Phase 0 carboplatin microdosing diagnostics trial

我们开发了一种名为PlatinDx的技术，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潜在地识别出化疗耐药性。PlatinDx利用加速器质谱法（AMS）追踪亚治疗“微剂量”的14C标记卡铂，该方法对14C具有原子（10-18摩尔）灵敏度。我们假设单次亚毒性微剂量卡铂引起的DNA损伤可以预测患者的预后，如肿瘤缩小和生存。该项目的目标是确定适当的化学制剂（治疗剂量的-1 /1）和

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.