MAJOR ONGOING INITIATIVES

Program for the Assessment of Clinical Cancer Tests

http://www.cancerdiagnosis.nci.nih.gov/assessment/index.htm

Contact:

Sheila E. Taube, Ph.D.
301-496-8639, st29f@nih.gov

Many decisions relating to cancer patient management depend on information derived from clinical laboratory tests. Significant research and development are involved in producing a test that is reliable enough for routine clinical use. CDP launched the Program for the Assessment of Clinical Cancer Tests (PACCT) in 2000 to develop a process for moving the advances in new technologies and new understanding of cancer biology more efficiently and effectively into clinical practice.

Biomarker Development Process

A primary goal of PACCT is to develop more informative laboratory tools to help maximize the impact of cancer treatments. PACCT focuses on developing tests for cancer diagnosis, prognosis, and prediction of response to therapy. PACCT is not a grants program and has not previously focused on building infrastructure. Instead, the program has leveraged other NCI-supported activities to accomplish goals identified by the PACCT Strategy Group. The strategy group is comprised of scientists, drawn from academia as well as the Food and Drug Administration (FDA) and NCI, with expertise in clinical oncology, pathology, basic cancer biology, diagnostics technology and assay development, clinical trials methodology, and statistics.

The strategy group establishes working groups to address critical diagnostic issues in specific tumors as needed. The Breast Cancer Working Group’s efforts led to the Trial Assigning IndividuaLized Options for Treatment (TAILORx), which is assessing the utility of a molecular signature to identify women with early stage breast cancer who can be treated with only hormonal therapy because their risk of recurrence is so low. The signature also identifies those patients who will benefit from the addition of chemotherapy.

The Colon Cancer Working Group is focusing on assay standardization and validation issues. Its goal is to validate tests to determine whether it is possible to identify a subgroup of patients with stage II colon cancer at sufficiently high risk to benefit from adjuvant chemotherapy. As part of these activities, PACCT initiated a study to determine the intra- and interlaboratory reproducibility of assays to determine loss of heterozygosity at chromosome 18, since this assay is being used to stratify patients in a colon cancer clinical trial being led by the Eastern Cooperative Oncology Group (ECOG). The performance of the assay is being evaluated in collaboration with the investigators running the assay for the trial and pathologists from two other cooperative groups. The pathologists also plan to evaluate the specimens from the ECOG trial and two other large adjuvant colon cancer trials to evaluate promising markers to predict response to targeted agents being used in these trials.

Another subcommittee of the PACCT Strategy Group developed criteria for prioritizing studies of essential clinical assays that will be funded through the Coordinating Center for Clinical Trials (CCCT). These criteria were reviewed and approved by NCI’s Clinical Trials Advisory Committee (CTAC).

A subcommittee was also formed to develop a document specifying standards of evidence required to support the inclusion of an assay in a phase III clinical trial. The data justifying the use of the clinical assay must be included in the clinical trial protocol. The document outlining the categories of information to be required was approved by CTAC. Work is now proceeding to specify what information must be included in protocols.

A working group of PACCT organized an NCI/FDA/Industry workshop to consider strategies, challenges, and barriers to the co-development of targeted therapies and predictive assays necessary to optimize the use of the therapies. Three case studies were used to illustrate the challenges and barriers: HER2/trastuzumab, epidermal growth factor receptor (EGFR)/EGFR inhibitors, and a current co-development project presented by industry. Results of the workshop discussions will be presented in a publication addressing the information needed to help make decisions about whether and how to develop the drugs and predictive assays and how best to generate that information.

Over the past several years, the PACCT Strategy Group has identified a series of barriers to the efficient development of clinically useful assays. CDP broadly advertised a Request for Information (RFI) to identify specific needs. Results from the RFI indicated the need for a variety of resources, including specimens, technical assistance, support for statistical expertise, and assay standards. There was also significant interest in having educational materials available to help inform the research community about issues related to clinical assay development. To respond to the identified needs and provide the necessary resources to the research community, CDP is developing a new program called Molecular Diagnostics Evaluation Laboratories, or MoDEL.