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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01275651
First Posted: January 12, 2011
Last Update Posted: August 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
  Purpose
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.

Condition Intervention
Prostate Cancer Other: laboratory biomarker analysis

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Androgen Receptor (AR) Activity in Castration-Resistant Prostate Cancer (CRPC) and Response to Ketoconazole

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Baseline ]

Secondary Outcome Measures:
  • Equal to or greater than 30% decline in PSA [ Time Frame: Baseline ]
  • Overall survival [ Time Frame: Baseline ]

Biospecimen Retention:   Samples With DNA
Tissue, bone marrow, and blood

Estimated Enrollment: 48
Study Start Date: December 2010
Estimated Primary Completion Date: January 2100 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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
Correlative studies

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

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with prostate cancer registered to Cancer and Leukemia Group B (CALGB) 9583 and CALGB 9663
Criteria

Inclusioin Criteria:

  • Patients must have been registered to CALGB 9583 and CALGB 9663
  • Adequate tissue specimen available for analysis
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01275651


Locations
United States, Massachusetts
Alliance for Clinical Trials in Oncology
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Mary-Ellen Taplin, MD Dana-Farber Cancer Institute
  More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01275651     History of Changes
Other Study ID Numbers: CALGB-151004
CDR0000688286 ( Registry Identifier: NCI Physician Data Query )
NCI-2011-02835 ( Registry Identifier: NCI Clinical Trial Reporting Program )
First Submitted: January 11, 2011
First Posted: January 12, 2011
Last Update Posted: August 8, 2017
Last Verified: August 2017

Keywords provided by Alliance for Clinical Trials in Oncology:
adenocarcinoma of the prostate
recurrent prostate cancer

Additional relevant MeSH terms:
Genital Diseases, Male
Prostatic Diseases
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Ketoconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors