Molecular Basis of Pediatric Liver Cancer

Genetic and Molecular Basis of Pediatric Liver Cancer

The purpose of this retrospective and prospective project is to understand the molecular and genetic basis of liver cancer of childhood. Understanding the molecular and genetic bases of liver cancers can offer a better classification based on tumor biology, mechanisms and predisposition.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma; Hepatoblastoma; Rhabdoid Tumor of Liver; Childhood Liver Cancer; Liver Malignant Tumors; Embryonal Sarcoma of Liver (Disorder)

Detailed Description

Pediatric liver cancers are rare, affecting at times no more than 1 in one million population. Understanding the molecular basis of these cancers is important in order to develop more accurate diagnoses and more effective treatments. Current classifications of these cancers are based on how these cancers look on diagnostic studies such as radiologic imaging or under the microscope. Such a classification system does not explain why a particular cancer has a different outcome from what is considered "usual" for that particular cancer. Nor does such a classification system explain why two different classes of cancers behave the same way. Understanding the genetic bases of liver cancers can offer a better classification based on tumor biology, mechanisms and predisposition.

To achieve these goals, large numbers of such cancer patients or affected tissue must be collected. This is not possible in any single institution, or any single country. The current project will collect biological samples such as residual tumor tissue, saliva, or blood from affected patients and their biological parents and families, along with clinical information about the cancer. These biological samples will be used to study the genes and how these genes work in tumor tissue and in non-tumor tissue. The results of this study will permit childhood liver cancers to be categorized on the basis of common defects in genes and their function.

• Study Type: Observational
• Enrollment (Estimated): 1600

Contacts and Locations

• Study Contact: Name: Morgan Paul, BSN; Phone Number: (412) 692-8472; Email: Morgan.Paul2@upmc.edu
• Study Contact Backup: Name: Daniel Pieratt, MPA; Phone Number: (412) 692-6692; Email: pierattdw@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • UPMC Children's Hospital of Pittsburgh
      • Contact: Morgan L Paul, BSN; Phone Number: 412-692-8472; Email: Morgan.Paul2@upmc.edu
      • Principal Investigator: Rakesh Sindhi, MD
      • Contact: Daniel Pieratt, MPA; Phone Number: 4126926692; Email: pierattdw@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Living or deceased individuals who were diagnosed with a liver tumor, malignant or benign, during childhood (age <21 years) and their biological parents and siblings.

Description

Inclusion Criteria:

• Prior or current treatment for a childhood liver tumor, malignant or benign, at age <21 years.
• Biological parents and siblings of eligible children.

Exclusion Criteria:

• No prior or current treatment for a childhood liver tumor.
• Non-biological parents, legal guardians, or non-biological siblings of eligible children.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene sequencing	DNA sequence variants	Recurrence free survival at 2 years
Gene expression analysis	Differentially expressed genes	Recurrence free survival at 2 years
Status of genome-wide chromatin accessibility	chromatin accessibility	Duration of active chemotherapy to two years after surgical treatment
Epigenetic change	Differential methylation	Duration of active chemotherapy to two years after surgical treatment
Tumor infiltrating cells which express immune checkpoints	differentially enriched immune cells	Duration of active chemotherapy to two years after surgical treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to chemotherapy	Survival	Duration of active chemotherapy to two years after surgical treatment
Response to chemotherapy	Relapse	Duration of active chemotherapy to two years after surgical treatment

Collaborators and Investigators

• Sponsor: University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2015
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: May 15, 2019
• First Submitted That Met QC Criteria: May 21, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Hepatoblastoma; Pediatric Liver Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Neoplasms, Complex and Mixed; Carcinoma, Hepatocellular; Rhabdoid Tumor; Liver Neoplasms; Hepatoblastoma
• Other Study ID Numbers: STUDY20050018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No