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

NCT ID: NCT01275651

Last Updated: 2019-01-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Study Classification

OBSERVATIONAL

Study Start Date

2010-12-31

Study Completion Date

2015-08-31

Brief Summary

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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

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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.

Conditions

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Prostate Cancer

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

RETROSPECTIVE

Study Groups

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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.

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

Inclusioin Criteria:

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

MALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mary-Ellen Taplin, MD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

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Alliance for Clinical Trials in Oncology

Boston, Massachusetts, United States

Site Status

Countries

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United States

Other Identifiers

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CDR0000688286

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2011-02835

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-151004

Identifier Type: -

Identifier Source: org_study_id

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