A Phase I Dose Escalation Study With 99mTC - or 186 Re-labelled Humanised Monoclonal Antibody BIWA 4, in Patients With Head and Neck Cancer
Overview
- Phase
- Phase 1
- Intervention
- unlabelled hMAb BIWA 4 - medium dose
- Conditions
- Head and Neck Neoplasms
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 33
- Primary Endpoint
- MRT (Mean residence time)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
99mTc - labelled hMAb BIWA 4 - medium dose
Intervention: unlabelled hMAb BIWA 4 - medium dose
99mTc - labelled hMAb BIWA 4 - medium dose
Intervention: 99mTc - labelled hMAb BIWA 4
99mTc - labelled hMAb BIWA 4 - low dose
Intervention: 99mTc - labelled hMAb BIWA 4
99mTc - labelled hMAb BIWA 4 - low dose
Intervention: unlabelled hMAb BIWA 4 - low dose
99mTc - labelled hMAb BIWA 4 - high dose
Intervention: 99mTc - labelled hMAb BIWA 4
99mTc - labelled hMAb BIWA 4 - high dose
Intervention: unlabelled hMAb BIWA 4 - high dose
186 Re - labelled hMAb BIWA 4 - escalating dose
Intervention: 186 Re - labelled hMAb BIWA 4
Outcomes
Primary Outcomes
MRT (Mean residence time)
Time Frame: up to 336 hours after infusion
Occurence of dose limiting toxicities (DLT)
Time Frame: up to 144 hours post infusion
Presence of human-anti-human-antibody (HAHA)
Time Frame: after 144 hours post infusion
Immunoscintigraphic imaging evaluation (Parts A + B)
Time Frame: up to 21 hours after infusion
CL (Total body clearance)
Time Frame: up to 336 hours after infusion
Number of patients with abnormal changes in laboratory parameters
Time Frame: up to 6 weeks after infusion
Biodistribution of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples - Biopsy (Part A)
Time Frame: at 48 h after infusion
uptake expressed as percentage of the injected dose per kg tissue (%ID/kg)
Cmax (Maximum measured concentration of the analyte in plasma)
Time Frame: up to 336 hours after infusion
Vz (Apparent volume of distribution during the terminal phase)
Time Frame: up to 336 hours after infusion
Cumulative urinary excretion of radioactivity over time
Time Frame: up to 96 hours after infusion
Number of patients with adverse events
Time Frame: up to 10 weeks
Number of patients with clinically significant changes in vital signs
Time Frame: up to 6 weeks after infusion
t½ (Terminal half-life of the analyte in plasma)
Time Frame: up to 336 hours after infusion
Vss (Apparent volume of distribution under steady-state conditions)
Time Frame: up to 336 hours after infusion
Actual organ uptake of 99mTC-labelled hMAb BIWA 4
Time Frame: at 21 h after infusion
expressed as % I.D. (injected dose)
AUC0-∞ (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time Frame: up to 336 hours after infusion
tmax (Time from dosing to the maximum concentration of the analyte in plasma)
Time Frame: up to 336 hours after infusion
Uptake of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples (Part A)
Time Frame: up to 6 weeks after infusion
Assessment of biodistribution by radioimmunoscintigraphy expressed as low, medium or high
Secondary Outcomes
- Tumour response according to response criteria of the World Health Organisation (WHO)(up to 144 hours after infusion)
- Maximum tolerated radiation dose of 186Re-labelled hMAb BIWA 4(up to 144 hours after infusion)