Request for Information (RFI): Candidate Biomarkers of Hepatocellular Carcinoma for Validation in a Unique Human Cohort

Notice Number: NOT-CA-10-004

Key Dates
Release Date: October 22, 2009
Response Date: January 5, 2010

Issued by
National Cancer Institute (NCI), (http://www.cancer.gov)

This Request for Information (RFI) is for information and planning purposes only and should not be construed as a solicitation or as an obligation on the part of the Federal Government, the National Institutes of Health (NIH), and/or the National Cancer Institute (NCI). The NCI does not intend to make any awards based on responses to this RFI or to otherwise pay for the preparation of any information submitted or for the Government's use of such information.

Purpose and Objectives

On behalf of the Early Detection Research Network (EDRN) (http://edrn.nci.nih.gov/), the NCI is soliciting input from the scientific community and the general public regarding potential biomarkers for the early detection and diagnosis of hepatocellular carcinoma that can be validated in a large prospective cohort of subjects to be assembled in the near future (see details under Background ). As part of the planning, the NCI asks investigators to propose candidate biomarkers for use in such a study. Suggestions and ideas pertaining to these aspects are also welcome from intramural NIH scientists and consultants working at or with any of the NIH Institutes and Centers.

Background

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide and a rising cause of tumor deaths in the United States. Patients with cirrhosis of the liver form the highest risk group for developing this tumor, and there is an urgent need to develop biomarkers for the early detection of HCC in those patients.

In a study recently completed through the EDRN, promising properties for the diagnosis of HCC were shown by two biomarkers: alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP). Further developmental efforts with these biomarkers are being planned. These efforts (defined as an EDRN phase 3 biomarker study) will actively follow a cohort of cirrhotic patients who are currently being monitored for development of HCC. This study will likely include the examination of AFP and DCP as potential markers (individually and in combination), along with diagnostic ultrasonography.

The subject population to be recruited and followed up affords a unique scientific opportunity to include in the study the prospective examination of other candidate biomarkers prior to the emergence of clinically detectable HCC.

Information Requested

NCI seeks suggestions of novel, promising biomarkers for HCC that might be applicable to the early detection of this cancer. Due to the unique opportunity that the planned study with AFP and DCP presents for preclinical detection of hepatocellular carcinoma, the NCI invites investigators who are not currently associated with the EDRN to propose additional biomarkers that they would like to have studied in this cohort. Biomarkers for early stages of disease are of particular interest. The diagnostic efficacy of any proposed biomarker as determined by a statistically powered case-control study would need to be demonstrated, i.e., the proposed biomarkers must fulfill criteria for the EDRN-defined phase 2 for biomarker validation (as described in JNCI 93(14):1054, 2001, and JNCI 100(20):1432, 2008).

The information gathered will be used for developing an expanded list of potential biomarkers for inclusion in the planned EDRN phase 3 biomarker study. This RFI is thus an opportunity for extramural investigators to promote specific research directions that they consider important for the progress in the area of HCC biomarkers.

Responses

Responses will be accepted through January 5, 2010. Interested persons, groups, and organizations are invited to submit potential biomarkers for the early detection and diagnosis of hepatocellular carcinoma. Responses should be limited to three pages and marked with this RFI identifier NOT-CA-10-004. Responses are preferred in electronic format and can be e-mailed to rinaudoj@mail.nih.gov.

If you are willing to do so, please indicate your primary affiliation/role from the categories listed below:

Academia;
Small Business
Pharmaceutical/Biotechnology Industry;
Federal Government;
State Government;
Healthcare Professional;
Patient Advocacy Group; and
Other (briefly define).

Respondents will receive an email confirmation acknowledging receipt of their response, and will receive individualized feedback.

All individual responses will remain confidential. Any identifiers (e.g., names, institutions, e-mail addresses, etc.) will be removed when responses are compiled. Only the processed, anonymized results will be shared internally with scientific working groups convened by the NCI, as appropriate. Nonetheless, no proprietary information should be submitted.

Inquiries

Inquiries regarding this RFI may be directed to:

Jo Ann Rinaudo, Ph.D.
Cancer Biomarkers Research Group
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, EPN Suite 3148
Bethesda, MD 20892-7362 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301-435-5015
Fax: 301-402-8990
E-mail: rinaudoj@mail.nih.gov