Application of UCAD for Diagnosing Urothelial Carcinoma.

Urothelial Carcinoma Clinical Trial

Official title:

Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) in Urine Exfoliated Cells for Diagnosis of Urothelial Carcinoma in in Urine Exfoliated Cells

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03998371
• Other study ID #: CH-urology-bladder marker-002
• Status: Recruiting
• Start date: May 5, 2019
• Est. completion date: May 5, 2020

Study information

• Verified date: June 2019
• Source: Changhai Hospital
• Contact: Shuxiong zeng, M.D., Ph.D
• Phone: +8618930568759
• Email: zengshuxiong[@]126.com
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: May 5, 2020
• Est. primary completion date: May 5, 2020
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

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.

• Individuals unwilling to participate in this trial.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Chromosomal Abnormality
• Chromosome Aberrations
• Chromosome Disorders
• Diagnoses Disease
• Urine Marking
• Urothelial Carcinoma

Intervention

Diagnostic Test:
• Low-coverage whole-genome sequencing of urine exfoliated cells
The level of CIN The extracted DNA from morning urine will be analyzed by UCAD to determine the level of CIN.

Locations

Country	Name	City	State
China	Changhai Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Changhai Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Identification of the correlation between the level of CIN and the grade of the tumor sample	Level of CIN in the urine sample compared with the grade of the tumor confirmed by histopathologic examination	Up to 1 years
Other	Identification of the correlation between the level of CIN and the stage of the tumor sample	Level of CIN in the urine sample compared with the stage of the tumor confirmed by histopathologic examination.	Up to 1 years
Primary	Sensitivity of urinalysis by UCAD analysis	Number of patients "declared positive" with the UCAD test among the patients suffered from urothelial carcinoma.	Up to 1 years
Primary	Specificity of urinalysis by UCAD analysis	Number of patients "declared negative" with the UCAD test among the patients without cancer.	Through study completion, an average of 12 months
Secondary	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.	Up to 1 years
Secondary	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.	Up to 1 years