NCT03998371

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started May 2019

Shorter than P25 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 5, 2019

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

June 19, 2019

Completed
7 days until next milestone

First Posted

Study publicly available on registry

June 26, 2019

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 5, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 5, 2020

Completed
Last Updated

June 26, 2019

Status Verified

June 1, 2019

Enrollment Period

1 year

First QC Date

June 19, 2019

Last Update Submit

June 25, 2019

Conditions

Urothelial CarcinomaDiagnoses DiseaseChromosomal AbnormalityUrine Marking

Keywords

Urothelial CarcinomadiagnosisChromosomal Aneuploidy Detectionmarkerurine

Outcome Measures

Primary Outcomes (2)

  • 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

  • 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 Outcomes (2)

  • Comparison of the sensitivity of the UCAD analysis versus urine cytology

    Up to 1 years

  • Comparison of the specificity of the UCAD analysis versus urine cytology

    Up to 1 years

Other Outcomes (2)

  • Identification of the correlation between the level of CIN and the grade of the tumor sample

    Up to 1 years

  • Identification of the correlation between the level of CIN and the stage of the tumor sample

    Up to 1 years

Study Arms (2)

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.

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.

Diagnostic Test: Low-coverage whole-genome sequencing of urine exfoliated cells

Interventions

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.

Non-cancer participants groupUrothelial carcinoma group

Eligibility Criteria

Age18 Years+
Sexall
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Patients diagnosed with urothelial carcinoma or participants in control group in Changhai Hospital from May 2019 till the end of this study.

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Changhai Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

Related Publications (5)

  • 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.

    PMID: 24346386BACKGROUND

  • 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.

    PMID: 29342134BACKGROUND

  • 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.

    PMID: 29907142BACKGROUND

  • 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:e37294. doi: 10.7554/eLife.37294.

    PMID: 30178746BACKGROUND

  • Zeng 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.

    PMID: 33037018DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA from Urine Exfoliated Cells will be analyzed by Ultrasensitive Chromosomal Aneuploidy Detection

MeSH Terms

Conditions

Carcinoma, Transitional CellChromosome AberrationsDisease

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Chuangliang Xu, M.D., Ph.D

    Changhai Hospital

    STUDY CHAIR

Central Study Contacts

Shuxiong zeng, M.D., Ph.D

CONTACT

+8618930568759zengshuxiong@126.com

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

June 19, 2019

First Posted

June 26, 2019

Study Start

May 5, 2019

Primary Completion

May 5, 2020

Study Completion

May 5, 2020

Last Updated

June 26, 2019

Record last verified: 2019-06

Data Sharing

IPD Sharing
Will not share

We will try to protect the information of the included participants

Locations

CN(1)