SBIR-STTR Award

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.

NIH Spending Category:
Cancer; Clinical Research; Genetics

Project Terms:
accelerator mass spectrometry; Adverse effects; base; Benchmarking; Biological Assay; Biological Markers; Biopsy; Cancer Patient; Carboplatin; Chemicals; Chest; Cisplatin; Clinical Data; complement C4c; Data; design; Diagnostic; Diagnostic Trial; DNA; DNA Adducts; DNA Damage; 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; pre-clinical; Procedures; Protocols documentation; radiochemical; Recurrence; response; Reverse Transcriptase Polymerase Chain Reaction; Severities; Small Business Innovation Research Grant; Technology; Therapeutic; Tissues; tumor; Tumor Tissue

We developed a technology called PlatinDx that, based upon preclinical data, can potentially identify chemoresistance in lung and bladder cancer patients before they receive carboplatin therapy. PlatinDx utilizes tracing of subtherapeutic microdoses of14C-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, progression free survival and toxicity. The goal of the project is to test the clinical feasibility of PlatinDx in bladder and lung cancer patients. The PlatinDx data will be compared to ERCC1 expression using the Response Genetics RT-PCR assay as a benchmark. The resulting feasibility data will allow the design of a Pivotal Trial, which is required for FDA clearance and product launch.