Clinical trial NCT05237193: A Prospective Study of UCAD for Diagnosing Benign or Malignant Biliary Obstruction and Follow-up
Official title: A Prospective, Multi-centre, Single-blinded Study of UCAD for Diagnosing Benign or Malignant Biliary Obstruction and Follow-up
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Biliary Tract Neoplasms
Pancreatic Carcinoma
Gallbladder Cancer
Pancreatic Head Carcinoma
Keywords: diagnosis
follow-up
Lead sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Shanghai Zhongshan Hospital
name: Ruijin Hospital
name: Changhai Hospital
name: Shanghai Changzheng Hospital
name: Eastern Hepatobiliary Surgery Hospital
name: First Affiliated Hospital Xi'an Jiaotong University
name: Jiangsu Provincial People's Hospital
name: Third Affiliated Hospital, Sun Yat-Sen University
name: First Affiliated Hospital of Zhejiang University
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Second Hospital of Jilin University
name: West China Hospital
name: Southwest Hospital, China
name: Afﬁliated Hospital of North Sichuan Medical College
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
First posted: 2022-02-14
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with malignant biliary obstruction or participants in control group from February 2022 till the end of this study in 11 hospitals including Xinhua Hospital, Shanghai Zhongshan Hospital, Ruijin Hospital, Changhai Hospital, Shanghai Changzheng Hospital, Eastern Hepatobiliary Surgery Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Jiangsu Provincial Hospital, The Third Affiliated Hospital of Sun Yat-Sen University, Tianjin Medical University Second Hospital, First Affiliated Hospital of Zhejiang University.

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 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.

Detailed 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

Eligibility criteria: 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.

Primary outcomes:
measure: Sensitivity and Specificity of UCAD analysis
timeFrame: through study completion, an average of 30 months
measure: Assess the value of UCAD for malignant biliary obstruction patient follow-up
timeFrame: through study completion, an average of 30 months
Secondary outcomes:
measure: Identification of the correlation between the level of CIN and the grade of the tumor sample
timeFrame: through study completion, an average of 30 months
measure: Identification of the correlation between the level of CIN and the stage of the tumor sample
timeFrame: through study completion, an average of 30 months
measure: Comparison of the sensitivity and specificity of the UCAD analysis versus bile cytology
timeFrame: through study completion, an average of 30 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Xinhua Hospital
state: Shanghai
Study officials:
affiliation: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Jiandong Jiandong, M.D., Ph.D.
role: STUDY_CHAIR
References:
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.
citation: 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.