Utilizing A Genomic Sig for "BRCAness" to Eval the Efficacy of Satraplatin in Men With Met. Castration Resistant Prostate Ca
The purpose of the study is to test genes for BRCAness(BRCA[BReast CAncer] gene) Studying these genes could help predict which patients would benefit from treatment with satraplatin, a medication being used for subjects who have failed prior chemotherapy. All subjects will have a biopsy of metastatic lesions to measure BRCAness (a gene signature). This gene signature may be able to predict response to satraplatin and a tool will be developed to be able to screen patients likely to benefit from satraplatin. Subjects will all receive Satraplatin days 1-5 and Prednisone 5 mg twice daily every 35 days. Response rates will be evaluated every 2 cycles or approximately every 9 weeks. Patients will be considered responders if they have measurable disease meeting criteria for partial or complete response. PSA will be measured day one of each treatment cycle. Each treatment cycle is 35 days.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- To determine the efficacy of Satraplatin as second line therapy in men with CRCP [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]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.
- To assess response rates [ Time Frame: 3 months ] [ Designated as safety issue: No ]Response will be evaluated in this study using PSA (Prostate-Specific Antigen) measurements (every 4 weeks) and by using the Response Evaluation Criteria in Solid Tumors(RECIST) every 2 cycles (or approximately every 9 weeks). PSA response will be measured as the percentage of change in PSA from baseline to 12 weeks in therapy (or earlier if patients discontinue therapy prior to 12 weeks) as well as the maximum decline in PSA that occurs at any point during treatment. PSA decline will be reported globally using a waterfall plot.
- Progression Free Survival (PFS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]Progression Free Survival is measured from the time of the initiation of therapy until the first dat that recurrent or progressive disease is objectively documentsd. Progression is a composite endpoint that can be based upon PSA, objective measures of disease, symptoms or death.
- Overall Survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]Patients will be followed for a minimum of 24 months or until death. Patients and/or their family members will be contacted via telephone calls or certified letter.
|Study Start Date:||December 2010|
|Study Completion Date:||May 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
|Satraplatin, Single Arm||
Satraplatin 80mg/m2 day 1-5 every 35 days Prednisone 5 mg twice daily every 35 days
Other Name: JM-118
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 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01289067
|United States, New York|
|Mount Sinai Medical Center|
|New York, New York, United States, 10029|
|Principal Investigator:||William K Oh, M.D.||Mount Sinai School of Medicine|