A Radiopharmacokinetic and Radiodosimetric Phase I/II Imaging Study of 1-alpha-D-(5-[131I]Iodo-5-deoxyarabinofuranosyl)-2-Nitroimidazole (131I-IAZA) in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Change in hematology/SMA-12 serum biochemistry after [131]I-IAZA injection (first 10 patients)
研究概览
简要总结
Hypoxic cells in tumors have less oxygen than normal cells do, which leads to several changes inside the cells that lead to genetic chages making these cells resistant to treatment. The end result of this is increased tumor growth, spread of the tumor and poor outcome. Early studies have shown that [131]I-IAZA scans can help detect if there are hypoxic cells in the tumor. A [131]I-IAZA scan is a nuclear medicine test used to create pictures of the whole body after [131]I-IAZA is injected into a vein. Further scientific research will help understand how [131]I-IAZA is distributed throughout the body and how it can be used to treat hypoxic tumor cells.
The purpose of this study is to :
- Demonstrate the safety of [131]I-IAZA
- To Determine the biodistribution and tumor avidity of [131]I-IAZA in patients with locally advanced or metastatic solid tumors.
- To determine the optimal imaging time of [131]I-IAZA SPECT.
- To collect data from imaging and plasma sampling for radiopharmacokinetic analysis of [131]I-IAZA.
- To determine whole body dosimetry of [131]I-IAZA in selected patients.
- To evaluate tumor dosimetry of [131]I-IAZA in patients with positive uptake.
- To determine the radiation dose accrued in hypoxic tumors.
详细描述
The proposed clinical trial will be a Phase I/II open-label, single site, radiopharmacokinetic and radiodosimetric study in participants with locally advanced or metastatic solid tumors. All participants will be administered oral potassium iodide tablets to block radioactive iodine uptake in the thyroid. After administration of 185 MBq [131]I-IAZA (range: 150 - 220 MBq), all participants will undergo a series of up to six whole body planar scans on a dual headed gamma camera, and blood sampling for radiopharmacokinetic evaluation. A single fecal sample will be collected for up to 5 participants 24 - 72 hours post-injection, if possible, and assessed for total radioactivity. A safety evaluation will be conducted on the first 10 consecutively enrolled participants (safety sub-group), consisting of: Thyroid stimulating hormone (TSH) pre-injection and 6 weeks ±1 week post-injection; vital signs pre-injection and after scans 3 and 4; haematology, and SMA-12 serum biochemistry profile pre-injection and after scans 3 and 4; and an AE assessment at each imaging time point, up to 8 days post-injection. The safety evaluation for the remaining participants will consist of an AE assessment at each imaging time point, up to 8 days post-injection of [131]I-IAZA.
The radiodosimetry of [131]I-IAZA in different tissues will be determined in the first 5 consecutively enrolled participants from the planar images and the measured radioactivity in the fecal samples, if available. SPECT/CT imaging of the tumor(s) will be acquired at 19-36 hours post-injection for all the participants and will be used along with the planar images to determine the radiodosimetry and pattern of dose distribution within the tumor(s). Dosimetry data will be potentially correlated with the participants' health status, or other relevant information, as applicable .
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥18 and ≤ 75 years of age;
- •Subjects with locally advanced or metastatic solid tumors with at least one lesion evaluable by CT or magnetic resonance imaging (MRI) of at least 1 cm (smallest diameter), as measured by Response Evaluation Criteria In Solid Tumors (RECIST) within 12 weeks of enrolment;
- •Liver function tests (total bilirubin, alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase) ≤ 5 times the upper limit of normal measured within 2 weeks of enrolment. Serum albumin ≥ 23 g/L within 2 weeks of enrolment;
- •Haemoglobin concentration ≥ 90 g/L; white blood cell (WBC) count ≥ 3 x 109/L; platelets ≥ 75 x 109/L measured within 2 weeks of enrolment.
- •Serum creatinine ≤ 150 µmol/L, and a calculated (Cockcroft-Gault) or estimated glomerular filtration rate (GFR) of ≥ 50 mL/min measured within 2 weeks of enrolment.
- •Eastern Cooperative Oncology Group (ECOG) Performance Scale Score ≤ 2 measured within 2 weeks of enrolment;
- •Able and willing to follow instructions and comply with the protocol;
- •Ability to provide written informed consent prior to participation in the study.
排除标准
- •Systemic therapy for tumors within 2 weeks;
- •Prior external beam radiation therapy to the only evaluable lesion
- •Existing tracheostomy
- •Pregnant or breast feeding
- •Previously negative 18F-FAZA uptake of only evaluable lesion(s) within 3 months of enrolment.
- •Inability to lie still for the entire imaging time (e.g. cough, severe arthritis, etc.)
- •Inability to complete the needed investigational examinations due to other reasons (severe claustrophobia, radiation phobia, etc.)
- •Any additional medical condition, serious inter-current illness or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study performance or interpretation .
研究组 & 干预措施
[131]I-IAZA whole body and SPECT imaging
Injection of a single dose of 185MBq ( range 150-220MBq) of [131]I-IAZA prior to whole body imaging acquisition at 0-1 hrs,1-3 hrs , 4-8 hrs,19-36 hrs,41-72 hrs and 6-8 days post-injection. SPECT CT of target lesion(s) will be acquired at 19-36 hrs post injection.
干预措施: [131]I-IAZA (Drug)
结局指标
主要结局
Change in hematology/SMA-12 serum biochemistry after [131]I-IAZA injection (first 10 patients)
时间窗: Up to 36 hours post-injection
Hematology and SMA-12 serum biochemistry will be performed before injection of \[131\]I-IAZA and after the fourth scan.
Number of participants with adverse events.
时间窗: Up to 8 days after [131]I-IAZA injection
All participants will be evaluated for AE occurrence once \[131\]I-IAZA has been injected and for the following 8 days during which \[131\]I-IAZA scans will be acquired
Change in vital signs after [131]I-IAZA injection (first 10 patients)
时间窗: Up to 36 hours post-injection
Vital signs are measured before injection of \[131\]I-IAZA and after the third and fourth scans
Change in TSH level after [131]I-IAZA injection
时间窗: Before [131]I-IAZA injection and 6 weeks ± 1 week after [131]I-IAZA injection
TSH blood test will be performed before injection of \[131\]I-IAZA and 5-7 weeks after \[131\]I-IAZA injection.
次要结局
- Radioactivity of blood samples withdrawn at each imaging time point.(Up to 8 days)
- Estimating the whole body dosimetry of [131]IAZA in selected participants(Up to 8 days)
- Time to maximum [131]I-IAZA uptake(Up to 8 days)
- Biodistribution and tumor hypoxia avidity of [131]I-IAZA(Up to 8 days)
- Dose of [131]I-IAZA taken up by the tumor (in mSv/MBq) at each imaging time point in patients with positive uptake.(Up to 8 days)
- Dose (in mSv/MBq of [131]I-IAZA) to bone marrow(Up to 8 days)
- Clearance characteristics of [131]IAZA(Up to 8 days)