Biomarkers in Bone Marrow and Blood Samples From Patients With Prostate Cancer Treated With Ketoconazole
Recruitment status was Not yet recruiting
RATIONALE: Studying samples of bone marrow and blood from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.
PURPOSE: This laboratory study is studying biomarkers in bone marrow and blood samples from patients with prostate cancer treated with ketoconazole.
Genetic: gene expression analysis
Genetic: microarray analysis
Genetic: protein analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: mass spectrometry
|Official Title:||Androgen Receptor (AR) Activity in Castration-Resistant Prostate Cancer (CRPC) and Response to Ketoconazole|
- Progression-free survival (PFS) of men treated with ketoconazole [ Designated as safety issue: No ]
- At least 30% decline in PSA from baseline [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
|Study Start Date:||December 2010|
|Estimated Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
- To determine whether pre-treatment androgen receptor (AR) activity correlates with progression-free survival (PFS) of men with castration-resistant prostate cancer (CRPC) treated with ketoconazole.
- To determine whether expression of androgen transport/synthesis/metabolism genes (including CYP17A1, AKR1C3, HSD3B2, HSD17B3, HSD17B6, AKR1C2, AKR1C1, UGTB15, UGTB17, SRD5A1, SRD5A2, SRD5A3, and SLCO2B1) correlate with detected AR activity, time to progression, and overall survival (OS) following treatment with ketoconazole.
- To determine whether semi-quantitative immunohistochemical analysis of AR and AKR1C3 protein levels correlate with PFS following treatment with ketoconazole.
- To determine whether specific AR splice variations correlate with PFS in response to ketoconazole.
- To determine whether detected activity of signaling pathways that interact with AR pathway activity (e.g., PI3K and downstream effectors, SRC, others) correlate with detected AR activity, PFS, and OS.
- To determine whether AR gene amplification correlates with detected AR activity and PFS on ketoconazole.
- To determine whether levels of testosterone and dihydrotestosterone from tumor tissue correlate with AR activity and PFS on ketoconazole.
- To determine the presence of specific prostate cancer-associated gene translocations in each sample of CRPC.
- To provide an unbiased data set of gene expression in CRPC that will markedly expand the currently available public domain data.
- To provide a library of amplified RNA and cDNA for further analysis by other investigators.
OUTLINE: This is a multicenter study.
Archived bone marrow tissue and blood samples are analyzed for androgen receptor (AR), AR splice variations, expression of androgen transport/synthesis/metabolism genes, AKR1C3 protein levels, and testosterone and dihydrotestosterone levels by RT-PCR, SNP microarrays, IHC, gene expression analysis, and mass spectrometry methods.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01275651
|Principal Investigator:||Mary-Ellen Taplin, MD||Dana-Farber Cancer Institute|