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

Prostate Cancer Clinical Trial

Official title:

Androgen Receptor (AR) Activity in Castration-Resistant Prostate Cancer (CRPC) and Response to Ketoconazole

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01275651
• Other study ID #: CALGB-151004
• Secondary ID: CDR0000688286NCI
• Status: Withdrawn
• Start date: December 2010
• Est. completion date: August 2015

Study information

• Verified date: January 2019
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

Inclusioin Criteria:

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

• Adequate tissue specimen available for analysis

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Alliance for Clinical Trials in Oncology	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)		Baseline
Secondary	Equal to or greater than 30% decline in PSA		Baseline
Secondary	Overall survival		Baseline