Phase 0 carboplatin microdosing diagnostics trial

0 期卡铂微剂量诊断试验

• 批准号: 8179262
• 负责人: Paul Thomas Henderson
• 金额: $ 19.56万
• 依托单位: ACCELERATED MEDICAL DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2011-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8179262
• 关键词: Adverse effects; Benchmarking; Biological Assay; Biological Markers; Biopsy; Cancer Patient; Carboplatin; Chemicals; Chest; Cisplatin; Clinical Data; DNA; DNA Adducts; DNA Damage; Data; Diagnostic; Diagnostic Trial; Dose; ERCC1 gene; Genetic; Goals; Hour; Label; Left; Leukocytes; Malignant neoplasm of lung; Measures; Mole the mammal; Outcome; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Phase; Procedures; Protocols documentation; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; Severities; Small Business Innovation Research Grant; Technology; Therapeutic; Tissues; Tumor Tissue; accelerator mass spectrometry; base; complement C4c; design; pre-clinical; radiochemical; response; tumor

We developed a technology called PlatinDx that, based upon preclinical data, can potentially identify chemoresistance in cancer patients before they receive carboplatin or cisplatin therapy. PlatinDx utilizes tracing of subtherapeutic "microdoses" of 14C-labeled carboplatin with accelerator mass spectrometry (AMS), which has attomole (10-18 mole) sensitivity for 14C. We hypothesize that DNA damage caused by a single subtoxic microdose of carboplatin can predict patient outcomes such as tumor shrinkage and survival . The goal of the project is to define the appropriate chemical (-1 /1 DOth the therapeutic dose) and radiochemical (few percent of a chest x-ray exposure) microdose composition, to establish protocols for the procedure and to gather preliminary clinical data. Lung cancer patients will each receive a 14C-carboplatin microdose a few hours prior to normal biopsy. DNA will be isolated from white blood cells and left over tumor biopsy tissue. Drug-DNA damage levels will be measured by AMS and compared to outcomes such as tumor shrinkage, recurrence and severity of side effects. The data will be compared to ERCC1 expression and other biomarkers using the Response Genetics RT-PCR assay as a benchmark. The resulting feasibility data will allow the design of an SBIR Phase II pivotal diagnostic study.

我们开发了一种称为Platindx的技术，该技术基于临床前数据，可以在癌症患者接受卡铂或顺铂治疗之前可能识别化学耐药性。 Platindx利用14C标记的卡泊蛋白的亚治疗“微剂量”和加速器质谱法（AMS）的追踪，该质谱（AMS）具有14C的敏感性（10-18摩尔）敏感性。我们假设由单一的无毒微剂量的卡泊素损伤可以预测患者的结局，例如肿瘤收缩和存活。该项目的目的是定义适当的化学物质（-1 /1的治疗剂量）和 放射性化学（胸部X射线暴露的百分之几）微剂组成，以建立该过程的方案并收集初步的临床数据。正常活检前几个小时，肺癌患者将分别患有14C-氨基铂微剂量。 DNA将从白细胞中分离出来，并留在肿瘤活检组织上。药物-DNA损伤水平将通过AMS测量，并将其与诸如肿瘤收缩，复发和副作用的严重程度等结果进行比较。使用响应遗传学RT-PCR分析作为基准，将数据与ERCC1表达和其他生物标志物进行比较。由此产生的可行性数据将允许设计SBIR II期关键诊断研究。