Biomarkers in Bone Marrow and Blood Samples From Patients With Prostate Cancer Treated With Ketoconazole
|ClinicalTrials.gov Identifier: NCT01275651|
Recruitment Status : Active, not recruiting
First Posted : January 12, 2011
Last Update Posted : August 8, 2017
|Condition or disease||Intervention/treatment|
|Prostate Cancer||Other: laboratory biomarker analysis|
I. 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.
I. To determine if expression of androgen transport/synthesis/metabolism genes (including cytochrome P450, family 17, subfamily A, polypeptide 1 [CYP17A1], aldo-keto reductase family 1 [AKR1]C3, hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 [HSD3B2], hydroxysteroid [17-beta] dehydrogenase [HSD17B]3, HSD17B6, AKR1C2, AKR1C1, UGTB15, UGTB17, steroid-5-alpha-reductase, alpha polypeptide 1 [3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha] [SRD5A]1, SRD5A2, SRD5A3, and solute carrier organic anion transporter family, member 2B1 [SLCO2B1]) correlate with detected AR activity, time to progression (progression free survival [PFS]) following treatment with ketoconazole, and overall survival.
II. To determine if semi-quantitative immunohistochemical analysis of AR and AKR1C3 protein levels correlate with PFS following treatment with ketoconazole.
III. To determine if specific AR splice variations correlate with PFS in response to ketoconazole.
IV. To determine if detected activity of signaling pathways that interact with AR pathway activity (e.g., phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [PI3K] and downstream effectors, SRC proto-oncogene, non-receptor tyrosine kinase [SRC], others) correlate with detected AR activity, PFS, and OS.
V. To determine if AR gene amplification correlates with detected AR activity and PFS on ketoconazole.
VI. To determine if levels of testosterone and dihydrotestosterone (DHT) from tumor tissue correlate with AR activity and PFS on ketoconazole.
VII. To determine the presence of specific prostate cancer-associated gene translocations in each sample of CRPC.
VIII. To provide an unbiased data set of gene expression in CRPC that will markedly expand the currently available public domain data.
IX. To provide a library of amplified ribonucleic acid (RNA) and complementary (c)DNA for further analysis by other investigators.
Previously collected bone marrow, tissue, and blood samples are analyzed for AR activity, AR splice variations, expression of androgen transport/synthesis/metabolism genes, AKR1C3 protein levels, and testosterone and dihydrotestosterone levels via reverse transcription (RT)-polymerase chain reaction (PCR), single nucleotide polymorphisms (SNP) microarrays, immunohistochemistry (IHC), gene expression analysis, and mass spectrometry methods.
|Study Type :||Observational|
|Estimated Enrollment :||48 participants|
|Official Title:||Androgen Receptor (AR) Activity in Castration-Resistant Prostate Cancer (CRPC) and Response to Ketoconazole|
|Study Start Date :||December 2010|
|Estimated Primary Completion Date :||January 2100|
Ancillary-Correlative (AR activity in CRPC)
Previously collected bone marrow tissue and blood samples are analyzed for AR activity, AR splice variations, expression of androgen transport/synthesis/metabolism genes, AKR1C3 protein levels, and testosterone and dihydrotestosterone levels via RT-PCR, SNP microarrays, IHC, gene expression analysis, and mass spectrometry methods.
Other: laboratory biomarker analysis
- Progression-free survival (PFS) [ Time Frame: Baseline ]
- Equal to or greater than 30% decline in PSA [ Time Frame: Baseline ]
- Overall survival [ Time Frame: Baseline ]
Biospecimen Retention: Samples With DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01275651
|United States, Massachusetts|
|Alliance for Clinical Trials in Oncology|
|Boston, Massachusetts, United States, 02115|
|Study Chair:||Mary-Ellen Taplin, MD||Dana-Farber Cancer Institute|