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

Head and Neck Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02204033
• Other study ID #: 1170.1
• Status: Completed
• Phase: Phase 1
• First received: July 29, 2014
• Last updated: July 29, 2014
• Start date: March 1999

Study information

• Verified date: July 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Ministry of Health, Welfare and Sport
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. primary completion date: June 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Neoplasms

Intervention

Drug:
• 99mTc - labelled hMAb BIWA 4

• 186 Re - labelled hMAb BIWA 4

• unlabelled hMAb BIWA 4 - low dose

• unlabelled hMAb BIWA 4 - medium dose

• unlabelled hMAb BIWA 4 - high dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with adverse events		up to 10 weeks	No
Primary	Presence of human-anti-human-antibody (HAHA)		after 144 hours post infusion	No
Primary	Number of patients with clinically significant changes in vital signs		up to 6 weeks after infusion	No
Primary	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	No
Primary	Immunoscintigraphic imaging evaluation (Parts A + B)		up to 21 hours after infusion	No
Primary	AUC0-8 (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	No
Primary	Cmax (Maximum measured concentration of the analyte in plasma)		up to 336 hours after infusion	No
Primary	tmax (Time from dosing to the maximum concentration of the analyte in plasma)		up to 336 hours after infusion	No
Primary	t½ (Terminal half-life of the analyte in plasma)		up to 336 hours after infusion	No
Primary	Vz (Apparent volume of distribution during the terminal phase)		up to 336 hours after infusion	No
Primary	Vss (Apparent volume of distribution under steady-state conditions)		up to 336 hours after infusion	No
Primary	CL (Total body clearance)		up to 336 hours after infusion	No
Primary	MRT (Mean residence time)		up to 336 hours after infusion	No
Primary	Cumulative urinary excretion of radioactivity over time		up to 96 hours after infusion	No
Primary	Number of patients with abnormal changes in laboratory parameters		up to 6 weeks after infusion	No
Primary	Occurence of dose limiting toxicities (DLT)		up to 144 hours post infusion	No
Primary	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	No
Primary	Actual organ uptake of 99mTC-labelled hMAb BIWA 4	expressed as % I.D. (injected dose)	at 21 h after infusion	No
Secondary	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	No
Secondary	Maximum tolerated radiation dose of 186Re-labelled hMAb BIWA 4		up to 144 hours after infusion	No

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