Urothelial CarcinomaNCT04432909
A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up
An observational study of Urothelial Carcinoma, run by Changhai Hospital at 1 site in China.
Trial summary
Urothelial carcinoma (UC) is common malignancy and is considered to be one of the costliest cancers. The traditional diagnostic methods of UC present with some shortcomings. For example, the specificity of CTU remains low while cystoscopy is invasive and expensive. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma
- What is being tested?
- The level of CNV
- How many people
- 500 participants
- Where
- 1 siteChina
- Study dates
- 17 Jan 2020to 30 Jun 2022
- 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 from January 2020 to June 2022 in 10 hospitals including Changhai hospital, Renji hospital, The First Affiliated Hospital of Suchow university, Zhejiang Provincial people's hospital, Tongji hospital, The second hospital of Tianjin medical university, Qilu hospital, Second Affiliated Hospital of Sun Yat-Sen University, Xibei hospital, West China hospital.
Who may be able to join
- Patients diagnosed with urothelial carcinoma and planned to undergo surgery
- Cancer patient with urine cytology test result
- Cancer patient willing to provide urine sample before the surgery, 3 months after surgery, 6 months after surgery, 12 month after surgery, 15 months after surgery, 18 months after surgery, 21 months after surgery, 24 months after surgery, and willing to provide patient information.
- 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.
- Patient already received suprapubic cystostomy or urethral catheterization.
- Patient with late-stage uremia and need regular dialysis.
- Patient with cancer other than urothelial carcinoma.
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
Urothelial carcinoma (UC) is common malignancy and is considered to be one of the costliest cancers. The traditional diagnostic methods of UC present with some shortcomings. For example, the specificity of CTU remains low while cystoscopy is invasive and expensive. Therefore, a noninvasive diagnostic method with high accuracy is urgently needed. Our previous study has proved that UroCAD, which is able to detect chromosomal aberrations of the urine exfoliated cells, is a reliable method in diagnosing UC with sensitivity and specificity of 82.5% and 96.9%, respectively. But its potential in UC patient follow-up hasn't been assessed yet and the the accuracy of UroCAD in detecting UC still need to be further validated. The investigators here intended to investigate whether UroCAD can be used in UC patient follow-up and further validate the accuracy of UroCAD in diagnosing UC.
Read the detailed description
The traditional diagnostic methods of UC include CT urography (CTU) and cystoscopy. To access the upper urinary tract, CTU is commonly used. The sensitivity for detecting upper tract urothelial cancer with CTU has been reported to reach 89%. However, the specificity of CTU is 51% and it cannot get a biopsy sample. Other shortcomings include exposing the patient to high dose of radiation and the contrast material usage may impair the renal function. In the context of diagnosing lower urinary tract cancer, cystoscopy is the "gold standard" diagnostic procedure, which has a sensitivity of 68-83%. But it is invasive, uncomfortable and may miss flat lesions. Furthermore, due to the high recurrence rate of bladder cancer, surveillance of the disease with frequent cystoscopy make it one of the costliest cancers. Therefore, a noninvasive diagnostic method with high accuracy is urgently needed.
Copy number variations (CNVs) refers to the ongoing acquisition of genomic alterations ranging from point mutations to gross chromosomal rearrangements, is a hallmark of cancer which is found in 60-80% of human cancer, and it positively correlates with high tumor stage, poor prognosis, metastasis and therapeutic resistance. Several researches have investigated the value of detecting chromosomal instability with sWGS in either cell-free (cf)DNA or genomic DNA as a noninvasive diagnostic method for cancers and yielded quite fine results. Our previous research has also proved the UroCAD model reached performance of AUC=0.928, with sensitivity, specificity and accuracy of 82.5%, 96.9% and 89.0%, respectively. This test also showed superiority in diagnosing upper tract urothelial cancer compared with urinary cytology test.
Here the investigators intended to conduct a prospective, multicenter, single-blinded research to further validate the value of UroCAD in diagnosing UC and investigate the potential of UroCAD in UC patient follow-up by analyzing the CNV level of patient DNA extracted from urine exfoliated cells and follow UC patient for up to 2 years to determine if there is a correlation between CNV level and patient prognosis. Patient information, which is acquired every 3 months after surgery, including survival status, CNV level in urine exfoliated cells, treatment during this period, medical examination during this period, etc.
- Conditions
- Urothelial Carcinoma
- Being tested
- The level of CNV
- Keywords
- diagnosis, follow-up
- Medical subject headings
- Carcinoma, Transitional Cell, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The level of CNVDiagnostic test
Also called UroCAD test of the urine exfoliated cells
The extracted DNA from morning urine will be analyzed by UroCAD to determine the level of CNV. And the patient will be followed for up to 2 years.
| 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 UroCAD analysis, the result will be compared with cytology and FISH test. Receives: Diagnostic Test: The level of CNV | |
| Non-cancer participants | 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 UroCAD analysis. Receives: Diagnostic Test: The level of CNV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity and Specificity of urinalysis by UroCAD analysis
number of patients "declared positive" with the UroCAD test among the patients suffered from urothelial carcinoma and number of patients "declared negative" with the UCAD test among the patients without cancer.
Measured: through study completion, an average of 30 months
Assess the value of UroCAD for urothelial cancer patient follow-up
Compare the CNV level with the patient information gathered by follow-up to determine whether there is a correlation between CNV level and patient prognosis or disease progression
Measured: through study completion, an average of 30 months
Secondary outcomes (3)
Identification of the correlation between the level of CNV and the grade of the tumor sample
level of CNV in the urine sample compared with the grade of the tumor confirmed by histopathologic examination
Measured: through study completion, an average of 30 months
Identification of the correlation between the level of CNV and the stage of the tumor sample
level of CNV in the urine sample compared with the stage of the tumor confirmed by histopathologic examination
Measured: through study completion, an average of 30 months
Comparison of the sensitivity and specificity of the UroCAD analysis versus urine cytology
number of patients "declared positive" with the UroCAD analysis versus patients "declared positive" with the urine cytology and number of patients "declared negative" with the UroCAD analysis versus patients " declared negative " with the urine cytology
Measured: through study completion, an average of 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start17 Jan 2020
- Primary completion30 Jan 2022 (estimated)
- Study completion30 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changhai Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- RenJi Hospital, The First Affiliated Hospital of Soochow University, Zhejiang Provincial People's Hospital, Tongji Hospital, Tianjin Medical University Second Hospital, Qilu Hospital of Shandong University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Xibei Hospital, West China Hospital
- Responsible party
- Principal investigator, Shuxiong Zeng, Changhai Hospital
- Investigators
- Chuanliang Xu, M.D.,Ph.D., Study chair, Changhai Hospital, Shanghai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04432909
- Sponsor's protocol ID
- CH-urothelial-cancer-marker
- Status last verified
- Sep 2021
- First submitted
- 12 Jun 2020
- Last updated
- 16 Sep 2021
- Results posted
- 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 30178746
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up
- ClinicalTrials.gov ID
- NCT04432909
- Acronym / sponsor ID
- CH-urothelial-cancer-marker
- Conditions
- Urothelial Carcinoma
- Keywords
- diagnosis, follow-up
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Changhai HospitalUniversity, hospital or other
- Collaborators
- RenJi Hospital, The First Affiliated Hospital of Soochow University, Zhejiang Provincial People's Hospital, Tongji Hospital, Tianjin Medical University Second Hospital, Qilu Hospital of Shandong University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Xibei Hospital, West China Hospital
- Study start
- 17 Jan 2020 (actual)
- Primary completion
- 30 Jan 2022 (estimated)
- Study completion
- 30 Jun 2022 (estimated)
- First posted
- 16 Jun 2020 (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.
Urothelial carcinoma (UC) is common malignancy and is considered to be one of the costliest cancers. The traditional diagnostic methods of UC present with some shortcomings. For example, the specificity of CTU remains low while cystoscopy is invasive and expensive. Therefore, a noninvasive diagnostic method with high accuracy is urgently needed. Our previous study has proved that UroCAD, which is able to detect chromosomal aberrations of the urine exfoliated cells, is a reliable method in diagnosing UC with sensitivity and specificity of 82.5% and 96.9%, respectively. But its potential in UC patient follow-up hasn't been assessed yet and the the accuracy of UroCAD in detecting UC still need to be further validated. The investigators here intended to investigate whether UroCAD can be used in UC patient follow-up and further validate the accuracy of UroCAD in diagnosing UC.
Detailed description
The traditional diagnostic methods of UC include CT urography (CTU) and cystoscopy. To access the upper urinary tract, CTU is commonly used. The sensitivity for detecting upper tract urothelial cancer with CTU has been reported to reach 89%. However, the specificity of CTU is 51% and it cannot get a biopsy sample. Other shortcomings include exposing the patient to high dose of radiation and the contrast material usage may impair the renal function. In the context of diagnosing lower urinary tract cancer, cystoscopy is the "gold standard" diagnostic procedure, which has a sensitivity of 68-83%. But it is invasive, uncomfortable and may miss flat lesions. Furthermore, due to the high recurrence rate of bladder cancer, surveillance of the disease with frequent cystoscopy make it one of the costliest cancers. Therefore, a noninvasive diagnostic method with high accuracy is urgently needed.
Copy number variations (CNVs) refers to the ongoing acquisition of genomic alterations ranging from point mutations to gross chromosomal rearrangements, is a hallmark of cancer which is found in 60-80% of human cancer, and it positively correlates with high tumor stage, poor prognosis, metastasis and therapeutic resistance. Several researches have investigated the value of detecting chromosomal instability with sWGS in either cell-free (cf)DNA or genomic DNA as a noninvasive diagnostic method for cancers and yielded quite fine results. Our previous research has also proved the UroCAD model reached performance of AUC=0.928, with sensitivity, specificity and accuracy of 82.5%, 96.9% and 89.0%, respectively. This test also showed superiority in diagnosing upper tract urothelial cancer compared with urinary cytology test.
Here the investigators intended to conduct a prospective, multicenter, single-blinded research to further validate the value of UroCAD in diagnosing UC and investigate the potential of UroCAD in UC patient follow-up by analyzing the CNV level of patient DNA extracted from urine exfoliated cells and follow UC patient for up to 2 years to determine if there is a correlation between CNV level and patient prognosis. Patient information, which is acquired every 3 months after surgery, including survival status, CNV level in urine exfoliated cells, treatment during this period, medical examination during this period, etc.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Urothelial carcinoma group | – | Diagnostic Test: The level of CNVPre-surgery patients with urothelial carcinoma will be the experimental group to determine the sensitivity and specificity of UroCAD analysis, the result will be compared with cytology and FISH test. |
| Non-cancer participants | – | Diagnostic Test: The level of CNVPatients being treated for other diseases but without any tumor will provide a negative control to provide data for determining the sensitivity and specificity of UroCAD 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 from January 2020 to June 2022 in 10 hospitals including Changhai hospital, Renji hospital, The First Affiliated Hospital of Suchow university, Zhejiang Provincial people's hospital, Tongji hospital, The second hospital of Tianjin medical university, Qilu hospital, Second Affiliated Hospital of Sun Yat-Sen University, Xibei hospital, West China hospital.
Key inclusion criteria (6 listed)
- Patients diagnosed with urothelial carcinoma and planned to undergo surgery
- Cancer patient with urine cytology test result
- Cancer patient willing to provide urine sample before the surgery, 3 months after surgery, 6 months after surgery, 12 month after surgery, 15 months after surgery, 18 months after surgery, 21 months after surgery, 24 months after surgery, and willing to provide patient information.
- Participants without any tumor disease and willing to attend the study by providing morning urine.
- Male or female patients aged >= 18 years.
Key exclusion criteria (5 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.
- Patient already received suprapubic cystostomy or urethral catheterization.
- Patient with late-stage uremia and need regular dialysis.
- Patient with cancer other than urothelial carcinoma.
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 |
|---|---|---|
| The level of CNVAlso: UroCAD test of the urine exfoliated cellsThe extracted DNA from morning urine will be analyzed by UroCAD to determine the level of CNV. And the patient will be followed for up to 2 years. | Diagnostic test | Non-cancer participants, Urothelial carcinoma group |
Primary outcome
Sensitivity and Specificity of urinalysis by UroCAD analysis
Time frame: through study completion, an average of 30 months
number of patients "declared positive" with the UroCAD test among the patients suffered from urothelial carcinoma and number of patients "declared negative" with the UCAD test among the patients without cancer.
Assess the value of UroCAD for urothelial cancer patient follow-up
Time frame: through study completion, an average of 30 months
Compare the CNV level with the patient information gathered by follow-up to determine whether there is a correlation between CNV level and patient prognosis or disease progression
3 secondary outcomes
Identification of the correlation between the level of CNV and the grade of the tumor sample
Time frame: through study completion, an average of 30 months
Identification of the correlation between the level of CNV and the stage of the tumor sample
Time frame: through study completion, an average of 30 months
Comparison of the sensitivity and specificity of the UroCAD analysis versus urine cytology
Time frame: through study completion, an average of 30 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2021.
- 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.
- 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.
Chuanliang Xu, M.D.,Ph.D. study chair
Changhai Hospital, Shanghai
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, 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 6 inclusion and 5 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 16 Sep 2021. 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 and Specificity of urinalysis by UroCAD analysis (time frame: through study completion, an average of 30 months). 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 NCT04432909, which also lists 4 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 16 Sep 2021.