A Study of Molecular and Genetic Factors for Liver Cancer in the Greater Baltimore Area

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00913757
First received: June 3, 2009
Last updated: October 11, 2014
Last verified: September 2014
  Purpose

Background:

  • Liver cancer is the third most deadly and fifth most common cancer worldwide. Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, and it has grown more prevalent in the United States.
  • More information is needed about the causes and effects of liver cancer, and further research into individuals who are at high risk for developing liver cancer is needed for early diagnosis and prevention.

Objectives:

  • To identify genetic factors that may help to explain the aggressiveness of liver cancer.
  • To determine if HCC biomarkers exist in blood, urine, and tissue samples.

Eligibility:

  • Patients between the ages of 18 and 90 who have been diagnosed with HCC or have a high risk for developing HCC because of fatty liver disease (alcohol-related or non-alcohol-related) or chronic hepatitis B or C.
  • Participants will reside in Baltimore City and the surrounding areas.

Design:

  • Participants will complete a questionnaire and provide blood and urine samples for testing:
  • The questionnaire will include questions about individual and family medical history, tobacco use, and exposure to known factors for liver cancer.
  • Blood and urine samples will be collected from all participants after the questionnaire.
  • Tumor tissue and healthy tissue will be collected from selected participants if they undergo surgery for their cancer or disease.
  • No specific treatment will be offered as part of this protocol, but participants have the option to be treated under different protocols.

Condition
Carcinoma, Hepatocellular
Liver Cirrhosis, Alcoholic
Hepatitis, Alcoholic
Hepatitis, Chronic
Hepatitis, Viral, Human

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: A Study of Molecular and Genetic Factors for Liver Cancer in the Greater Baltimore Area

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Large-scale molecular profiling study to identify HCC biomarkers forearly diagnosis and prevention. [ Time Frame: duration of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 1500
Study Start Date: May 2009
Detailed Description:

BACKGROUND:

Liver cancer is the third most deadly and fifth most common cancer worldwide. Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver with rising incidence in the United States. HCC patients have a dismal outcome and are an underserved cancer population. We are proposing a liver cancer case-control and case-case study to be conducted in Baltimore, Maryland.

OBJECTIVES:

Our research is aimed to identify genetic and genomic changes that might explain the aggressive nature of liver cancer. We will test the primary hypothesis that HCC biomarkers exist in blood products (or mouth wash), urine and/or tissues that can be used for early diagnosis and prevention. A unique study factor is the use of urine samples for biomarker identification. A secondary goal will be to examine whether certain genetic and genomic factors modify liver cancer susceptibility using candidate and genome wide association study approaches. Although other studies have investigated genetic susceptibility, large scale studies have not been conducted for liver cancer. Our study will also be valuable due to access to frozen tumor specimens from pre-therapy resection, whose collection is required for gene expression analysis. If certain genes are related to HCC risk and progression, this tissue resource will be used to further validate our findings with laboratory investigations. The proposed study is designed to be exploratory and hypothesis generating.

ELIGIBILITY:

The participants will reside in Baltimore City and surrounding areas. Cases will have pathologically confirmed liver cancer or risk factors for HCC development. Risk factors include chronic liver disease due to hepatitis B and/or C viral infection, nonalcoholic steatohepatitis or alcoholic cirrhosis. The study will be supported by an epidemiological infrastructure developed by our University of Maryland School of Medicine resource contractor for ongoing lung and prostate cancer case-control studies. The enrollment of controls will begin concurrently with case accrual, and will continue for 5 years. Population-based controls will be recruited using a triple eligibility criterion, such that controls eligible for the lung/prostate study will be asked to complete a supplemental questionnaire for the liver study.

DESIGN:

The study will include 250 primary HCC cases, 500 patients with chronic liver disease (high risk non-cancer cases) and a sample of 750 population-based controls. The HCC and high risk non-cancer cases will be recruited at three Baltimore hospitals, the Veterans Affairs Medical Center, the University of Maryland School of Medicine and the Johns Hopkins Medical Institute, over a period of 5 years. Controls will be identified through a Department of Motor Vehicle database and match cases by age, gender, race and county of residency. The study will involve administration of a questionnaire and collection of blood (or mouth wash) from all study subjects. Fresh-frozen tumor and tumor surrounding non-cancerous specimens will be obtained from approximately 20 percent of the cancer patients. The cases will receive one questionnaire. The first 12 months will constitute a pilot study, during which we will evaluate and refine recruitment procedures.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

SELECTION OF CASE SUBJECTS (HCC AND HIGH RISK NON-CANCER CASES)

We will recruit incident cases of pathologically confirmed primary liver cancer or risk factors for liver cancer (patients with chronic liver disease due to hepatitis B and/or C viral infection, nonalcoholic steatohepatitis or alcoholic cirrhosis) at all stages of the disease that are age greater than or equal to 18 years or less than or equal to 90 years. Treatment can be surgery or therapy. The following check list will be used to verify eligibility of a case subject.

ELIGIBILITY CRITERIA- HCC CANCER CASES

  1. Diagnosed with primary liver cancer (HCC) within the last two years
  2. Physician diagnosis based on AFP and ultrasound/imaging or Pathological diagnosis of primary liver cancer made at the local hospital pathology department
  3. Resides in Maryland or surrounding states
  4. Has a residential working phone within his/her home (*The reason for a participant having a residential working phone is that the matching population controls are selected through the Department of Motor Vehicles records and must have a residential telephone number to be selected as part of the random sample.)
  5. Age is greater than or equal to 18 years and less than or equal to 90 years
  6. A non-objection statement by the physician from the hospital where the patient was identified, or listed as the treating physician by the tumor registry or surgical pathology report, to contact the patient is obtained
  7. Is not currently residing in an institution, such as a prison, nursing home, or shelter
  8. Is not a severely ill patient in the intensive care unit
  9. Is able to give informed consent
  10. Is physically and mentally capable of performing the interview
  11. Must understand English well enough to be interviewed
  12. Has never been interviewed as a control for this study
  13. Subject provides informed consent and signs form.

ELIGIBITY CRITERIA HIGH RISK NON-CANCER CASES

  1. Has been diagnosed with chronic Hepatitis B or C, NASH or alcoholic liver disease with chronicity present at least for a 6 month period
  2. Resides in Maryland or surrounding states
  3. Has a residential working phone within his/her home
  4. Age greater than or equal to 18 years and less than or equal to 90 years
  5. A non-objection statement by the physician from the hospital where the patient was identified or is being treated or by the surgical pathology report, to contact the patient is obtained
  6. Is not currently residing in an institution, such as a prison, nursing home, or shelter
  7. Is not a severely ill patient in the intensive care unit
  8. Is able to give informed consent
  9. Is physically and mentally capable of performing the interview
  10. Must understand English well enough to be interviewed
  11. Has never been interviewed as a control for this study
  12. Subject provides informed consent and signs form.

SELECTION OF POPULATION-BASED CONTROLS

Population-based controls will be identified through the Motor Vehicle Administration (MVA), and matched on age (year of birth), race, gender and geography to cases. We sample controls in proportion to the population size of their county of residence. Recruitment of controls will start concurrently with case accrual, using the age, race and gender frequency distribution of cancer patients in previous years. The sampling frame is continually updated as we accrue information on the case distribution of age, race and gender. We will exclude controls that do not have a listed home phone number. The following check list will be used to verify eligibility of a control subject.

ELIGIBILITY CRITERIA - POPULATION-BASED CONTROLS

  1. Resides in Baltimore City, Anne Arundel, Baltimore, Caroline, Carroll, Cecil, Dorchester, Harford, Howard, Kent, Queen Anne s, Somerset, Talbot, Wicomica and Worchester County.
  2. Has a residential working phone within his/her home
  3. Age greater than or equal to 18 years and less than or equal 90 years
  4. Have never had radiation therapy or chemotherapy
  5. Is not currently residing in an institution, such as a prison, nursing home, or shelter
  6. Is physically and mentally capable of performing the interview
  7. Must understand English well enough to be interviewed
  8. Has never been interviewed as a control for the study
  9. Subject provides informed consent and signs form.

EXCLUSION CRITERIA:

Exclusion Criteria-HCC CANCER CASES

  1. Liver cancer patients who are older than 90 years are excluded because of co-morbidity considerations and the difficulty of matching those cases with population-based controls.
  2. Children and institutionalized patients are excluded from the proposed study. Very few HCC patients at the 3 participating hospitals are younger than 18 years of age and HCC incidence mainly occurs in adults.

Exclusion Criteria-HCC HIGH-RISK NON-CANCER CASES

  1. High Risk Non-Cancer patients who are older than 90 years are excluded because of co-morbidity considerations and the difficulty of matching those cases with population-based controls.
  2. Children and institutionalized patients are excluded from the proposed study. Very few HCC patients at the 3 participating hospitals are younger than 18 years of age and HCC incidence mainly occurs in adults. High-Risk Non-Cancer cases who are younger than 18 years are excluded due to the need of matching with HCC cases and population controls.

Exclusion Criteria-POPULATION BASED CONTROLS

  1. Population based controls who are older than 90 years are excluded because of co-morbidity considerations and the difficulty of matching with HCC cases and high risk non-cancer cases.
  2. Population controls who are younger than 18 years and are institutionalized are excluded due to the need of matching with HCC cases and high-risk non-cancer cases.
  3. Population controls with prior cancer with the exception of non-melanomic skin cancer (squamous or basal cell).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00913757

Contacts
Contact: Dean L. Mann, M.D. (410) 328-5512 dmann001@umaryland.edu
Contact: Xin Wang, M.D. (301) 496-2099 xw3u@nih.gov

Locations
United States, Maryland
University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States
Veterans Affairs Medical Center Recruiting
Baltimore, Maryland, United States
Sponsors and Collaborators
Investigators
Principal Investigator: Xin Wang, M.D. National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT00913757     History of Changes
Obsolete Identifiers: NCT00980564
Other Study ID Numbers: 999909149, 09-C-N149
Study First Received: June 3, 2009
Last Updated: October 11, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Hepatocellular Carcinoma
Liver Cancer
Chronic Liver Disease
Genome Wide Association Study
Gene Expression Profiling

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Carcinoma
Carcinoma, Hepatocellular
Hepatitis
Hepatitis A
Hepatitis, Chronic
Liver Cirrhosis
Liver Cirrhosis, Alcoholic
Liver Neoplasms
Adenocarcinoma
Alcohol-Induced Disorders
Alcohol-Related Disorders
Chemically-Induced Disorders
Digestive System Diseases
Digestive System Neoplasms
Enterovirus Infections
Hepatitis, Viral, Human
Liver Diseases
Liver Diseases, Alcoholic
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Picornaviridae Infections
RNA Virus Infections
Substance-Related Disorders
Virus Diseases

ClinicalTrials.gov processed this record on October 21, 2014