Prostatic NeoplasmsNCT02771769
Analysis of Cell-free DNA (cfDNA) in Men With Elevated PSA Levels
An observational study of Prostatic Neoplasms, run by Chronix Biomedical Corporation at 2 sites in United States.
Trial summary
This is a multi-centre prospective study in which blood samples will be taken from 1500 male patients aged between 21-80 scheduled for prostate biopsy. Analysis of cell-free cancer DNA extracted from these samples will be undertaken to determine whether copy number instability scores derived from the cfDNA correlates… Read more about this study
- Who is it for?
- Ages 21 to 80 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- blood draw
- How many people
- 500 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2016to 1 Jan 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Male subjects between the ages of 21-80 who are scheduled for a prostate biopsy and meet one of the eligibility criteria listed below.
Who may be able to join
- Who, in the opinion of the site Investigator, have an abnormal PSA level as measured by a CLIA certified laboratory or non-USA equivalent within the last 60 days, and/or
- Who, in the opinion of the site Investigator, have an abnormal digital rectal examination
Who cannot join
- Male subjects with active or historical histologically confirmed diagnosis of malignancy
- Male subjects who have participated in a clinical trial involving an investigational drug within the 28 days prior to signing the informed consent form
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Maryland Cancer Center
Baltimore, Maryland, 21201
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
About this study
Official title: A Multi-center Prospective Study to Analyze Cancer-derived Cell-free DNA (cfDNA) in Men With Elevated PSA Levels
This is a multi-centre prospective study in which blood samples will be taken from 1500 male patients aged between 21-80 scheduled for prostate biopsy. Analysis of cell-free cancer DNA extracted from these samples will be undertaken to determine whether copy number instability scores derived from the cfDNA correlates with PSA screening levels and prostate biopsy results (i.e. Gleason score) in these patients.
Read the detailed description
The prostate is the most common site of cancer in men with 240,000 new cases diagnosed annually in the United States with approximately 28,000 yearly deaths. Prostate screening typically relies on digital rectal exam (DRE) and prostate specific antigen (PSA) levels. Limitations of the PSA test include its low sensitivity and low specificity and its inability to distinguish between low-grade and high-grade lesions. Recent screening trials suggest that PSA-based screening programs result in small or no reduction in mortality, and have significant treatment-related adverse events (AEs). Better serum/plasma biomarkers are needed to supplement the PSA test in the diagnosis and management of a disease with a multiplicity of presentations and clinical outcomes.
Cancer-derived DNA present in peripheral blood (referred to as cell-free DNA or cfDNA) was first reported in 1948, but research into this area remained in a dormant state for over 50 years. Over the last ten years however, the development of Next Generation Sequencing (NGS) using massive parallel arrays has allowed researchers to create a database robust enough to distinguish normal genomic from non-diploid cfDNA. In 2008, fetal trisomy of chromosome 21 was detected by analyzing cfDNA in maternal blood. Since then, the method has been validated for trisomy 13, 18, and 21 as a clinical laboratory procedure with remarkable accuracy >99%. Recently, cancer derived cfDNA has been demonstrated to recapitulate genomic tumor DNA. Current clinical acceptance of the utility of cfDNA in cancer diagnosis has been demonstrated in multiple abstracts at the 2014 and 2015 ASCO meetings in Chicago.
In a recent publication in Clinical Chemistry, researchers at Vanderbilt University, Gottingen, Germany, and at the University of Toronto, Canada, analyzed cfDNA in the bloodstream from healthy controls as compared to those with clinically diagnosed prostate cancer. The results of this study demonstrated that it is possible to distinguish prostate cancer from healthy controls without prior knowledge of the genetic signature of the tumors and with over three times the sensitivity of the FDA-approved blood test for prostate cancer (i.e., prostate-specific antigen (PSA)). The study examined serum from more than 200 subjects with prostate cancer and more than 200 controls. The comparative data included PSA levels and prostate tissue biopsy grading (referred to as the Gleason score). The technique distinguished prostate cancer from normal controls with 84% accuracy and cancer from benign hyperplasia and prostatitis with an accuracy of 91%. Because the method quantifies the inherent chromosomal instability of cancer and can be followed as a function of time (without having to do an invasive tissue biopsy), it is called a "liquid biopsy." This multi-centre clinical study will analyze cfDNA from subjects scheduled for prostate biopsy and is designed to validate the results obtained in the above-mentioned retrospective study. If validated, the prostate cfDNA determination test will provide a non-invasive test to aid in the diagnosis of prostate cancer, as well as provide guidance on whether a biopsy should be performed.
With regard to the study procedures used, the study subject will undergo routine venipuncture and ~20 millilitres of blood (approximately 2 tablespoons) will be collected. The blood will then be processed by the Sponsor's laboratory and sent to the Sponsor's testing facility in Gottingen, Germany.
- Conditions
- Prostatic Neoplasms
- Being tested
- blood draw
- Keywords
- cell-free DNA, copy number instability, liquid biopsy, cancer
- Medical subject headings
- Prostatic Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood drawOther
Participants will have a venous blood draw of ~20mLs before prostate biopsy. The biopsy will then be performed and histologically graded for any malignancy present. This grade will be statistically analyzed with respect to the Copy Number Instability (CNI) determined from the results of the molecular examination of the cell-free DNA in the blood.
What is being measured
The primary outcome is the main question the study is designed to answer.
CNI correlation with biopsy
To determine if copy number instability (CNI scores) derived from analysis of cell-free cancer DNA (cfDNA) in patients undergoing prostate biopsy correlates with biopsy diagnosis of prostate cancer.
Measured: Through completion of study and all data analysis which may take up to 2 years.
Secondary outcomes (2)
CNI correlation with BPH
To determine if copy number instability (CNI scores) derived from analysis of cell-free DNA (cfDNA) in patients undergoing prostate biopsy can distinguish between biopsy diagnosis of benign prostatic hyperplasia (BPH) and prostate cancer.
Measured: Through completion of study and all data analysis which may take up to 2 years.
CNI correlation with PIN
To determine if copy number instability (CNI scores) derived from analysis of cell-free DNA (cfDNA) in patients undergoing prostate biopsy correlates with measured evidence of prostatic intraepithelial neoplasia (PIN).
Measured: Through completion of study and all data analysis which may take up to 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2016 (estimated)
- Study startJan 2016
- Primary completion1 Jan 2020
- Study completion1 Jan 2020
Why it stopped: Data review
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chronix Biomedical Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Smerud Medical Research International AS, Vanderbilt University
- Responsible party
- Sponsor
- Investigators
- David F Penson, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02771769
- Sponsor's protocol ID
- CHX-2015-01
- Status last verified
- Jan 2020
- First submitted
- 10 May 2016
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Participants may request data upon writing to their physician. Data will not be available until after publication of data.
Publications
Chou R, Croswell JM, Dana T, Bougatsos C, Blazina I, Fu R, Gleitsmann K, Koenig HC, Lam C, Maltz A, Rugge JB, Lin K. Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2011 Dec 6;155(11):762-71. doi: 10.7326/0003-4819-155-11-201112060-00375. Epub 2011 Oct 7.
PubMed 21984740Bill-Axelson A, Holmberg L, Garmo H, Rider JR, Taari K, Busch C, Nordling S, Haggman M, Andersson SO, Spangberg A, Andren O, Palmgren J, Steineck G, Adami HO, Johansson JE. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014 Mar 6;370(10):932-42. doi: 10.1056/NEJMoa1311593.
PubMed 24597866Renard E, Bringer J, Augustin I, Orsetti A, Jaffiol C. [Value of dexamethasone suppression tests in the diagnosis of hypercortisolism of ectopic or adrenal origin]. Presse Med. 1989 Feb 25;18(8):435. No abstract available. French.
PubMed 2540489
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center Prospective Study to Analyze Cancer-derived Cell-free DNA (cfDNA) in Men With Elevated PSA Levels
- ClinicalTrials.gov ID
- NCT02771769
- Acronym / sponsor ID
- CHX-2015-01
- Conditions
- Prostatic Neoplasms
- Keywords
- cell-free DNA, copy number instability, liquid biopsy, cancer
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Data review
- Enrolment
- 500 participants (actual)
- Lead sponsor
- Chronix Biomedical CorporationIndustry (pharma, biotech, devices)
- Collaborators
- Smerud Medical Research International AS, Vanderbilt University
- Study start
- Jan 2016
- Primary completion
- 1 Jan 2020 (actual)
- Study completion
- 1 Jan 2020 (actual)
- First posted
- 13 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-centre prospective study in which blood samples will be taken from 1500 male patients aged between 21-80 scheduled for prostate biopsy. Analysis of cell-free cancer DNA extracted from these samples will be undertaken to determine whether copy number instability scores derived from the cfDNA correlates with PSA screening levels and prostate biopsy results (i.e. Gleason score) in these patients.
Detailed description
The prostate is the most common site of cancer in men with 240,000 new cases diagnosed annually in the United States with approximately 28,000 yearly deaths. Prostate screening typically relies on digital rectal exam (DRE) and prostate specific antigen (PSA) levels. Limitations of the PSA test include its low sensitivity and low specificity and its inability to distinguish between low-grade and high-grade lesions. Recent screening trials suggest that PSA-based screening programs result in small or no reduction in mortality, and have significant treatment-related adverse events (AEs). Better serum/plasma biomarkers are needed to supplement the PSA test in the diagnosis and management of a disease with a multiplicity of presentations and clinical outcomes.
Cancer-derived DNA present in peripheral blood (referred to as cell-free DNA or cfDNA) was first reported in 1948, but research into this area remained in a dormant state for over 50 years. Over the last ten years however, the development of Next Generation Sequencing (NGS) using massive parallel arrays has allowed researchers to create a database robust enough to distinguish normal genomic from non-diploid cfDNA. In 2008, fetal trisomy of chromosome 21 was detected by analyzing cfDNA in maternal blood. Since then, the method has been validated for trisomy 13, 18, and 21 as a clinical laboratory procedure with remarkable accuracy >99%. Recently, cancer derived cfDNA has been demonstrated to recapitulate genomic tumor DNA. Current clinical acceptance of the utility of cfDNA in cancer diagnosis has been demonstrated in multiple abstracts at the 2014 and 2015 ASCO meetings in Chicago.
In a recent publication in Clinical Chemistry, researchers at Vanderbilt University, Gottingen, Germany, and at the University of Toronto, Canada, analyzed cfDNA in the bloodstream from healthy controls as compared to those with clinically diagnosed prostate cancer. The results of this study demonstrated that it is possible to distinguish prostate cancer from healthy controls without prior knowledge of the genetic signature of the tumors and with over three times the sensitivity of the FDA-approved blood test for prostate cancer (i.e., prostate-specific antigen (PSA)). The study examined serum from more than 200 subjects with prostate cancer and more than 200 controls. The comparative data included PSA levels and prostate tissue biopsy grading (referred to as the Gleason score). The technique distinguished prostate cancer from normal controls with 84% accuracy and cancer from benign hyperplasia and prostatitis with an accuracy of 91%. Because the method quantifies the inherent chromosomal instability of cancer and can be followed as a function of time (without having to do an invasive tissue biopsy), it is called a "liquid biopsy." This multi-centre clinical study will analyze cfDNA from subjects scheduled for prostate biopsy and is designed to validate the results obtained in the above-mentioned retrospective study. If validated, the prostate cfDNA determination test will provide a non-invasive test to aid in the diagnosis of prostate cancer, as well as provide guidance on whether a biopsy should be performed.
With regard to the study procedures used, the study subject will undergo routine venipuncture and ~20 millilitres of blood (approximately 2 tablespoons) will be collected. The blood will then be processed by the Sponsor's laboratory and sent to the Sponsor's testing facility in Gottingen, Germany.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 21 to 80 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Male subjects between the ages of 21-80 who are scheduled for a prostate biopsy and meet one of the eligibility criteria listed below.
Key inclusion criteria (2 listed)
- Who, in the opinion of the site Investigator, have an abnormal PSA level as measured by a CLIA certified laboratory or non-USA equivalent within the last 60 days, and/or
- Who, in the opinion of the site Investigator, have an abnormal digital rectal examination
Key exclusion criteria (2 listed)
- Male subjects with active or historical histologically confirmed diagnosis of malignancy
- Male subjects who have participated in a clinical trial involving an investigational drug within the 28 days prior to signing the informed consent form
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood drawParticipants will have a venous blood draw of ~20mLs before prostate biopsy. The biopsy will then be performed and histologically graded for any malignancy present. This grade will be statistically analyzed with respect to the Copy Number Instability (CNI) determined from the results of the molecular examination of the cell-free DNA in the blood. | Other | – |
Primary outcome
CNI correlation with biopsy
Time frame: Through completion of study and all data analysis which may take up to 2 years.
To determine if copy number instability (CNI scores) derived from analysis of cell-free cancer DNA (cfDNA) in patients undergoing prostate biopsy correlates with biopsy diagnosis of prostate cancer.
2 secondary outcomes
CNI correlation with BPH
Time frame: Through completion of study and all data analysis which may take up to 2 years.
CNI correlation with PIN
Time frame: Through completion of study and all data analysis which may take up to 2 years.
Results and safety
The study was stopped early (reason given: Data review). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Results publication: PubMed 21984740Chou R, Croswell JM, Dana T, Bougatsos C, Blazina I, Fu R, Gleitsmann K, Koenig HC, Lam C, Maltz A, Rugge JB, Lin K. Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2011 Dec 6;155(11):762-71. doi: 10.7326/0003-4819-155-11-201112060-00375. Epub 2011 Oct 7.
- Results publication: PubMed 24597866Bill-Axelson A, Holmberg L, Garmo H, Rider JR, Taari K, Busch C, Nordling S, Haggman M, Andersson SO, Spangberg A, Andren O, Palmgren J, Steineck G, Adami HO, Johansson JE. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014 Mar 6;370(10):932-42. doi: 10.1056/NEJMoa1311593.
- Results publication: PubMed 2540489Renard E, Bringer J, Augustin I, Orsetti A, Jaffiol C. [Value of dexamethasone suppression tests in the diagnosis of hypercortisolism of ectopic or adrenal origin]. Presse Med. 1989 Feb 25;18(8):435. No abstract available. French.
- Individual participant dataSharing planned: Yes. Participants may request data upon writing to their physician. Data will not be available until after publication of data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David F Penson, MD principal investigator
Vanderbilt University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prostatic Neoplasms, run by Chronix Biomedical Corporation at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Data review). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CNI correlation with biopsy (time frame: Through completion of study and all data analysis which may take up to 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02771769, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.