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

NCT02204033 | Completed Phase 1

• 1 other identifier: 1170.1
• Study Type: interventional
• Target: 33
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Head and Neck Neoplasms

Outcome Measures

Primary Outcomes (18)

• 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 Outcomes (2)

• 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

Study Arms (4)

99mTc - labelled hMAb BIWA 4 - low dose

EXPERIMENTAL

Drug: 99mTc - labelled hMAb BIWA 4; Drug: unlabelled hMAb BIWA 4 - low dose

99mTc - labelled hMAb BIWA 4 - medium dose

EXPERIMENTAL

Drug: 99mTc - labelled hMAb BIWA 4; Drug: unlabelled hMAb BIWA 4 - medium dose

99mTc - labelled hMAb BIWA 4 - high dose

EXPERIMENTAL

Drug: 99mTc - labelled hMAb BIWA 4; Drug: unlabelled hMAb BIWA 4 - high dose

186 Re - labelled hMAb BIWA 4 - escalating dose

EXPERIMENTAL

Drug: 186 Re - labelled hMAb BIWA 4

Interventions

99mTc - labelled hMAb BIWA 4 DRUG

99mTc - labelled hMAb BIWA 4 - high dose; 99mTc - labelled hMAb BIWA 4 - low dose; 99mTc - labelled hMAb BIWA 4 - medium dose

186 Re - labelled hMAb BIWA 4 DRUG

186 Re - labelled hMAb BIWA 4 - escalating dose

unlabelled hMAb BIWA 4 - low dose DRUG

99mTc - labelled hMAb BIWA 4 - low dose

unlabelled hMAb BIWA 4 - medium dose DRUG

99mTc - labelled hMAb BIWA 4 - medium dose

unlabelled hMAb BIWA 4 - high dose DRUG

99mTc - labelled hMAb BIWA 4 - high dose

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2014
• First Posted: July 30, 2014
• Study Start: March 1, 1999
• Primary Completion: June 1, 2001
• Last Updated: July 30, 2014

Record last verified: 2014-07