Description:
Fast-Track proposals will be accepted.
Direct-to-Phase II proposals will NOT be accepted.
Number of anticipated awards: 1-3 Budget (total costs, per award):
Phase I: up to $400,000 for up to 9 months Phase II: up to $2,000,000 for up to 2 years
PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.
Summary
This solicitation calls for the development of electronic devices to replace current radiation sources for use in the clinic allowing for implementation using existing high dose rate (HDR) applicators. The goal is to leverage the full, existing radiation therapy infrastructure (training and applicator set investment) to provide radioactive source-free (e.g., iridium) brachytherapy. Submissions will be responsive if the proposed electronic brachytherapy sources are substitutable for radioactive sources currently in use in the clinic via use with unmodified commercial applicator sets.
Brachytherapy, in surface, intracavitary and interstitial forms, using small radioactive sources is a critical component of global radiation therapy and is a mainstay in the cure for diseases like cervical cancer, sarcoma, and recurrent cancer. It is used in both adult and pediatric patient populations. The methods used are proven, affordable, and offer unique advantages to patients in terms of dosimetry - even relative to particle therapy. However, the permanent radioactivity of sources creates issues and costs related to safety and security that electronic devices would not present. Turning an electronic device off causes the radiation emission to cease. In addition, electronic sources may present unique, new advantages for dosimetric control of radiation.
To be responsive to this FOA submissions must develop and test devices that can be employed using existing brachytherapy infrastructure. In this context, the proposed devices must be compatible with the current applicators available on the market. Applicator set examples can have paths with small radii of curvature and include ring and ovoid sets and tandem and ovoid sets for cervical cancer, catheters for prostate cancer, head and neck cancer and sarcoma, and even devices allowing ocular, skin, and nasopharyngeal deployment. Use of these devices is critical so as to take advantage of infrastructure and established safety and efficacy data.
Project Goals
This contract solicitation seeks to stimulate research, development, and commercialization of innovative devices to replace and enhance the radiation space currently occupied by radioactive sources in brachytherapy. To apply for this topic, offerors should:
• Develop an appropriate electronic device and control system to allow integration into the clinic.
• Measure and define the radiation characteristics of the device: output spectrum, stability, dose rates possible, and similar capacities for modulation of dose.
• Validate that the planned (final) device will be deployed in a clinical setting using existing brachytherapy devices (applicator sets). Devices must be able to move around curves and cannot depend on waveguides.
Activities not responsive to announcement:
1. Approaches requiring new infrastructure (patient applicator modifications, treatment planning system standards changes, imaging protocol modifications) are not appropriate for this solicitation.
2. Penetration of radiation in tissue must be equal to or greater than 1 cm and energy of the beam produced must be equal or greater to 250 kV. Devices unable to achieve these energy output constraints or greater will be considered non- responsive.
Phase I Activities and Deliverables:
• Establishment of a project team that includes necessary expertise in: electronic devices capable of delivering radiation that are small in size (physics/engineering); software development for device control and operation, user- centered design for interface design, radiation/clinical oncology delivery and processes, medical devices regulations and manufacturing process expertise. Medical knowledge of brachytherapy practice and delivery is required.
• Develop a fully functional prototype that can be used with existing HDR medical devices (tandems, rings, sarcoma catheters, partial breast devices).
o Confirm (documentation to be reported) that the device delivers dose at an energy and dose rate required of this announcement (penetration of radiation in tissue must be equal to or greater than 1 cm and energy of the beam produced must be equal or greater to 250 kV).
o Demonstrate device stability in a model (phantom) of clinical use (motion, temperature, normal handling, dose rate, energy, with repetition). The device needs to be able to tolerate a 30 cm drop onto a solid surface without measurable change to the radiation delivered by the device.
o Develop standard operating procedures to confirm dose delivery/validation of device function and stability. These must allow NIST traceability to be achieved in phase II.
• Perform in vitro efficacy studies in relevant cancer cell line(s) with normal tissue and standard brachytherapy source device controls.
• Develop user documentation for use of the device.
• Document a telephone call(s) and/or meeting(s) with the FDA discussing the process to achieve an IND and related approvals.
Phase II Activities and Deliverables:
• Develop a device/technology/process to scale up manufacture and calibration of devices centrally so that once produced and sold they are easy to deploy and utilize – test this via making multiple devices that may be calibrated to within 5% dose delivery of each other or better (ideally within 1%).
• Refinement process development for construction of final product by
o Data for the successful scale-up of production of device
o Data documenting the completion of process analytics for production and calibration, including demonstrating the ability to be calibrated in a stable fashion to NIST standards at the factory and in the field,
o Demonstrating the formal, finalized process to allow general production unit’s dosimetric verification
o Documentation demonstrating the completion of safety interfaces and procedures for clinical implementation
• Demonstrate the ability to use a commercial and/or in-house robust and standards-based treatment planning system (TPS) with this device.
o Treatment plans should be able to be taken from the TPS and put into the delivery system so as to control the “delivery” of the plan to a patient in standard fashion.
o If an in-house system is developed, appropriate FDA approval processes must take place and demonstration that this TPS can properly interact with at least two leading TPS systems must be documented (plan import and export).
o Published interface data and standards compliance for all interfaces so that a commercial TPS vendor “could” provide services to the device with their TPS.
• Demonstration of continued, close communication with the FDA in years one and two to initiate the trials and processes needed to achieve full IND approval. Trials should be at least in the process of IRB review.
• In the second year of the contract, provide the program and contract officers with a letter(s) of commercial commitment.
