Back to resultsDose Escalation Study With 99mTC - or 186 Re-labelled Humanised Monoclonal Antibody (hMAb) BIWA 4 in Patients With Head and Neck Cancer
Primary Purpose
Head and Neck Neoplasms
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
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
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Neoplasms
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
99mTc - labelled hMAb BIWA 4 - low dose
99mTc - labelled hMAb BIWA 4 - medium dose
99mTc - labelled hMAb BIWA 4 - high dose
186 Re - labelled hMAb BIWA 4 - escalating dose
Arm Description
Outcomes
Primary Outcome Measures
Number of patients with adverse events
Presence of human-anti-human-antibody (HAHA)
Number of patients with clinically significant changes in vital signs
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)
Immunoscintigraphic imaging evaluation (Parts A + B)
AUC0-∞ (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Cmax (Maximum measured concentration of the analyte in plasma)
tmax (Time from dosing to the maximum concentration of the analyte in plasma)
t½ (Terminal half-life of the analyte in plasma)
Vz (Apparent volume of distribution during the terminal phase)
Vss (Apparent volume of distribution under steady-state conditions)
CL (Total body clearance)
MRT (Mean residence time)
Cumulative urinary excretion of radioactivity over time
Number of patients with abnormal changes in laboratory parameters
Occurence of dose limiting toxicities (DLT)
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
Actual organ uptake of 99mTC-labelled hMAb BIWA 4
expressed as % I.D. (injected dose)
Secondary Outcome Measures
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
Maximum tolerated radiation dose of 186Re-labelled hMAb BIWA 4
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02204033
Brief Title
Dose Escalation Study With 99mTC - or 186 Re-labelled Humanised Monoclonal Antibody (hMAb) BIWA 4 in Patients With Head and Neck Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
March 1999 (undefined)
Primary Completion Date
June 2001 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
99mTc - labelled hMAb BIWA 4 - low dose
Arm Type
Experimental
Arm Title
99mTc - labelled hMAb BIWA 4 - medium dose
Arm Type
Experimental
Arm Title
99mTc - labelled hMAb BIWA 4 - high dose
Arm Type
Experimental
Arm Title
186 Re - labelled hMAb BIWA 4 - escalating dose
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
99mTc - labelled hMAb BIWA 4
Intervention Type
Drug
Intervention Name(s)
186 Re - labelled hMAb BIWA 4
Intervention Type
Drug
Intervention Name(s)
unlabelled hMAb BIWA 4 - low dose
Intervention Type
Drug
Intervention Name(s)
unlabelled hMAb BIWA 4 - medium dose
Intervention Type
Drug
Intervention Name(s)
unlabelled hMAb BIWA 4 - high dose
Primary Outcome Measure Information:
Title
Number of patients with adverse events
Time Frame
up to 10 weeks
Title
Presence of human-anti-human-antibody (HAHA)
Time Frame
after 144 hours post infusion
Title
Number of patients with clinically significant changes in vital signs
Time Frame
up to 6 weeks after infusion
Title
Biodistribution of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples - Biopsy (Part A)
Description
uptake expressed as percentage of the injected dose per kg tissue (%ID/kg)
Time Frame
at 48 h after infusion
Title
Immunoscintigraphic imaging evaluation (Parts A + B)
Time Frame
up to 21 hours after infusion
Title
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
Title
Cmax (Maximum measured concentration of the analyte in plasma)
Time Frame
up to 336 hours after infusion
Title
tmax (Time from dosing to the maximum concentration of the analyte in plasma)
Time Frame
up to 336 hours after infusion
Title
t½ (Terminal half-life of the analyte in plasma)
Time Frame
up to 336 hours after infusion
Title
Vz (Apparent volume of distribution during the terminal phase)
Time Frame
up to 336 hours after infusion
Title
Vss (Apparent volume of distribution under steady-state conditions)
Time Frame
up to 336 hours after infusion
Title
CL (Total body clearance)
Time Frame
up to 336 hours after infusion
Title
MRT (Mean residence time)
Time Frame
up to 336 hours after infusion
Title
Cumulative urinary excretion of radioactivity over time
Time Frame
up to 96 hours after infusion
Title
Number of patients with abnormal changes in laboratory parameters
Time Frame
up to 6 weeks after infusion
Title
Occurence of dose limiting toxicities (DLT)
Time Frame
up to 144 hours post infusion
Title
Uptake of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples (Part A)
Description
Assessment of biodistribution by radioimmunoscintigraphy expressed as low, medium or high
Time Frame
up to 6 weeks after infusion
Title
Actual organ uptake of 99mTC-labelled hMAb BIWA 4
Description
expressed as % I.D. (injected dose)
Time Frame
at 21 h after infusion
Secondary Outcome Measure Information:
Title
Tumour response according to response criteria of the World Health Organisation (WHO)
Description
assessed by Computer Tomography (CT) and/or by Magnet resonance imaging (MRI) and/or bone scintigraphy and/or by physical examination
Time Frame
up to 144 hours after infusion
Title
Maximum tolerated radiation dose of 186Re-labelled hMAb BIWA 4
Time Frame
up to 144 hours after infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
Related Info
Learn more about this trial
Dose Escalation Study With 99mTC - or 186 Re-labelled Humanised Monoclonal Antibody (hMAb) BIWA 4 in Patients With Head and Neck Cancer
We'll reach out to this number within 24 hrs