NeoTherma Oncology (NTO/www.neothermaoncology.com) has developed a novel non-invasive medical device that delivers mild hyperthermia (HT) loco-regionally as adjuvant therapy to standard of care treatment of abdominal deep-seated tumors. The VectRx device, designated "Breakthrough" by the FDA, has demonstrated its ability to safely heat abdominal organs (pancreas, liver, kidney, spleen) in pre-clinical studies in healthy swine. FDA approved an investigational device exemption for VectRx on the basis of these data and the lack of a validated large animal tumor model for pancreatic cancer. NTO has initiated a First in Human early feasibility study (EFS) study at the University of Maryland Medical Center to collect initial safety and performance data in pancreatic cancer patients. In parallel to the EFS, NTO will collaborate with University of Colorado-Boulder researchers who have developed a microwave thermometer (MT) that could be utilized to non-invasively measure temperatures in deep tissue. This development is based on the ability to detect the black body radiation proportional to temperature that is emitted at different tissue depths from skin to deep organ. Successful integration of the MTs will effectively improve the clinical utility of VectRx. This will address challenges posed by the limited availability, access, high cost, logistical concerns and reliance on specialized personnel, as is the case with magnetic resonance thermometry. A series of MTs and a radiometer will be designed, fabricated, and integrated into VectRx with potential VectRx coil adjustments to 1) achieve compatible designs of active and passive MTs with operation within VectRx (on and off); 2) manage any potential heating of the MTs, coil detuning, E-field and H-field pattern integrity during VectRx operation. Following co-development and optimization, the MTs's performance will be established in a hepatocellular carcinoma (HCC) Oncopig model with an accuracy goal of 1.5°C. HCC is a disease with low survival rates and only a small fraction (15%) of newly diagnosed patients are eligible for curative treatments due to late diagnosis. The model is relevant to NTO's indication pipeline of deep-seated abdominal tumors, and NTO has previously completed installation of the VectRx device and performed preliminary work in 3 HCC Oncopigs with the veterinary team at the University of Illinois to optimize ultrasound- guided surgical placement of fiberoptic probes that will be used to correlate temperatures measured by the MTs. Despite the known benefits of mild HT, it has not been widely adopted in the US because of the technical limitations of current technologies to address deep, hard to heat tumors and the lack of thermometry. In this Phase I project, we will demonstrate that these critical deficiencies can be overcome through integration of novel microwave-based temperature techniques with VectRx, providing an innovative demonstration of advanced temperature monitoring of HT in deep tissue in a large animal tumor model.
Public Health Relevance Statement: Project Narrative Clinical trials show that hyperthermia sensitizes tumors to standard chemotherapy and radiation treatments and improves patient outcomes, but adoption in the US has lagged due to inadequate devices and the inability to measure tissue temperature to ensure safety and effectiveness. In this proposal, NTO and the University of Colorado-Boulder will co-develop and validate in a pig model a microwave thermometer customized for operation with VectRx, a device NeoTherma Oncology (NTO) has developed to safely heat deep solid tumors. Success in this study will provide NTO with a practical, low-cost non-invasive pathway to measure temperature in deep tissue with microwave thermometers.
Project Terms: Abdominal; Abdomen; Adoption; Affect; Animals; Chicago; Cities; Clinical Trials; Colorado; Diagnosis; Disease; Disorder; Electronics; electronic; electronic device; Elements; Eligibility Determination; Eligibility; Protocol Screening; Environment; Fat necrosis; Steatonecrosis; Feasibility Studies; Feedback; Fiber Optics; Future; Goals; Heating; Primary carcinoma of the liver cells; Hepatocarcinoma; Hepatocellular Carcinoma; Hepatocellular cancer; Hepatoma; Liver Cells Carcinoma; liver carcinoma; Human; Modern Man; Illinois; Kansas; Kidney; Kidney Urinary System; renal; Liver; hepatic body system; hepatic organ system; Liver neoplasms; Hepatic Neoplasms; hepatic neoplasia; hepatic neoplasm; hepatic tumor; liver tumor; Longitudinal Studies; long-term study; longitudinal outcome studies; longterm study; Magnetic Resonance Imaging; MR Imaging; MR Tomography; MRI; MRIs; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; NMR Imaging; NMR Tomography; Nuclear Magnetic Resonance Imaging; Zeugmatography; Marketing; Maryland; Medical Device; microwave electromagnetic radiation; Microwave Electromagnetic; Microwaves; microwave radiation; Pancreas; Pancreatic; Patients; Radiation-Sensitizing Agents; Radiation Sensitizers; Radiation-Sensitizing Drugs; Radiosensitizing Agents; Radiosensitizing Drugs; Radiotherapy sensitizer; radiosensitizer; Radiation therapy; Radiotherapeutics; Radiotherapy; radiation treatment; treatment with radiation; Research Personnel; Investigators; Researchers; Safety; Spleen; Spleen Reticuloendothelial System; Survival Rate; Family suidae; Pigs; Suidae; Swine; porcine; suid; Technology; Temperature; Testing; Thermometers; Time; Tissues; Body Tissues; Translations; translation; United States; Universities; Work; Measures; Drug Delivery; Drug Delivery Systems; Mediating; Organ; Thermometry; sensor; improved; Acute; Clinical; Phase; Series; Ensure; Measurement; Oncology Cancer; Oncology; Solid Tumor; Solid Neoplasm; Collaborations; tool; Malignant neoplasm of pancreas; Malignant Pancreatic Neoplasm; Pancreas Cancer; Pancreatic Cancer; pancreatic malignancy; Adopted; Frequencies; Pattern; Techniques; System; Location; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Services; Medical center; biomaterial compatibility; biocompatibility; dielectric property; Performance; success; Transgenic Organisms; transgenic; Adjuvant Therapy; adjuvant treatment; Structure; novel; Devices; Human Resources; Manpower; personnel; Reporting; Radiation; Modeling; Magnetic Resonance; Skin; Effectiveness; Address; Data; Resolution; resolutions; Newly Diagnosed; Patient-Focused Outcomes; Patient outcome; Patient-Centered Outcomes; patient oriented outcomes; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Monitor; Characteristics; Modification; Development; developmental; Clinical Services; Pathway interactions; pathway; preclinical study; pre-clinical study; cost; designing; design; innovate; innovative; innovation; Implant; optical fiber; prototype; tumor; FDA approved; standard of care; risk mitigation; operations; operation; Hyperthermia; Geometry; radiofrequency hyperthermia; invention; curative intervention; curative therapeutic; curative therapy; curative treatments; experiment; experimental research; experiments; experimental study; perfusion imaging; first in man; first-in-human; pancreatic tumor model; pancreatic cancer model; patients with pancreatic cancer; pancreatic cancer patients; Chemotherapy and Radiation; chemo/radiation therapy; chemotherapy and radiotherapy; radiation or chemotherapy; Chemotherapy and/or radiation; in silico; skin burn; pig model; piglet model; swine model; porcine model; Oncopig; ultrasound
