Dose Escalation Study With 99mTC - or 186 Re-labelled Humanised Monoclonal Antibody (hMAb) BIWA 4 in Patients With Head and Neck Cancer

A Phase I Dose Escalation Study With 99mTC - or 186 Re-labelled Humanised Monoclonal Antibody BIWA 4, in Patients With Head and Neck Cancer

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Neoplasms
• Intervention / Treatment: Drug: 99mTc - 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: 186 Re - labelled hMAb BIWA 4

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 99mTc - labelled hMAb BIWA 4 - low dose	Drug: 99mTc - labelled hMAb BIWA 4; Drug: unlabelled hMAb BIWA 4 - low dose
Experimental: 99mTc - labelled hMAb BIWA 4 - medium dose	Drug: 99mTc - labelled hMAb BIWA 4; Drug: unlabelled hMAb BIWA 4 - medium dose
Experimental: 99mTc - labelled hMAb BIWA 4 - high dose	Drug: 99mTc - labelled hMAb BIWA 4; Drug: unlabelled hMAb BIWA 4 - high dose
Experimental: 186 Re - labelled hMAb BIWA 4 - escalating dose	Drug: 186 Re - labelled hMAb BIWA 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)		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

Secondary Outcome Measures

Outcome Measure	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		up to 144 hours after infusion

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 1999
• Primary Completion (Actual): June 1, 2001

Study Registration Dates

• First Submitted: July 29, 2014
• First Submitted That Met QC Criteria: July 29, 2014
• First Posted (Estimate): July 30, 2014

Study Record Updates

• Last Update Posted (Estimate): July 30, 2014
• Last Update Submitted That Met QC Criteria: July 29, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms
• Other Study ID Numbers: 1170.1