SBIR-STTR Award

This proposal aims to develop a polymer hydrogel strategy that can be used to improve the clinical care of patients receiving brachytherapy for gynecological cancers. The biocompatible hydrogel will form in situ after being injected into the vaginal space, and later removed by instillation of water to soften the hydrogel for easy extraction. This Phase I proposal focuses on optimizing the polymer hydrogel strategy using clinically relevant reagent volumes to deliver a product ready for preclinical and clinical testing. The hydrogel will serve as vaginal packing material during cervical cancer brachytherapy, displacing rectum and bladder, providing attenuation and stabilizing the applicator. Current alternatives include packing the vagina with gauze, which is uncomfortable for patients, subject to errors and provides limited attenuation of radiation dose, and a commercially available balloon system that is expensive and cumbersome to use. The proposed polymer hydrogel strategy would provide a simple, customized strategy for vaginal packing that provides attenuation and consistent imaging properties while improving patient comfort and limiting costs. Our team has also developed a rigid, reusable, 5-channel vaginal cylinder brachytherapy applicator to be used in conjunction with the hydrogel for vaginal cuff brachytherapy. This improves upon existing options for vaginal cuff brachytherapy by providing a customized solution that conforms to patient anatomy and offers more precise radiation delivery while maintaining an efficient workflow. The small business and academic partners will work together to translate this polymer hydrogel prototype to a clinical product that is readily commercializable. The proposed research in phase I will focus on (Aim 1) optimization of the hydrogel for use as vaginal packing for brachytherapy and on (Aim 2) preclinical validation of hydrogel application and removal in the presence of brachytherapy applicators in a model system designed to simulate clinical conditions. The phase I research will provide the foundation for a phase II program focusing on establishing safety and biocompatibility of the hydrogel for human testing and designing clinical trials to evaluate clinical application of the polymer hydrogel product.

Public Health Relevance Statement:
Pelvic brachytherapy is a common treatment for women with gynecologic cancers, particularly cervical cancer and endometrial cancer. Recent advances in image-guided treatment planning and delivery have provided the capacity to deliver highly customized brachytherapy on an outpatient basis, but limitations in the current options for vaginal packing and vaginal cuff brachytherapy methods present obstacles to the delivery of optimal treatments. This project pioneers a new approach for vaginal packing and vaginal brachytherapy using a novel self-expanding polymer hydrogel that will improve accuracy, conformality and patient comfort pelvic brachytherapy. The research team has validated the preliminary concept, and the current proposal aims to develop this approach for clinical use and commercialization.

Project Terms:
Adjuvant Therapy; Air; Anatomy; Anesthesia procedures; Appearance; attenuation; Back; base; biocompatible polymer; Biological Models; biomaterial compatibility; Bladder; Brachytherapy; Businesses; Caliber; catalyst; Clinical; clinical application; clinical care; clinical development; Clinical Trials Design; clinically relevant; commercialization; common treatment; cost; Crowding; Custom; design; Development; Devices; digital; Dose; Endometrial Carcinoma; Ensure; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; ethylene glycol; Excision; flexibility; Foundations; Gel; Gynecologic Brachytherapy; Human; Hydrogels; Hysterectomy; Image; Image Enhancement; image guided; Imagery; imaging properties; Immune response; Immunology procedure; immunoreaction; improved; In Situ; in vivo; Injectable; Injection of therapeutic agent; Inpatients; Malignant Female Reproductive System Neoplasm; Malignant neoplasm of cervix uteri; Methods; Modeling; Modulus; novel; novel strategies; Outpatients; Patient Care; Patients; Pattern; Pelvic Cancer; Pelvis; Performance; Phase; Physicians; Polymers; pre-clinical; Preclinical Testing; Procedures; programs; prototype; Radiation; Radiation therapy; Reaction; Reagent; reconstruction; Rectum; Research; research clinical testing; Safety; Shapes; standard care; Sulfhydryl Compounds; Swelling; System; Techniques; Technology; Testing; Time; Tissues; Translating; treatment planning; Treatment Protocols; uptake; Vagina; Vaginal Ring; Validation; Water; Woman; Work; X-Ray Computed Tomography

This proposal aims to complete preclinical validation and commercialize a novel vaginal packing product based upon a biocompatible polymer hydrogel strategy. The hydrogel will form in situ after being injected into a bag placed within the vaginal cavity during pelvic brachytherapy. The hydrogel packing can then be removed readily after the brachytherapy treatment. This Phase II proposal focuses on preclinical validation of the hydrogel vaginal packing system in vaginal phantoms and cadavers, proof of biocompatibility by an external lab, and clinical trials of vaginal packing during cervical cancer brachytherapy. The hydrogel will serve as vaginal packing material during cervical cancer brachytherapy, displacing rectum and bladder, providing attenuation and stabilizing the applicator. Current alternatives include packing the vagina with gauze, which is uncomfortable for patients, subject to errors and provides limited attenuation of radiation dose, and a commercially available balloon system that is expensive and cumbersome to use. Our innovative polymer hydrogel strategy will provide a simple, customized strategy for vaginal packing that provides attenuation and consistent imaging properties while improving patient comfort and limiting costs. The small business and academic partners will work together to test and commercialize the vaginal packing product for clinical use. The proposed research in phase II will focus on (Aim 1) validation of the hydrogel packing system’s performance in phantoms designed to mimic vaginal cavities, on (Aim 2) evaluation of the biocompatibility of the system and its performance as vaginal packing in soft-curved female cadavers, and on (Aim 3) testing the product in a two-center clinical trial of cervical cancer brachytherapy in 40 human subjects. The phase II research program focuses on generating the evidence needed to support a regulatory application and commercialization of the polymer hydrogel vaginal packing product.

Public Health Relevance Statement:
Pelvic brachytherapy is a common treatment for women with gynecologic cancers, particularly cervical cancer and endometrial cancer. Recent advances in image-guided treatment planning and delivery have provided the capacity to deliver highly customized brachytherapy on an outpatient basis, but limitations in the current options for vaginal packing methods present obstacles to the delivery of optimal treatments. This project validates the preclinical performance and completes a clinical trial in humans for a new, hydrogel-based vaginal packing product for clinical use during image-guided brachytherapy. The product is based upon a novel self-expanding polymer hydrogel technology that will improve the accuracy, conformality and patient comfort of pelvic brachytherapy. The current proposal will lead to validation and commercialization of a new clinical product for pelvic brachytherapy that will improve care for cervical cancer patients.

NIH Spending Category:
Bioengineering; Biomedical Imaging; Cancer; Cervical Cancer; Clinical Research; Clinical Trials and Supportive Activities; Radiation Oncology; Rare Diseases; Vaginal Cancer; Women's Health

Project Terms:
Air; Anatomy; attenuation; base; biocompatible polymer; biomaterial compatibility; Bladder; Body Temperature; Brachytherapy; Businesses; Cadaver; cancer care; Cancer Patient; Caring; Cervical; Characteristics; chemotherapy; Clinical; Clinical Trials; commercialization; common treatment; Conscious Sedation; cost; curative treatments; Custom; design; Development; Dose; Dose-Rate; dosimetry; Endometrial Carcinoma; Evaluation; Excision; experience; External Beam Radiation Therapy; Female; Funding; General Anesthesia; Gynecologic Brachytherapy; Health system; High-Dose Rate Brachytherapy; Human; human subject; Hydrogels; Image; Image Analysis; image guided; imaging properties; imaging system; improved; In Situ; innovation; Interview; Lateral; Magnetic Resonance Imaging; Malignant Female Reproductive System Neoplasm; Malignant neoplasm of cervix uteri; Malignant Neoplasms; Medical; Methods; Modality; Modernization; multidisciplinary; novel; optimal treatments; Oral; Outpatients; Patients; Performance; Phase; Physicians; Polymers; pre-clinical; Preclinical Testing; product development; programs; Radiation; Radiation Dose Unit; rapid technique; Reaction; rectal; Rectum; Reporting; Reproducibility; Research; Sedation procedure; simulation; Site; Speculums; System; Technology; Testing; Thermogenesis; three dimensional treatment planning; Tissues; treatment planning; United States; Universities; uptake; Uterus; Vagina; Validation; Variant; Virginia; Water; Woman; Work