Non-invasive Imaging of Tumor Hypoxia With [18F]HX4 Positron-Emission-Tomography (PET): A Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Quantification of tumor hypoxia with [18F] HX4 PET imaging, evaluated by the measurement of a tumor-to-background (T/B) ratio on the [18F]HX4 PET/CT
研究概览
简要总结
Regulation of tissue oxygen homeostasis is critical for cell function, proliferation and survival. Evidence for this continues to accumulate along with our understanding of the complex oxygen-sensing pathways present within cells. Several pathophysiological disorders are associated with a loss in oxygen homeostasis, including heart disease, stroke, and cancer. The microenvironment of tumors in particular is very oxygen heterogeneous, with hypoxic areas which may explain our difficulty treating cancer effectively. Prostate carcinomas are known to be hypoxic. Increasing levels of hypoxia within prostatic tissue is related to increasing clinical stage, patient age and a more aggressive prostate cancer. Several researches indicated that hypoxia might also play a role in esophageal cancer. In glial brain tumors, hypoxia is correlated with more rapid tumor recurrence and the hypoxic burden in newly diagnosed glioblastomas is linked to the biological aggressiveness. In brain metastases CA-IX expression (a marker for hypoxia) is correlated to the primary non-small cell lung carcinomas. Hypoxia enhances proliferation, angiogenesis, metastasis, chemoresistance and radioresistance of hepatocellular carcinoma. The hypoxic markers HIF-1α, VEGF, CA-IX and GLUT-1 were all over expressed in colorectal cancer and its liver metastases. Based on literature, hypoxia in tumors originating or disseminated to prostate, esophagus, brain and rectum cancer will be studied in this trial.
详细描述
Rationale: Non-invasive imaging of hypoxia with the aid of PET-scans could help to select the patients having a hypoxic tumor, who could be treated with specific anti-hypoxic treatments. The added value of additional anti-hypoxic treatments depends on the presence of hypoxia and adequate patient selection. Several 2-nitroimidazoles, labeled with Fluor-18 (18F) have already been used in patients to identify hypoxia. However, suboptimal image quality and unpredictable kinetics limit their use. In extensive pre-clinical models and clinical trials the combination of HX4 labeled with 18F showed to be a promising and non-toxic new probe to determine hypoxia. With this tracer the proportion of hypoxic tumors in several cancer types will be verified.
Objective: Determine if tumor hypoxia can be accurately visualized with [18F]HX4 in solid lesions.
Study design: Phase II, several solid tumors, single-centre, imaging, non-randomized, open label trial.
Study population:
Main patient characteristics are:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological/cytological confirmed carcinoma of de esophagus, rectum or prostate or radiological suspicion for Grade IV glioma (primary brain tumor) or brain metastases
- •WHO performance status 0 to
- •Adequate renal function (calculated creatinine clearance at least 60 ml/min).
- •The patient is willing and capable to comply with study procedures
- •18 years or older
- •Have given written informed consent before patient registration
排除标准
- •Recent (< 3 months) myocardial infarction
- •Pregnant or breast feeding and willing to take adequate contraceptive measures during the study
研究组 & 干预措施
[18F]HX4 PET imaging
Injection with the hypoxia tracer [18F]HX4 and PET imaging at baseline for esophageal, rectal, prostate cancer, primary brain tumor (grade IV glioma) and brain metastases and after 2 weeks of radiotherapy for esophageal, rectal and brain metastases
干预措施: Injection with the hypoxia tracer [18F]HX4, (Drug)
结局指标
主要结局
Quantification of tumor hypoxia with [18F] HX4 PET imaging, evaluated by the measurement of a tumor-to-background (T/B) ratio on the [18F]HX4 PET/CT
时间窗: 4 years
Quantification of tumor hypoxia with \[18F\] HX4 PET imaging
Visualization of tumor hypoxia with [18F] HX4 PET imaging, valuated by the measurement of a tumor-to-background (T/B) ratio on the [18F]HX4 PET/CT
时间窗: 4 years
Visualization of tumor hypoxia with \[18F\] HX4 PET imaging
次要结局
- Correlation of hypoxia imaging with blood hypoxia markers will be measured by the Pearson or Spearman correlation coefficient(4 years)
- Correlation of hypoxia imaging with tumor tissue biomarkers will be measured by the Pearson or Spearman correlation coefficient(4 years)
- Evaluation of tumor hypoxia changes during treatment by comparison of the PET uptake values in the tumor, measured before and during treatment(4 years)
- Spatial correlation of [18F] HX4-PET with imaging three months after treatment using a correlation coefficient(3 months)
- Time between [18F] HX4 uptake with local and locoregional tumor recurrence and survival(4 years)
- Spatial correlation of [18F] HX4-PET with imaging pre-treatment using a correlation coefficient(4 years)