A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up

• ClinicalTrials.gov Identifier: NCT04432909
• Recruitment Status: Recruiting
• First Posted: June 16, 2020
• Last Update Posted: June 16, 2020
• Sponsor: Changhai Hospital
• 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
• Information provided by (Responsible Party): Shuxiong Zeng, Changhai Hospital

Study Description

Brief Summary:

Urothelial carcinoma (UC) is common malignancy and is considered to be one of the most expensive 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. We here intended to investigate whether UroCAD can be used in UC patient follow-up and further validate the accuracy of UroCAD in diagnosing UC.

Condition or disease	Intervention/treatment
Urothelial Carcinoma	Diagnostic Test: The level of CNV

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 we 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

• Study Type: Observational
• Estimated Enrollment: 500 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up
• Actual Study Start Date: January 17, 2020
• Estimated Primary Completion Date: January 30, 2022
• Estimated Study Completion Date: June 30, 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
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.	Diagnostic Test: The level of CNV; 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.; Other Name: UroCAD test of the urine exfoliated cells
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.	Diagnostic Test: The level of CNV; 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.; Other Name: UroCAD test of the urine exfoliated cells

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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

Secondary Outcome Measures :

1. 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 ]
   level of CNV in the urine sample compared with the grade of the tumor confirmed by histopathologic examination
2. 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 ]
   level of CNV in the urine sample compared with the stage of the tumor confirmed by histopathologic examination
3. Comparison of the sensitivity and specificity of the UroCAD analysis versus urine cytology [ Time Frame: through study completion, an average of 30 months ]
   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

Biospecimen Retention:   Samples With DNA

DNA from Urine Exfoliated Cells will be analyzed

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Sampling Method: Non-Probability Sample

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.

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Contacts and Locations

Contacts

Contact: Shuxiong Zeng, M.D., Ph.D.; +8618930568759; zengshuxiong@126.com

Locations

China, Shanghai

Changhai Hospital; Recruiting

Shanghai, Shanghai, China, 200433

Contact: Shuxiong Zeng, M.D. Ph.D +8618930568759 zengshuxiong@126.com

Sponsors and Collaborators

Changhai Hospital

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

Investigators

• Study Chair: Chuanliang Xu, M.D.,Ph.D.; Changhai Hospital, Shanghai

More Information

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. Review.

Bakhoum 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.

Liu 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.

Hieronymus 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. pii: e37294. doi: 10.7554/eLife.37294.

• Responsible Party: Shuxiong Zeng, Ph.D, M.D., Changhai Hospital
• ClinicalTrials.gov Identifier: NCT04432909
• Other Study ID Numbers: CH-urothelial-cancer-marker
• First Posted: June 16, 2020
• Last Update Posted: June 16, 2020
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: We will try to protect the information of the included participants

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shuxiong Zeng, Changhai Hospital:

diagnosis; follow-up

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Transitional Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms