Biomarkers in Bone Marrow and Blood Samples From Patients With Prostate Cancer Treated With Ketoconazole

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

Inclusioin Criteria:

- Patients must have been registered to CALGB 9583 and CALGB 9663

- Adequate tissue specimen available for analysis