Biodistribution Study With 186 Re-labelled Humanised Monoclonal Antibody BIWA 4 in Patients With Adenocarcinoma of the Breast

Study Overview
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Brief Summary
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The primary objectives of this study were to assess the safety and tolerability of intravenously (i.v.) administered 186Rhenium (186Re)-labelled bivatuzumab and to investigate the biodistribution and pharmacokinetics of 186Re-labelled bivatuzumab in patients with adenocarcinoma of the breast

Official Title
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A Phase I Biodistribution Study With 186 Re-labelled Humanised Monoclonal Antibody BIWA 4, in Patients With Adenocarcinoma of the Breast

Conditions
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Adenocarcinoma

Intervention / Treatment
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* Drug: BIWA 4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histological or cytological confirmation of a primary adenocarcinoma of the breast Patients destined for tumour extirpation or mastectomy 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 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 or radiotherapy had to be known Hematological disorders, congestive heart failure, bronchial asthma, alimentary or contact allergy, severe atopy or allergy

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events |  | up to 6 weeks after infusion | 
| Number of patients with abnormal changes in laboratory parameters |  | up to 6 weeks after infusion | 
| Number of patients with clinically significant changes in vital signs |  | up to 6 weeks after infusion | 
| Presence of Human-Anti-Human-Antibody (HAHA) |  | up to 6 weeks after infusion | 
| Uptake of 186Re-labelled hMAb BIWA 4 in tumour and normal tissue samples | Assessment of biodistribution by radioscintigraphy expressed as low, medium or high | up to 72 hours after infusion | 
| AUC0-∞ (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | up to 240 hours after infusion | 
| Cmax (Maximum measured concentration of the analyte in plasma) |  | up to 240 hours after infusion | 
| tmax (Time from dosing to the maximum concentration of the analyte in plasma) |  | up to 240 hours after infusion | 
| t½ (Terminal half-life of the analyte in plasma) |  | up to 240 hours after infusion | 
| MRT (Mean residence time of the analyte in the body) |  | up to 240 hours after infusion | 
| Vss (Apparent volume of distribution under steady state conditions) |  | up to 240 hours after infusion | 
| Vz (Apparent volume of distribution during the terminal phase) |  | up to 240 hours after infusion | 
| CL (Total body clearance) |  | up to 240 hours after infusion | 
| Actual uptake of 186Re-labelled hMAb BIWA 4 in tumour and normal tissue samples | expressed as %ID/kg | at 72 hours after 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 |