Predicting Response to Platinum Chemotherapy in Metastatic Castration Resistant Prostate Ca(mCRPC)Using a Genomic Signature for "BRCAness": A Phase II Prospective Open Label Clinical Trial of Satraplatin in Men With mCRPC Who Have Progressed on Docetaxel
We will be developing a genomic based signature of "BRCAness" based on literature of
genomic signatures from women with breast cancer and germline BRCA mutations.The "BRCAness"
breast cancer signature will differentiate germline BRCA 1/2 breast cancers from standard
estrogen-receptor (+) breast cancers. We will obtain a library of genomic signatures
Recently these techniques have been used to develop a transcriptional "signature" for
androgen receptor (AR) activity in men with CRPC(Castration Resistant Prostate Cancer). The
investigator will apply the "BRCAness" breast cancer signature to pathological prostate
cancer specimens to determine the percentage of patients in the overall prostate cancer
population that express this signature, as well as the clinical and histological phenotype
of this population.
This novel prostate cancer "BRCAness" signature will be developed over a period of 4-6
months. This "BRCAness" signature has not previously been evaluated in prostate cancer
patients and would be expected, based on known characteristics of BRCA mutant breast and
ovarian cancers, to be more platinum-responsive. Relevant clinical data, including
histology, grade, stage, size of residual tumor, recurrence, and survival, will be obtained
from outpatient and inpatient charts to perform subsequent correlative studies.
All patients enrolled in the phase II clinical trial with satraplatin will have
pre-treatment biopsies of metastatic sites. All of the specimens will be frozen, batched and
stored as previously described. We anticipate that all patients will be enrolled 16 months
from when the trial opens. When the last patient is enrolled in the trial and all of the
metastatic biopsies have been collected, they will be shipped in bulk on dry ice to
laboratory for RNA(ribonucleic acid) isolation, RNA quality assessment and processing,
microarray hybridization, microarray data quality assessment, and "BRCAness" prostate cancer
signature application. Frozen biopsies will be processed for microarray analysis using laser
capture microdissection and RNA amplification using adaptations of previously published
methods. The application of the prostate cancer BRCAness signature will take place over two
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the efficacy of Satraplatin as second line therapy in men with CRCP
Patients with good tolerance of treatment who have a 30% PSA decline from their pre-treatment level withtin 3 months of treatment initiation will be considered responders provided objective tumor measurements are stable or also demonstrate response.
William K Oh, M.D.
Mount Sinai School of Medicine
United States: Food and Drug Administration
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