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NGS in Gallbladder Cancer and Response to Treatment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05404347
Recruitment Status : Recruiting
First Posted : June 3, 2022
Last Update Posted : June 6, 2022
Sponsor:
Information provided by (Responsible Party):
Manoj Pandey, Banaras Hindu University

Brief Summary:
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.

Condition or disease Intervention/treatment
Gallbladder Cancer Diagnostic Test: Next generation sequencing

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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
Official Title: Genetic Mutations and Response to Treatment in Gallbladder Cancer: A Hospital Based Cohort Study
Actual Study Start Date : January 1, 2018
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Response to treatment [ Time Frame: 1 year ]
    Response to treatment in terms of chemotherapy

  2. Overall Survival [ Time Frame: 5 year ]
    Survival of patients from the date of diagnosis to closure of study or death which ever is earlier


Secondary Outcome Measures :
  1. PFS [ Time Frame: 5 yers ]
    Progression free survival from the date of diagnosis to progression of disease

  2. RFS [ Time Frame: 5 year ]
    Recurrence free Survival from the date of diagnosis to occurrence of recurrence or metastasis


Biospecimen Retention:   Samples With DNA
Paraffin embedded tissue


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • No histological evidence of malignancy
  • Pregnant and lactating women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05404347


Contacts
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Contact: Manoj Pandey, MS, PhD mpandey66@bhu.ac.in
Contact: S K Singh, MD, DM 2361014 mdean.ims@gmail.com

Locations
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India
Banaras Hindu University Recruiting
Varanasi, UP, India, 221005
Contact: Manoj Pandey, MS, PhD    2361014    mpandey66@bhu.ac.in   
Contact: Manoj Pandey, MS, PhD       mpandey66@bhu.ac.in   
Sponsors and Collaborators
Banaras Hindu University
Investigators
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Principal Investigator: Manoj Pandey, Ms, PhD Banaras Hindu University
Publications of Results:
Rajput M, Chigurupati SJ, Purwar R, Shukla M, Pandey M: MAP Kinase and mammalian target of rapamycin are main pathways of gallbladder carcinogenesis: Results from bioinformatic analysis of Next Generation Sequencing data from a hospital-based cohort. bioRxiv 2022.05.11.491590; doi: https://doi.org/10.1101/2022.05.11.491590

Other Publications:

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Responsible Party: Manoj Pandey, Professor, Banaras Hindu University
ClinicalTrials.gov Identifier: NCT05404347    
Other Study ID Numbers: NGSGB1
First Posted: June 3, 2022    Key Record Dates
Last Update Posted: June 6, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized data will be made available on reasonable request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: 3 months
Access Criteria: Request

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Gallbladder Neoplasms
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases