Clinical trial NCT02204033: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Head and Neck Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-30
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: up to 10 weeks
measure: Presence of human-anti-human-antibody (HAHA)
timeFrame: after 144 hours post infusion
measure: Number of patients with clinically significant changes in vital signs
timeFrame: up to 6 weeks after infusion
measure: Biodistribution of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples - Biopsy (Part A)
timeFrame: at 48 h after infusion
measure: Immunoscintigraphic imaging evaluation (Parts A + B)
timeFrame: up to 21 hours after infusion
measure: AUC0-∞ (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: up to 336 hours after infusion
measure: Cmax (Maximum measured concentration of the analyte in plasma)
timeFrame: up to 336 hours after infusion
measure: tmax (Time from dosing to the maximum concentration of the analyte in plasma)
timeFrame: up to 336 hours after infusion
measure: t½ (Terminal half-life of the analyte in plasma)
timeFrame: up to 336 hours after infusion
measure: Vz (Apparent volume of distribution during the terminal phase)
timeFrame: up to 336 hours after infusion
measure: Vss (Apparent volume of distribution under steady-state conditions)
timeFrame: up to 336 hours after infusion
measure: CL (Total body clearance)
timeFrame: up to 336 hours after infusion
measure: MRT (Mean residence time)
timeFrame: up to 336 hours after infusion
measure: Cumulative urinary excretion of radioactivity over time
timeFrame: up to 96 hours after infusion
measure: Number of patients with abnormal changes in laboratory parameters
timeFrame: up to 6 weeks after infusion
measure: Occurence of dose limiting toxicities (DLT)
timeFrame: up to 144 hours post infusion
measure: Uptake of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples (Part A)
timeFrame: up to 6 weeks after infusion
measure: Actual organ uptake of 99mTC-labelled hMAb BIWA 4
timeFrame: at 21 h after infusion
Secondary outcomes:
measure: Tumour response according to response criteria of the World Health Organisation (WHO)
timeFrame: up to 144 hours after infusion
measure: Maximum tolerated radiation dose of 186Re-labelled hMAb BIWA 4
timeFrame: up to 144 hours after infusion
Other outcomes:
Locations:
Study officials:
References: