NGS in Gallbladder Cancer and Response to Treatment

August 9, 2024 updated by: Manoj Pandey, Banaras Hindu University

Genetic Mutations and Response to Treatment in Gallbladder Cancer: A Hospital Based Cohort Study

Evidence suggests distinct models of molecular and pathologic progression, and a growing body of genetics data points to a heterogeneous collection of underlying mutations in key oncogenes and tumor suppressor genes. Although tumor genetics have been used to tailor individual treatment regimens and guide clinical decision making in other cancers, these principles have not been applied in gallbladder malignancy. Recent clinical trials with targeted therapies seem promising, although the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Gallbladder carcinoma (GBC) is the most common type of biliary tract carcinoma and the third commonest digestive tract malignancy in India. GBC arises in the setting of chronic inflammation and the commonest source is cholesterol gallstones (in more than 75% patients). Other causes of chronic inflammation include primary sclerosing cholangitis, ulcerative colitis, liver flukes, chronic Salmonella typhi and paratyphi infections, and Helicobacter infection. Many other factors have also been identified such as ingestion of certain chemicals, exposures through water pollution, heavy metals and radiation exposure. Only a small fraction of GBC are associated with hereditary syndromes like Gardner syndrome, neurofibromatosis type I and hereditary non-polyposis colon cancer.

Of the multiple molecular alterations observed in GBC, it has not yet been possible to pinpoint which ones are the "driver" genes or controllers of the neoplastic process and to differentiate them from the "passenger" genes, those observed mainly in sporadic malignant tumors like GBC in which epigenetic alterations predominate. The most frequently mutated genes in GBC are: TP53 (41%), CDKN2A (28%) KRAS (19%), TERT (8%), CTNNB1 (8%) and PI3K (7%). The signalling pathway of the ERBB family is one of the most frequently mutated in GBC. These receptors participate in regulating cell proliferation, differentiation and survival. Their amplification mainly translates into protein over expression. The receptor HER2/NEU, after dimerization activates a large variety of downstream pathways such as RAS-RAF-MEK-ERK1/2 or PI3k-AKT-MTOR with great influence on cell proliferation. On the other hand, PTEN (phosphatase and tensin homolog) is a tumor suppressor gene that encodes a protein with phosphatase function that inactivates substrates like PI3K The absence of the PTEN functional protein permits the activation of PI3k with an even greater intensity than the activating mutation of PI3K itself. The uncontrolled production of PIP3 is one of the most important effectors of the PI3K/AKT pathway with mTOR stimulating protein synthesis that regulate apoptosis. The immunohistochemical expression of the PTEN protein is considered a good way to evaluate the functional state of the gene.

  1. Comprehensive history and physical examination of the patients and all the details will be recorded in the preset proforma. All routine investigations as indicated including a biopsy to establish a diagnosis and CT/MRI/MRCP of the abdomen to measure the tumor dimensions and stage the disease before initiation of treatment will be recorded.
  2. The archival tissue will be studied for expression of gene mutation by molecular analysis using Next Generation Sequencing. Patients treated between 2017-2020 where NGS information is available will also be included in retrospect. Their data will be extracted from the Medical records, and attempts will be made to contact them for follow-up.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with histologically confirmed diagnosis of gallbladder cancer irrespective of stage, being treated with palliative or curative intent with standard of care for that stage of carcinoma of the gallbladder

Description

Inclusion Criteria:

  • Treatment naïve patients with histologically proven carcinoma of the gallbladder.

Exclusion Criteria:

  • No histological evidence of malignancy
  • Pregnant and lactating women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Gallbladder Cancer
Patients with confirmed diagnosis of gallbladder cancer
Diagnostic test: Next generation sequencing
NGS is carried out on DNA isolated from paraffin embedded tissue

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response to treatment
Time Frame: 1 year
Response to treatment in terms of chemotherapy
1 year
Overall Survival
Time Frame: 5 year
Survival of patients from the date of diagnosis to closure of study or death which ever is earlier
5 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: 5 yers
Progression free survival from the date of diagnosis to progression of disease
5 yers
RFS
Time Frame: 5 year
Recurrence free Survival from the date of diagnosis to occurrence of recurrence or metastasis
5 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Banaras Hindu University

Investigators

  • Principal Investigator: Manoj Pandey, MS, PhD, Banaras Hindu University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2018

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

May 31, 2022

First Submitted That Met QC Criteria

May 31, 2022

First Posted (Actual)

June 3, 2022

Study Record Updates

Last Update Posted (Actual)

August 13, 2024

Last Update Submitted That Met QC Criteria

August 9, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NGSGB1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized data will be made available on reasonable request

IPD Sharing Time Frame

3 months

IPD Sharing Access Criteria

Request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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