Clinical trial NCT01275651: Biomarkers in Bone Marrow and Blood Samples From Patients With Prostate Cancer Treated With Ketoconazole
Official title: Androgen Receptor (AR) Activity in Castration-Resistant Prostate Cancer (CRPC) and Response to Ketoconazole
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
recurrent prostate cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-01-12
Enrollment: 0
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with prostate cancer registered to Cancer and Leukemia Group B (CALGB) 9583 and CALGB 9663

Brief summary: This research trial studies biomarkers in bone marrow and blood samples from patients with prostate cancer treated with ketoconazole. Studying samples of bone marrow and blood from patients with prostate cancer in the laboratory may help doctors learn more about changes that occur in deoxyribonucleic acid (DNA) and identify biomarkers related to cancer.

Detailed description: 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.

Eligibility criteria: Inclusioin Criteria:

* Patients must have been registered to CALGB 9583 and CALGB 9663
* Adequate tissue specimen available for analysis

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Baseline
Secondary outcomes:
measure: Equal to or greater than 30% decline in PSA
timeFrame: Baseline
measure: Overall survival
timeFrame: Baseline
Other outcomes:
Locations:
city: Boston
country: United States
facility: Alliance for Clinical Trials in Oncology
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Mary-Ellen Taplin, MD
role: STUDY_CHAIR
References: