Rhenium-isotope (186Re)-labelled bivatuzumab and to investigate the biodistribution and pharmacokinetics of 186 Re-labelled bivatuzumab in patients with non-small cell lung cancer (NSCLC)

Official Title
-----------------
A Phase I Biodistribution Study With 186 Re-labelled Humanised Monoclonal Antibody BIWA 4, in Patients With Non-small Cell Lung Cancer

Conditions
-----------------
Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
-----------------
* Drug: hMAb BIWA 4


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have histological or cytological confirmation of Non small cell lung cancer (NSCLC) stage I, II or IIIa according to the staging system of the American Joint Committee on Cancer (AJCC) Patients destined for resection of the tumour Patients over 18 years of age Patients younger than 80 years of age Patients who had given 'written informed consent' Patients with a life expectancy of at least 3 months Patients with a good performance status: Karnofsky > 60 Exclusion Criteria: Life-threatening infection, allergic diathesis, organ failure (bilirubin > 30µmol/l and/or creatinine > 150 µmol/l) or evidence of a recent myocardial infarction on Electrocardiogram (ECG) or unstable angina pectoris Pre-menopausal women (last menstruation <= 1 year prior to study start) Not surgically sterile (hysterectomy, tubal ligation) and Not practicing acceptable means of birth control, (or not planned to be continued throughout the study). Acceptable methods of birth control include oral, implantable or injectable contraceptives Women with a positive serum pregnancy test at baseline White blood cell count < 3000/mm³, granulocyte count < 1500/mm³ or platelet count < 100000/mm³. Details of prior chemotherapy and radiotherapy had to be known. Hematological disorders, congestive heart failure, bronchial asthma, alimentary or contact allergy, severe atopy or allergy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hMAb BIWA 4<br>Bivatuzumab: 186 Re-labelled humanised monoclonal antibody BIWA 4 | Drug: hMAb BIWA 4<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events |  | up to 6 weeks post infusion | 
| Number of patients with abnormal changes in laboratory parameters |  | up to 6 weeks post infusion | 
| Number of patients with clinically significant changes in vital signs |  | up to 6 weeks post infusion | 
| Presence of Human-Anti-Human-Antibody (HAHA) |  | up to 6 weeks post infusion | 
| Biodistribution of 186Re-labelled hMAb BIWA 4 in tumour and normal tissue samples | assessed by radioimmunoscintigraphy expressed as no, low, medium or high | up to 96 hours post infusion | 
| Uptake of 186Re-labelled hMAb BIWA 4 in tumour and normal tissue samples | Biodistribution assessed from biopsy sample as percentage of the injected dose per kg tissue (%ID/kg) | after surgery on day 8 | 
| AUC0-∞ (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | up to 6 weeks post infusion | 
| Cmax (Maximum measured concentration of the analyte in plasma) |  | up to 6 weeks post infusion | 
| tmax (Time from dosing to the maximum concentration of the analyte in plasma) |  | up to 6 weeks post infusion | 
| t½ (Terminal half-life of the analyte in plasma) |  | up to 6 weeks post infusion | 
| MRT (Mean residence time of the analyte in the body) |  | up to 6 weeks post infusion | 
| Vss (Apparent volume of distribution under steady state conditions) |  | up to 6 weeks post infusion | 
| Vz (Apparent volume of distribution during the terminal phase) |  | up to 6 weeks post infusion | 
| CL (Total body clearance) |  | up to 6 weeks post infusion |