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250 Biopsy Instruments and Devices that Preserve Molecular Profiles in Tumors

Number of anticipated awards: 4
(Fast-Track proposals will be accepted.)
Budget (total costs): Phase I: $250,000;
Phase II: $2,000,000
Project duration: Phase I: 6-12 months;
Phase II: 2 years

The deadline for receipt of all contract proposals submitted in response to this solicitation is: 5:00 p.m. Eastern Standard Time Monday, November 5, 2007

Molecular medicine holds much promise for advancing cancer diagnosis and treatment, if biomarkers, molecular targets and drug effects on these targets can be accurately assessed in tumor nodules in the viscera. The amount and function of molecular drug targets within signal transduction pathways are often regulated by rapid enzymatic reactions in response to physiological stimuli. Biopsies play a central role in assessing biomarkers and molecular targets in solid tumors, but conventional practices and medications used by surgeons and interventional radiologists necessarily perturb the tumor environment and thereby induce extraneous and confounding molecular responses to tissue trauma, vascular changes, hypoxia, anesthetics, etc. Expeditious processing of the biopsy specimen using snap freezing or rapid fixation are ineffective for preventing many rapid enzymatic modifications, because time frames of biopsy procedures are much longer than that of the enzymatic reactions. Thus, there is a need to develop clinical devices, instruments and approaches suitable for clinical practice that stabilize molecular profiles in visceral tumor lesions during the procedure, and prevent molecular response to the procedure. The diagnostics market includes devices for needle cryobiopsy of breast lesions that freeze the tissue in situ before sampling, but the needle size is too large for percutaneous image-guided biopsy of visceral sites. Although unlikely to improve routine diagnostic biopsies, innovative approaches for tumor biopsy that preserve the molecular profile will create an entirely new diagnostic area and market in molecular therapeutics, which will not only facilitate pharmacodynamic assessment of targeted therapeutics but also enable individualized molecular therapy of solid tumors based on accurate information about signal transduction pathways, molecular drug targets and biomarkers.

Project goals:

The short-term goal of the project is the identification of technical strategies with potential for stabilizing the molecular profile of cancerous lesions in visceral tissue sites during clinical biopsy procedures. The long-term goals of the project are the design and development of operational prototype instruments/devices required to practice the innovative biopsy approach; the demonstration of the operational success of the innovative approach when applied to visceral lesions of solid tumors in model systems; and the evaluation of the potential superiority of the innovative biopsy approach over conventional surgical and radiological procedures for assessing highly dynamic molecular profiles that are associated with a high degree of instability during conventional biopsy procedures. The project scope includes advancements in biopsy technologies and approaches from any medical discipline performing biopsy procedures (surgery, radiology, dermatology, etc.) that improve the fidelity of molecular assessment of visceral tumor lesions. Reaching these goals on the basis of experimental evidence will mark a major advance in the ability to accurately assess the molecular profile of solid tumor lesions of the viscera and the functional status of their molecular targets during early clinical trials of experimental therapeutics. If successful, this project will improve the accuracy of biomarker assessment for diagnosis and prognosis and the information available about the pharmacodynamics and molecular efficacy of targeted drug therapy.

Phase I activities and expected deliverables:

• Identify a technical strategy for preventing changes in molecular status during solid tumor biopsy and articulate its rationale and critical principles of operation.
• Demonstrate the feasibility of achieving the critical principles of the innovative biopsy procedure during biopsy of solid tumor lesions in visceral tissue.
• Demonstrate that the innovative biopsy procedure stabilizes a biochemical process or reaction, or a functional molecular status, that is unstable during conventional surgical or needle biopsy procedures.
• Provide a description of the technical strategy underlying the innovative biopsy approach, the critical operating principles and the experimental design for testing if feasibility has been achieved.
• Provide a summary report of the results proving the feasibility of the innovative biopsy approach in tumor lesions of the viscera.
• Produce histochemical, biomarker, and/or other pharmacodynamic data that demonstrate that the innovative biopsy approach stabilizes a biochemical or molecular endpoint that is unstable during conventional biopsy procedures.

Phase II activities and expected deliverables:

• Design, build and test any innovative biopsy instrument/device required for the new biopsy procedure.
• Develop and validate necessary assays for assessing molecular preservation of at least three biochemical pathways/endpoints that will be useful indicators of molecular stability or instability in solid tumor biopsies from visceral tissue, one of which is suitable to be a general quality control indicator of molecular stabilization in clinical specimens and another of which is a molecular drug target.
• After obtaining appropriate IACUC approval, design and conduct comparative studies of the innovative biopsy approach, conventional surgical biopsy and conventional needle biopsy of visceral lesions of a solid tumor model in animals, using validated assays for at least three biochemical pathways/endpoints , including the quality control indicator and the molecular drug target.
• After obtaining appropriate regulatory approval, design, conduct and use the validated assay(s) in a proof-of-concept clinical trial in solid tumor patients that will test if the innovative biopsy approach is capable of stabilizing at least the quality control indicator of molecular stabilization in biopsies of visceral disease.
• Produce a prototype device or instrument that can be used to obtain molecularly preserved biopsies of solid tumors in visceral organs of large animal models such as canine models.
• Provide written instructions for the operation of any prototype biopsy device or instrument and the procedure for performing the innovative biopsy with quality control measures.
• Provide data confirming that the prototype device/instrument operates within design and performance specifications when used in the veterinary environment.
• Provide results of the comparative study of the innovative and conventional biopsy approaches in the animal model, using the developed and validated assays of at least the three biochemical pathways/endpoints above, one of which must be the quality control indicator and another of which must be a molecular drug target.
• Provide results of the proof-of-concept clinical trial of the innovative biopsy approach applied to visceral solid tumor lesions, including the safety of the innovative procedure, the reliability of the device, and the assay results at least for the quality control indicator of molecular stabilization.

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