Urothelial CarcinomaNCT03998371
Application of UCAD for Diagnosing Urothelial Carcinoma.
An observational study of Urothelial Carcinoma and Diagnoses Disease, run by Changhai Hospital at 1 site in China.
Trial summary
Chromosomal instability (CIN) refers to ongoing chromosome segregation errors throughout consecutive cell divisions. CIN is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma, Diagnoses Disease, Chromosomal Abnormality
- What is being tested?
- Low-coverage whole-genome sequencing of urine exfoliated cells
- How many people
- 300 participants
- Where
- 1 siteChina
- Study dates
- 5 May 2019to 5 May 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 18 years and older
- All sexes
- Adult, Older adult
Study population: Patients diagnosed with urothelial carcinoma or participants in control group in Changhai Hospital from May 2019 till the end of this study.
Who may be able to join
- Patients diagnosed with urothelial carcinoma and planned to undergo surgery.
- Participants without any tumor disease and willing to attend the study by providing morning urine.
- Male or female patients aged >= 18 years.
- Participants signed informed consent form.
Who cannot join
- Age under 18 years
- Individuals unwilling to sign the consent form or unwilling to provide morning urine for test or unwilling to provide the medical record.
- Individuals unwilling to participate in this trial.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Changhai Hospital
Shanghai, Shanghai Municipality, 200433
Shuxiong Zeng, M.D. Ph.D, +8618930568759, zengshuxiong@126.com
About this study
Official title: Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) in Urine Exfoliated Cells for Diagnosis of Urothelial Carcinoma in in Urine Exfoliated Cells
Chromosomal instability (CIN) refers to ongoing chromosome segregation errors throughout consecutive cell divisions. CIN is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. Analyzing CIN of the DNA extracted from urothelial cells in urine samples seems a promising method for diagnosing, monitoring, and predicting the prognosis of bladder cancer patients. CIN can be assessed using experimental techniques such as bulk DNA sequencing, fluorescence in situ hybridization (FISH), or conventional karyotyping. However, these techniques are either time-consuming or non-specific. We here intend to study whether a new method named Ultrasensitive Chromosomal Aneuploidy Detection (UCAD), which is based on low-coverage whole-genome sequencing, can be used to analyze CIN thus help diagnosing and treating bladder cancer patients.
Read the detailed description
CIN results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. It will generate genomic heterogeneity that acts as a substrate for natural selection. Furthermore, it is proved that tumors with aneuploidies and polyploidy resulting from whole-genome doubling are related with metastasis, treatment resistance, and decreased overall survival. It is estimated that 60%-80% of human tumors exhibit chromosomal abnormalities suggestive of CIN. CIN positively correlates with tumor stage and is enriched in relapsed as well as metastatic tumor specimens. Due to the ubiquity of CIN in cancer cells, it is a potentially non-invasive way to detect CIN in the urothelial cells from the urine sample for diagnosing and monitoring bladder cancer patients. UCAD is a new method to detecting CIN in the DNA sample from patients, including extracting DNA from urine, analyzing DNA by low-coverage whole-genome sequencing, processing the data by bio-information techniques, and finally optimizing the management of bladder cancer patients.
The investigators intended to conduct a prospective study by analyzing urine samples from bladder cancer patients and control groups that without any tumor in the urinary system or other organs to compare the specificity and sensitivity of UCAD test for diagnosing urothelial carcinoma to other modalities, such as urine cytology or fluorescence in situ hybridization (FISH).
- Being tested
- Low-coverage whole-genome sequencing of urine exfoliated cells
- Keywords
- Urothelial Carcinoma, diagnosis, Chromosomal Aneuploidy Detection, marker, urine
- Medical subject headings
- Carcinoma, Transitional Cell, Chromosome Aberrations, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-coverage whole-genome sequencing of urine exfoliated cellsDiagnostic test
The level of CIN The extracted DNA from morning urine will be analyzed by UCAD to determine the level of CIN.
| Study group | Role | What they receive |
|---|---|---|
| Urothelial carcinoma group | Pre-surgery patients with urothelial carcinoma will be the experimental group to determine the sensitivity and specificity of UCAD analysis, the result will be compared with cytology and FISH. Receives: Diagnostic Test: Low-coverage whole-genome sequencing of urine exfoliated cells | |
| Non-cancer participants group | Patients being treated for other diseases but without any tumor will provide a negative control to provide data for determining the sensitivity and specificity of UCAD analysis. Receives: Diagnostic Test: Low-coverage whole-genome sequencing of urine exfoliated cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity of urinalysis by UCAD analysis
Number of patients "declared positive" with the UCAD test among the patients suffered from urothelial carcinoma.
Measured: Up to 1 years
Specificity of urinalysis by UCAD analysis
Number of patients "declared negative" with the UCAD test among the patients without cancer.
Measured: Through study completion, an average of 12 months
Secondary outcomes (2)
Comparison of the sensitivity of the UCAD analysis versus urine cytology
Number of patients "declared positive" with the UCAD analysis versus patients "declared positive" with the urine cytology.
Measured: Up to 1 years
Comparison of the specificity of the UCAD analysis versus urine cytology
Number of patients "declared negative" with the UCAD analysis versus patients " declared negative " with the urine cytology.
Measured: Up to 1 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2019
- Study start5 May 2019
- Primary completion5 May 2020 (estimated)
- Study completion5 May 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by Changhai HospitalThe sponsor's other registered studies.
- 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-control
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changhai Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shuxiong Zeng, Changhai Hospital
- Investigators
- Chuangliang Xu, M.D., Ph.D, Study chair, Changhai Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03998371
- Sponsor's protocol ID
- CH-urology-bladder marker-002
- Status last verified
- Jun 2019
- First submitted
- 19 Jun 2019
- Last updated
- 26 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We will try to protect the information of the included participants
Publications
Wadhwa N, Mathew BB, Jatawa SK, Tiwari A. Genetic instability in urinary bladder cancer: An evolving hallmark. J Postgrad Med. 2013 Oct-Dec;59(4):284-8. doi: 10.4103/0022-3859.123156.
PubMed 24346386Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, Shah P, Sriram RK, Watkins TBK, Taunk NK, Duran M, Pauli C, Shaw C, Chadalavada K, Rajasekhar VK, Genovese G, Venkatesan S, Birkbak NJ, McGranahan N, Lundquist M, LaPlant Q, Healey JH, Elemento O, Chung CH, Lee NY, Imielenski M, Nanjangud G, Pe'er D, Cleveland DW, Powell SN, Lammerding J, Swanton C, Cantley LC. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature. 2018 Jan 25;553(7689):467-472. doi: 10.1038/nature25432. Epub 2018 Jan 17.
PubMed 29342134Liu H, He W, Wang B, Xu K, Han J, Zheng J, Ren J, Shao L, Bo S, Lu S, Lin T, Huang J. MALBAC-based chromosomal imbalance analysis: a novel technique enabling effective non-invasive diagnosis and monitoring of bladder cancer. BMC Cancer. 2018 Jun 15;18(1):659. doi: 10.1186/s12885-018-4571-7.
PubMed 29907142Hieronymus H, Murali R, Tin A, Yadav K, Abida W, Moller H, Berney D, Scher H, Carver B, Scardino P, Schultz N, Taylor B, Vickers A, Cuzick J, Sawyers CL. Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death. Elife. 2018 Sep 4;7:e37294. doi: 10.7554/eLife.37294.
PubMed 30178746Zeng S, Ying Y, Xing N, Wang B, Qian Z, Zhou Z, Zhang Z, Xu W, Wang H, Dai L, Gao L, Zhou T, Ji J, Xu C. Noninvasive Detection of Urothelial Carcinoma by Cost-effective Low-coverage Whole-genome Sequencing from Urine-Exfoliated Cell DNA. Clin Cancer Res. 2020 Nov 1;26(21):5646-5654. doi: 10.1158/1078-0432.CCR-20-0401. Epub 2020 Oct 9.
PubMed 33037018
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) in Urine Exfoliated Cells for Diagnosis of Urothelial Carcinoma in in Urine Exfoliated Cells
- ClinicalTrials.gov ID
- NCT03998371
- Acronym / sponsor ID
- CH-urology-bladder marker-002
- Keywords
- Urothelial Carcinoma, diagnosis, Chromosomal Aneuploidy Detection, marker, urine
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Changhai HospitalUniversity, hospital or other
- Study start
- 5 May 2019 (actual)
- Primary completion
- 5 May 2020 (estimated)
- Study completion
- 5 May 2020 (estimated)
- First posted
- 26 Jun 2019 (actual)
- 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.
Chromosomal instability (CIN) refers to ongoing chromosome segregation errors throughout consecutive cell divisions. CIN is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. Analyzing CIN of the DNA extracted from urothelial cells in urine samples seems a promising method for diagnosing, monitoring, and predicting the prognosis of bladder cancer patients. CIN can be assessed using experimental techniques such as bulk DNA sequencing, fluorescence in situ hybridization (FISH), or conventional karyotyping. However, these techniques are either time-consuming or non-specific. We here intend to study whether a new method named Ultrasensitive Chromosomal Aneuploidy Detection (UCAD), which is based on low-coverage whole-genome sequencing, can be used to analyze CIN thus help diagnosing and treating bladder cancer patients.
Detailed description
CIN results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. It will generate genomic heterogeneity that acts as a substrate for natural selection. Furthermore, it is proved that tumors with aneuploidies and polyploidy resulting from whole-genome doubling are related with metastasis, treatment resistance, and decreased overall survival. It is estimated that 60%-80% of human tumors exhibit chromosomal abnormalities suggestive of CIN. CIN positively correlates with tumor stage and is enriched in relapsed as well as metastatic tumor specimens. Due to the ubiquity of CIN in cancer cells, it is a potentially non-invasive way to detect CIN in the urothelial cells from the urine sample for diagnosing and monitoring bladder cancer patients. UCAD is a new method to detecting CIN in the DNA sample from patients, including extracting DNA from urine, analyzing DNA by low-coverage whole-genome sequencing, processing the data by bio-information techniques, and finally optimizing the management of bladder cancer patients.
The investigators intended to conduct a prospective study by analyzing urine samples from bladder cancer patients and control groups that without any tumor in the urinary system or other organs to compare the specificity and sensitivity of UCAD test for diagnosing urothelial carcinoma to other modalities, such as urine cytology or fluorescence in situ hybridization (FISH).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Urothelial carcinoma group | – | Diagnostic Test: Low-coverage whole-genome sequencing of urine exfoliated cellsPre-surgery patients with urothelial carcinoma will be the experimental group to determine the sensitivity and specificity of UCAD analysis, the result will be compared with cytology and FISH. |
| Non-cancer participants group | – | Diagnostic Test: Low-coverage whole-genome sequencing of urine exfoliated cellsPatients being treated for other diseases but without any tumor will provide a negative control to provide data for determining the sensitivity and specificity of UCAD analysis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients diagnosed with urothelial carcinoma or participants in control group in Changhai Hospital from May 2019 till the end of this study.
Key inclusion criteria (4 listed)
- Patients diagnosed with urothelial carcinoma and planned to undergo surgery.
- Participants without any tumor disease and willing to attend the study by providing morning urine.
- Male or female patients aged >= 18 years.
- Participants signed informed consent form.
Key exclusion criteria (3 listed)
- Age under 18 years
- Individuals unwilling to sign the consent form or unwilling to provide morning urine for test or unwilling to provide the medical record.
- Individuals unwilling to participate in this trial.
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 |
|---|---|---|
| Low-coverage whole-genome sequencing of urine exfoliated cellsThe level of CIN The extracted DNA from morning urine will be analyzed by UCAD to determine the level of CIN. | Diagnostic test | Non-cancer participants group, Urothelial carcinoma group |
Primary outcome
Sensitivity of urinalysis by UCAD analysis
Time frame: Up to 1 years
Number of patients "declared positive" with the UCAD test among the patients suffered from urothelial carcinoma.
Specificity of urinalysis by UCAD analysis
Time frame: Through study completion, an average of 12 months
Number of patients "declared negative" with the UCAD test among the patients without cancer.
2 secondary outcomes
Comparison of the sensitivity of the UCAD analysis versus urine cytology
Time frame: Up to 1 years
Comparison of the specificity of the UCAD analysis versus urine cytology
Time frame: Up to 1 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2019.
- Background: PubMed 24346386Wadhwa N, Mathew BB, Jatawa SK, Tiwari A. Genetic instability in urinary bladder cancer: An evolving hallmark. J Postgrad Med. 2013 Oct-Dec;59(4):284-8. doi: 10.4103/0022-3859.123156.
- Background: PubMed 29342134Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, Shah P, Sriram RK, Watkins TBK, Taunk NK, Duran M, Pauli C, Shaw C, Chadalavada K, Rajasekhar VK, Genovese G, Venkatesan S, Birkbak NJ, McGranahan N, Lundquist M, LaPlant Q, Healey JH, Elemento O, Chung CH, Lee NY, Imielenski M, Nanjangud G, Pe'er D, Cleveland DW, Powell SN, Lammerding J, Swanton C, Cantley LC. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature. 2018 Jan 25;553(7689):467-472. doi: 10.1038/nature25432. Epub 2018 Jan 17.
- Background: PubMed 29907142Liu H, He W, Wang B, Xu K, Han J, Zheng J, Ren J, Shao L, Bo S, Lu S, Lin T, Huang J. MALBAC-based chromosomal imbalance analysis: a novel technique enabling effective non-invasive diagnosis and monitoring of bladder cancer. BMC Cancer. 2018 Jun 15;18(1):659. doi: 10.1186/s12885-018-4571-7.
- Background: PubMed 30178746Hieronymus H, Murali R, Tin A, Yadav K, Abida W, Moller H, Berney D, Scher H, Carver B, Scardino P, Schultz N, Taylor B, Vickers A, Cuzick J, Sawyers CL. Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death. Elife. 2018 Sep 4;7:e37294. doi: 10.7554/eLife.37294.
- Derived from this study: PubMed 33037018Zeng S, Ying Y, Xing N, Wang B, Qian Z, Zhou Z, Zhang Z, Xu W, Wang H, Dai L, Gao L, Zhou T, Ji J, Xu C. Noninvasive Detection of Urothelial Carcinoma by Cost-effective Low-coverage Whole-genome Sequencing from Urine-Exfoliated Cell DNA. Clin Cancer Res. 2020 Nov 1;26(21):5646-5654. doi: 10.1158/1078-0432.CCR-20-0401. Epub 2020 Oct 9.
- Individual participant dataSharing planned: No. We will try to protect the information of the included participants
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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.
Chuangliang Xu, M.D., Ph.D study chair
Changhai Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Urothelial Carcinoma and Diagnoses Disease, run by Changhai Hospital at 1 site in China.
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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 26 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shuxiong zeng, M.D., Ph.D (+8618930568759, zengshuxiong@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity of urinalysis by UCAD analysis (time frame: Up to 1 years). The study lists 2 primary outcomes in all. 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 NCT03998371, which also lists 5 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 26 Jun 2019.