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The general aim of the present study was to assess the safety and tolerability of intravenously administered Technetium 99m (99mTc) and Rhenium-186 radionuclide (186 Re) -labelled hMAb BIWA 4, to confirm preferential accumulation in the tumour of 99mTc - labelled hMAb BIWA 4, to determine the maximum tolerated radiation dose of 186 Re-labelled hMAb BIWA 4 and to propose a safety dose for phase II development.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 99mTc - labelled hMAb BIWA 4 - low dose | Experimental |
| |
| 99mTc - labelled hMAb BIWA 4 - medium dose | Experimental |
| |
| 99mTc - labelled hMAb BIWA 4 - high dose | Experimental |
| |
| 186 Re - labelled hMAb BIWA 4 - escalating dose | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 99mTc - labelled hMAb BIWA 4 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with adverse events | up to 10 weeks | |
| Presence of human-anti-human-antibody (HAHA) | after 144 hours post infusion | |
| Number of patients with clinically significant changes in vital signs | up to 6 weeks after infusion | |
| Biodistribution of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples - Biopsy (Part A) | uptake expressed as percentage of the injected dose per kg tissue (%ID/kg) | at 48 h after infusion |
| Immunoscintigraphic imaging evaluation (Parts A + B) | up to 21 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 336 hours after infusion | |
| Cmax (Maximum measured concentration of the analyte in plasma) | up to 336 hours after infusion | |
| tmax (Time from dosing to the maximum concentration of the analyte in plasma) | up to 336 hours after infusion | |
| t½ (Terminal half-life of the analyte in plasma) | up to 336 hours after infusion | |
| Vz (Apparent volume of distribution during the terminal phase) |
| Measure | Description | Time Frame |
|---|---|---|
| Tumour response according to response criteria of the World Health Organisation (WHO) | assessed by Computer Tomography (CT) and/or by Magnet resonance imaging (MRI) and/or bone scintigraphy and/or by physical examination | up to 144 hours after infusion |
| Maximum tolerated radiation dose of 186Re-labelled hMAb BIWA 4 |
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Inclusion Criteria:
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)
Women with a positive serum pregnancy test at baseline
Chemotherapy or radiotherapy within 4 weeks before inclusion in the study
White blood cell count < 3000/mm³, granulocyte count < 1500/mm³ or platelet count < 100000/mm³
Hematological disorders, congestive heart failure, bronchial asthma, alimentary or contact allergy, severe atopy or allergy
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| 186 Re - labelled hMAb BIWA 4 | Drug |
|
| unlabelled hMAb BIWA 4 - low dose | Drug |
|
| unlabelled hMAb BIWA 4 - medium dose | Drug |
|
| unlabelled hMAb BIWA 4 - high dose | Drug |
|
| up to 336 hours after infusion |
| Vss (Apparent volume of distribution under steady-state conditions) | up to 336 hours after infusion |
| CL (Total body clearance) | up to 336 hours after infusion |
| MRT (Mean residence time) | up to 336 hours after infusion |
| Cumulative urinary excretion of radioactivity over time | up to 96 hours after infusion |
| Number of patients with abnormal changes in laboratory parameters | up to 6 weeks after infusion |
| Occurence of dose limiting toxicities (DLT) | up to 144 hours post infusion |
| Uptake of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples (Part A) | Assessment of biodistribution by radioimmunoscintigraphy expressed as low, medium or high | up to 6 weeks after infusion |
| Actual organ uptake of 99mTC-labelled hMAb BIWA 4 | expressed as % I.D. (injected dose) | at 21 h after infusion |
| up to 144 hours after infusion |
| ID | Term |
|---|---|
| D006258 | Head and Neck Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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