A Prospective Study of UCAD for Diagnosing Benign or Malignant Biliary Obstruction and Follow-up

Gallbladder Cancer Clinical Trial

Official title:

A Prospective, Multi-centre, Single-blinded Study of UCAD for Diagnosing Benign or Malignant Biliary Obstruction and Follow-up

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05237193
• Other study ID #: XH-22-001
• Status: Recruiting
• Start date: September 3, 2021
• Est. completion date: March 2024

Study information

• Verified date: May 2022
• Source: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: Jiandong Wang, M.D., Ph.D.
• Phone: +86 13801932014
• Email: wangjiandongdr[@]163.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 bile tract exfoliated cells in bile samples seems a promising method for diagnosing, monitoring, and predicting the prognosis of patients with malignant biliary obstruction, including biliary tract cancer (BTC), pancreatic head carcinoma. 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. The investigators 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 helping diagnose malignant biliary obstruction and assessing follow-up.

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 to 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 bile tract exfoliated cells in bile samples for diagnosing and monitoring malignant biliary obstruction patients. UCAD is a new method to detect CIN in the DNA sample from patients, including extracting DNA from bile, analyzing DNA by low-coverage whole-genome sequencing, processing the data by bio-information techniques, and finally optimizing the management of malignant biliary obstruction patients. The investigators intended to conduct a prospective, single-blinded study by analyzing bile samples from malignant biliary obstruction patients and control groups without any tumor in the biliary system or other organs to compare the specificity and sensitivity of the UCAD test for diagnosing malignant biliary obstruction to other modalities, such as bile cytology. The investigators also intend to investigate the potential of UCAD in malignant biliary obstruction patient follow-up by analyzing the CIN level and following malignant biliary obstruction patients for up to 2 years to determine if there is a correlation between CIN level and patient prognosis

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: March 2024
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients diagnosed with malignant biliary obstruction and planned to undergo ERCP(endoscopic retrograde cholangiopancreatography), PTCS(percutaneous transhepatic cholangioscopy) or surgery.

• Malignant biliary obstruction patients confirmed by operation or biopsy.

• Participants without any tumor disease and willing to attend the study.

• Male or female patients aged >= 18 years.

• Participants signed informed consent form.

Exclusion Criteria:

• Patients diagnosed with malignant biliary obstruction and planned to undergo ERCP, PTCS or surgery.

• Malignant biliary obstruction patients confirmed by operation or biopsy.

• Participants without any tumor disease and willing to attend the study.

• Male or female patients aged >= 18 years.

• Participants signed informed consent form.

Related Conditions & MeSH terms

• Biliary Tract Neoplasms
• Carcinoma
• Gallbladder Cancer
• Gallbladder Neoplasms
• Pancreatic Carcinoma
• Pancreatic Neoplasms

Intervention

Diagnostic Test:
• The level of CIN
The extracted DNA from bile will be analyzed by UCAD to determine the level of CIN. And the patient will be followed for up to 2 years.

Locations

Country	Name	City	State
China	Xinhua Hospital	Shanghai	Shanghai

Sponsors (16)

Lead Sponsor

Collaborator

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Af?liated Hospital of North Sichuan Medical College, Changhai Hospital, Eastern Hepatobiliary Surgery Hospital, First Affiliated Hospital of Zhejiang University, First Affiliated Hospital Xi'an Jiaotong University, Jiangsu Provincial People's Hospital, Ruijin Hospital, Second Hospital of Jilin University, Shanghai Changzheng Hospital, Shanghai Zhongshan Hospital, Southwest Hospital, China, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Third Affiliated Hospital, Sun Yat-Sen University, West China Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

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:e37294. doi: 10.7554/eLife.37294. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity and Specificity of UCAD analysis	number of patients "declared positive" with the UCAD test among the patients who suffered from malignant biliary obstruction and number of patients "declared negative" with the UCAD test among the patients without cancer	through study completion, an average of 30 months
Primary	Assess the value of UCAD for malignant biliary obstruction patient follow-up	Compare the CIN level with the patient information gathered by follow-up to determine whether there is a correlation between CIN level and patient prognosis , like PFS(progression-free survival), five-year survival rate.	through study completion, an average of 30 months
Secondary	Identification of the correlation between the level of CIN and the grade of the tumor sample	level of CIN in the bile sample compared with the grade of the tumor confirmed by histopathologic examination, like Grade 1-4.	through study completion, an average of 30 months
Secondary	Identification of the correlation between the level of CIN and the stage of the tumor sample	level of CIN in the bile sample compared with the TNM stage of the tumor confirmed by histopathologic examination, like Stage 0-IV.	through study completion, an average of 30 months
Secondary	Comparison of the sensitivity and specificity of the UCAD analysis versus bile cytology	number of patients "declared positive" with the UCAD analysis versus patients "declared positive" with the bile cytology and number of patients "declared negative" with the UCAD analysis versus patients " declared negative " with the bile cytology	through study completion, an average of 30 months