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Inter-SPORE Prostate Biomarkers Study and NBN Pilot
Protocol Summary
Introduction
Study Objectives
Principal Investigator:
Bruce J. Trock, Ph.D.
Johns Hopkins School of Medicine
Participating Institutions:
Baylor University
Dana Farber Cancer Institute
Fred Hutchinson Cancer Center/Pacific Northwest SPORE
Johns Hopkins School of Medicine
Mayo Clinic
Memorial Sloan Kettering Cancer Center
Northwestern University
University of Michigan
University of California, San Francisco
University of California, Los Angeles
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Protocol Summary
This project has four primary objectives:
- To conduct a multi-institutional Inter-Prostate SPORE prospective validation study of five promising prognostic biomarkers. These biomarkers were selected following a meta-analysis of potential prognostic biomarkers that identified those that currently had the most compelling retrospective data to suggest an independent prognostic effect.
- To conduct limited, focused retrospective studies of three biomarkers deemed highly promising but currently requiring additional evidence of prognostic utility before prospective validation is justified.
- To establish a resource of well-characterized tissue and serum samples linked to clinical and epidemiological data for future biomarker discovery and validation.
- To serve as a "real world" pilot test for critical elements of the National Biospecimen Network (NBN) by evaluating the performance of the following elements of the IPBS: (a) standardized sample handling and processing protocols, (b) standardized sample annotation and clinical annotation protocols, (c) standardized specimen storage and disbursal protocols, (d) governance and prioritization of access to specimens in the biospecimen resource (e) bioinformatics infrastructure.
Introduction
Despite the large numbers of studies that have evaluated molecular prognostic biomarkers over the years, no new biomarkers are regularly used in prostate cancer clinical decision making. Indeed, this is the case for most solid tumors. A major reason for the lack of translation of these biomarkers to the clinic is that results are often inconsistent, and are largely derived from relatively small retrospective studies that use convenience samples, lack standardized methods, often omit multivariable control of established prognostic factors, and may come from only a single institution or research team. In particular, variability in methods of processing tissue samples can lead to divergent results between studies. To facilitate validation of promising biomarker(s) and increase the likelihood of their ultimate widespread clinical application it is important to conduct multi-institutional prospective studies with consistent, standardized protocols. This permits (1) targeting of the patient population of greatest clinical interest, (2) enrollment of a representative sample of sufficient statistical power, (3) collection of all requisite data in a uniform fashion, and (4) performance of biomarker assays in a standardized fashion with appropriate quality control and blinded assessment. The proposed study will achieve these goals and provide a platform for future studies of biomarker validation.
Study Objectives
This 5 year study will prospectively enroll (over a 2 year period) men with newly diagnosed prostate cancer with a moderately high risk of recurrence, who elect to undergo either radical prostatectomy (700 men) or radiation therapy (700 men). The primary clinical endpoint will be PSA recurrence. PSA doubling time and response to metastatic treatment will be secondary endpoints. The study will consider biomarkers measurable in needle biopsy specimens, tissue from prostatectomy specimens, and serum. All specimens will be obtained prior to any form of adjuvant treatment.
In order to achieve the aims of the IPBS, this project will create a formal mechanism for prospectively collecting and storing human tissues linked to clinical and epidemiologic data, with HIPAA compliant consent procedures. This dynamic resource will not only support testing of the proposed markers but will also facilitate the discovery and testing of new markers through additional study components utilizing expression array and array CGH analyses. This resource will be associated with a centralized Pathology Core to ensure consistent handling and processing of samples and to conduct the microarray analyses. The Core will provide every investigator conducting biomarker assays with a set of specimens from each patient enrolled in the study. Since patients are enrolled at multiple SPORE sites it would be impractical and highly error prone to have each SPORE site attempt to allocate specimens for its own biomarker analysis and then send remaining tissue slides or fluid to the other SPOREs. Instead, each SPORE site will send specimens to the Pathology Core. The samples will be apportioned for each investigator, assigned a new ID number that blinds the receiving investigator to the SPORE site that enrolled the patient, and sent along with de-identified data to each investigator. This Core will also be responsible for coordinating quality control procedures with each of the investigators.
The goal of the NBN is, on a larger scale, analogous to that of the IPBS, i.e. to support rigorous biomarker research with a major emphasis on control of pre-analytical error. This will require considerable efforts to achieve, wherever possible, standardized protocols for sample collection, sample processing, and sample storage. In a dispersed network like the NBN or even the SPOREs, differing clinical and institutional imperatives are a barrier to complete standardization. Thus, in evaluating the real-world setting of the IPBS and maintaining detailed sample annotation, it will be possible to document critical sources of variability, and evaluate the influence of protocol variables on bioassay results. This will not only inform the interpretation of biomarker data, but may help to identify protocols that should be considered as "best practices."
It should be emphasized that a necessary component of this project will be a bioinformatics infrastructure that links the participating SPOREs and allows communication and exchange of data and samples. This has been a goal for inter-SPORE collaboration since the beginning of the SPORE program. Thus, in the course of conducting the IPBS and pilot-testing NBN critical elements, this project will also provide the SPOREs with a long-sought bioinformatics network that will be scalable to facilitate migration to other organ sites.
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