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

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Head and Neck Neoplasms

Treatments: Drug: unlabelled hMAb BIWA 4 - medium dose; Drug: 99mTc - labelled hMAb BIWA 4; Drug: unlabelled hMAb BIWA 4 - high dose; Drug: unlabelled hMAb BIWA 4 - low dose; Drug: 186 Re - labelled hMAb BIWA 4

Study type: Interventional

Funder types: Industry

Identifiers

NCT02204033

1170.1

Details and patient eligibility

About

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.

Enrollment: 33 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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33 participants in 4 patient groups

99mTc - labelled hMAb BIWA 4 - low dose

Experimental group

Treatment:

Drug: 99mTc - labelled hMAb BIWA 4

Drug: unlabelled hMAb BIWA 4 - low dose

99mTc - labelled hMAb BIWA 4 - medium dose

Experimental group

Treatment:

Drug: unlabelled hMAb BIWA 4 - medium dose

Drug: 99mTc - labelled hMAb BIWA 4

99mTc - labelled hMAb BIWA 4 - high dose

Experimental group

Treatment:

Drug: unlabelled hMAb BIWA 4 - high dose

Drug: 99mTc - labelled hMAb BIWA 4

186 Re - labelled hMAb BIWA 4 - escalating dose

Experimental group

Treatment:

Drug: 186 Re - labelled hMAb BIWA 4