Head and Neck Neoplasms
Conditions
Brief summary
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.
Interventions
DRUG99mTc - labelled hMAb BIWA 4
DRUG186 Re - labelled hMAb BIWA 4
DRUGunlabelled hMAb BIWA 4 - low dose
DRUGunlabelled hMAb BIWA 4 - medium dose
DRUGunlabelled hMAb BIWA 4 - high dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with histological confirmation of squamous cell carcinoma in the head and neck * Patients destined for surgery by means of neck dissection (Part A) or : * Patients with either local and/or regional recurrent disease for which curative treatment options were not available or distant metastases. The tumor deposits had to be measurable either clinically or by one or more radiological technique (s) (CT, MRI, bone scintigraphy). Because RIT was expected to be more effective in smaller size tumor deposits, patients with lesions measuring \> 3 cm in greatest dimension were preferred (Part B) * 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, (nor 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Actual organ uptake of 99mTC-labelled hMAb BIWA 4 | at 21 h after infusion | expressed as % I.D. (injected dose) |
| 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) | up to 6 weeks after infusion | Assessment of biodistribution by radioimmunoscintigraphy expressed as low, medium or high |
| t½ (Terminal half-life of the analyte in plasma) | up to 336 hours after infusion | — |
| Vz (Apparent volume of distribution during the terminal phase) | up to 336 hours after infusion | — |
| Vss (Apparent volume of distribution under steady-state conditions) | 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 | — |
| 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) | at 48 h after infusion | uptake expressed as percentage of the injected dose per kg tissue (%ID/kg) |
| 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 | — |
| 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated radiation dose of 186Re-labelled hMAb BIWA 4 | up to 144 hours after infusion | — |
| Tumour response according to response criteria of the World Health Organisation (WHO) | up to 144 hours after infusion | assessed by Computer Tomography (CT) and/or by Magnet resonance imaging (MRI) and/or bone scintigraphy and/or by physical examination |
Outcome results
None listed