Clinical Study of Microdosing Carboplatin in Lung or Bladder Cancer
Status:
Terminated
Trial end date:
2016-11-01
Target enrollment:
Participant gender:
Summary
Carboplatin kills cancer cells mainly through induction of DNA damage (drug-DNA adducts). The
goal of this clinical trial is to determine if chemoresistance to carboplatin can be
identified by measuring carboplatin-induced DNA monoadducts, the precursor of Pt-DNA
diadducts or crosslinks, from subtherapeutic drug doses given prior to the initiation of
chemotherapy. We hypothesize that low levels of carboplatin-DNA monoadducts and rapid
drug-DNA adduct repair correlate with chemoresistance. A highly sensitive technology, called
accelerator mass spectrometry (AMS), will be used to measure carboplatin-DNA monoadducts from
patient samples. AMS can measure C-14 at the attomole level in specimens of milligram size.
In this study, patients will receive one non-toxic "microdose" (defined as 1/100th the
therapeutic dose) of C-14-labeled carboplatin. Blood specimens will be drawn for
determination of carboplatin-DNA monoadduct formation and repair in peripheral blood
mononuclear cells (PBMC), and pharmacokinetics (PK) will be determined from serum
ultrafiltrate. In patients microdosed prior to providing tumor samples, a few milligrams of
leftover tumor biopsy/resection specimens will be analyzed for formation of carboplatin-DNA
monoadducts. Patients will subsequently receive carboplatin-based chemotherapy. The levels of
microdose-induced carboplatin-DNA monoadducts will be correlated with response to
chemotherapy. Some blood and biopsy samples will be assayed by RT-PCR for several putative
resistance markers at the mRNA level. Side effects will also be monitored and compared to the
AMS data. This trial will also utilize PK, DNA repair and pharmacogenomics data in order to
determine some of the underlying chemoresistance mechanisms.
Phase:
Early Phase 1
Details
Lead Sponsor:
University of California, Davis
Collaborators:
Lawrence Livermore National Laboratory National Institutes of Health (NIH)