A Phase I Dose Escalation Study With 99mTC - or 186 Re-labelled Humanised Monoclonal Antibody BIWA 4, in Patients With Head and Neck Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 主要终点
- MRT (Mean residence time)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
99mTc - labelled hMAb BIWA 4 - medium dose
干预措施: unlabelled hMAb BIWA 4 - medium dose (Drug)
99mTc - labelled hMAb BIWA 4 - medium dose
干预措施: 99mTc - labelled hMAb BIWA 4 (Drug)
99mTc - labelled hMAb BIWA 4 - low dose
干预措施: 99mTc - labelled hMAb BIWA 4 (Drug)
99mTc - labelled hMAb BIWA 4 - low dose
干预措施: unlabelled hMAb BIWA 4 - low dose (Drug)
99mTc - labelled hMAb BIWA 4 - high dose
干预措施: 99mTc - labelled hMAb BIWA 4 (Drug)
99mTc - labelled hMAb BIWA 4 - high dose
干预措施: unlabelled hMAb BIWA 4 - high dose (Drug)
186 Re - labelled hMAb BIWA 4 - escalating dose
干预措施: 186 Re - labelled hMAb BIWA 4 (Drug)
结局指标
主要结局
MRT (Mean residence time)
时间窗: up to 336 hours after infusion
Occurence of dose limiting toxicities (DLT)
时间窗: up to 144 hours post infusion
Presence of human-anti-human-antibody (HAHA)
时间窗: after 144 hours post infusion
Immunoscintigraphic imaging evaluation (Parts A + B)
时间窗: up to 21 hours after infusion
CL (Total body clearance)
时间窗: up to 336 hours after infusion
Number of patients with abnormal changes in laboratory parameters
时间窗: up to 6 weeks after infusion
Biodistribution of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples - Biopsy (Part A)
时间窗: at 48 h after infusion
uptake expressed as percentage of the injected dose per kg tissue (%ID/kg)
Cmax (Maximum measured concentration of the analyte in plasma)
时间窗: up to 336 hours after infusion
Vz (Apparent volume of distribution during the terminal phase)
时间窗: up to 336 hours after infusion
Cumulative urinary excretion of radioactivity over time
时间窗: up to 96 hours after infusion
Number of patients with adverse events
时间窗: up to 10 weeks
Number of patients with clinically significant changes in vital signs
时间窗: up to 6 weeks after infusion
t½ (Terminal half-life of the analyte in plasma)
时间窗: up to 336 hours after infusion
Vss (Apparent volume of distribution under steady-state conditions)
时间窗: up to 336 hours after infusion
Actual organ uptake of 99mTC-labelled hMAb BIWA 4
时间窗: at 21 h after infusion
expressed as % I.D. (injected dose)
AUC0-∞ (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
时间窗: up to 336 hours after infusion
tmax (Time from dosing to the maximum concentration of the analyte in plasma)
时间窗: up to 336 hours after infusion
Uptake of 99mTC-labelled hMAb BIWA 4 in tumour and normal tissue samples (Part A)
时间窗: up to 6 weeks after infusion
Assessment of biodistribution by radioimmunoscintigraphy expressed as low, medium or high
次要结局
- 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)