SBIR-STTR Award

We are developing an improved clinical method to treat patients with malignant pleural effusions. A pleural effusion is an abnormal build-up of fluid in the pleural cavity, the fluid space that surrounds the lungs. These malignant pleural effusions (MPE) occur in 150,00-175,000 patients in the US each year, affecting between 7 to 15% of all cancer patients. Management of a MPE is palliative and typically involves drainage of the accumulated fluid followed by either placement of a long term drainage catheter or a procedure to induce obliteration of the potential pleural space through inflammation and adhesion formation termed pleurodesis. The simplest and least invasive procedure is tube thoracostomy with chemical pleurodesis. The main problem with the current techniques is its frequent clinical secondary failure rate due to the inefficient and non-uniform distribution of the sclerosing agent. Our overarching Phase I Specific Aims are focused on the development of an improved clinical approach to administering the sclerosing agent to overcome the problems with the current clinically practiced methods. Specific aims of this proposal are: Specific Aim 1: Develop three optimized talc formulations with the newly-developed biocompatible hydrogel, TRI-726 and demonstrate a uniform dispensing distribution of the resulting foaming Hydrogel + talc formulation in combination with and without a propellant. Specific Aim 2: Demonstrate feasibility of the approach in an animal model of pleurodesis. Impact and Future Studies: By providing a novel improved procedure to administer a sclerosing agent we expect to provide a more uniform dispersion of the agent with prolonged contact time that avoids reagent pooling that results in poor efficacy. This approach is expected to significantly impact the current clinical standard of care and result in markedly improved clinical outcomes with a simple, minimally invasive procedure.

Public Health Relevance Statement:
Project Narrative We are developing an improved clinical method to treat patients with malignant pleural effusions, a condition that occur in 150,00-175,000 patients in the US each year, affecting between 7 to 15% of all cancer patients. Management of a MPE is palliative and the main problem with the current techniques is its frequent clinical secondary failure rate due to the inefficient and non-uniform distribution of the sclerosing agent. Our focus is on the development of an improved clinical approach to administering the sclerosing agent to overcome the problems with the current clinically practiced methods. This approach is expected to significantly impact the current clinical standard of care and result in markedly improved clinical outcomes with a simple, minimally invasive procedure.

Project Terms:
Adhesions; aerosolized; Affect; Analgesics; Animal Model; base; biomaterial compatibility; Breathing; Cancer Patient; Catheters; Chemicals; Chest Tubes; Clinical; clinical practice; Complication; Control Groups; Development; Drainage procedure; Drug Delivery Systems; Dyspnea; Effectiveness; Exhibits; Failure; fibrogenesis; Formulation; Future; Gel; Hydrogels; improved; In Situ; Inflammation; Inflammatory; internal control; irritation; Left; Liquid substance; Local anesthesia; Local Therapy; Lung; Malignant Neoplasms; Malignant Pleural Effusion; Methods; minimally invasive; Modeling; Morbidity - disease rate; novel; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; palliative; Palliative Care; Parietal; Patients; Pharmaceutical Preparations; Phase; Pleura; Pleural; Pleural cavity; Pleural effusion disorder; Pleurodesis; Polymers; prevent; Procedures; propellant; Property; Quality of life; Reaction; Reagent; Saline; Sclerosing Agents; sedative; Shortness of Breath; Side; standard of care; Syringes; Talc; Techniques; Thoracostomy; Time; Tube; Visceral

We are developing an improved clinical method to treat patients with malignant pleural effusions (MPE), a serious condition that occurs in 150,00-175,000 patients in the US each year, affecting between 7 to 15% of all cancer patients. MPE results in an excessive accumulation of liquid in the pleural cavity, frequently leaving the patient to suffer from shortness of breath and overall poor quality of life in their remaining months. Management of MPE is palliative and the main problem with the current techniques such as pleurodesis is its frequent clinical failure rate due to the inefficient and non-uniform distribution of the sclerosing agent. Currently, there is no standardization and consensus within the medical community on the optimal delivery technique for a sclerosing agent because of the tradeoffs and variability in patient satisfaction, efficacy, costs, and complexities. This has led to little progress and many of the current clinical gold standard techniques have not evolved in over 80 years. Our focus is on the development of an improved clinical approach to administering a sclerosing agent, which will overcome the problems with those currently practiced methods. In Phase I feasibility studies, we developed and evaluated several foam formulations and have selected a lead candidate. We fully characterized the lead, demonstrating its desired adhesiveness, gelation and reverse thermo-sensitive properties as well as its efficacy in an animal model. These results enable us to proceed with optimization of the lead in parallel with finalizing the design of our proprietary delivery system in this proposed Phase II project. The objectives of the study will be to generate a fully functional prototype with complete manufacturing specifications and user guides, and to also evaluate the safety and efficacy of the lead formulation during biocompatibility studies conducted under GLP conditions, in order to prepare a data package for an IND application to the Food and Drug Administration. Once successfully completed, these Phase II results will prepare us to initiate first-in-human clinical trials where we will test the functional prototype of our combination drug device in collaboration with several prestigious clinical partners who are an important part of this Phase II team. Our multidisciplinary team lead by an experienced cardiothoracic surgeon, has the demonstrated requisite expertise ranging from innovating in chemical and mechanical engineering, navigating the FDA regulatory pathway for combination products, successfully commercializing pharmaceutical and medical device products, to successfully exiting companies. The funding sought through the SBIR Phase II program will be critical to enable us to achieve important R&D milestones that we will further leverage for attracting outside sources of capital from investors, many who are already expressing interest. Our novel approach is expected to significantly impact the current clinical standard of care and result in markedly improved clinical patient outcomes with a simple, minimally invasive procedure.

Public Health Relevance Statement:
Project Narrative. Malignant pleural effusion (MPE) is a complication of late stage cancer, affecting 7 to 15% of all cancer patients and current palliative treatment techniques have high failure rates. To address the main problem with current clinical practice that results in treatment failure due to poor drug delivery and non-uniform distribution of the sclerosing agent, we are developing a novel clinical method of administering it with a new hydrogel foam delivery system. Our approach is expected to significantly impact the current clinical standard of care and markedly improve the clinical outcomes with a simple, minimally invasive procedure.

NIH Spending Category:
Bioengineering; Biotechnology; Cancer

Project Terms:
Address; Adhesions; Adhesiveness; Advanced Malignant Neoplasm; Affect; Animal Model; Animal Testing; biomaterial compatibility; body system; Cancer Patient; Capital; Characteristics; Chemicals; Chemistry; Chest; Chest Tubes; Chest wall structure; Client satisfaction; Clinical; clinical application; clinical practice; Clinical Research; Clinical Trials; clinically relevant; Collaborations; Communities; Complication; Consensus; Control Groups; cost; Data; design; Development; Devices; disabling symptom; Drainage procedure; Drug Combinations; Drug Delivery Systems; Effectiveness; efficacy testing; Engineering; Ensure; Evaluation; experience; Failure; FDA approved; Feasibility Studies; first-in-human; Formulation; Funding; Gamma Rays; Gel; Generations; Goals; Gold; Grant; Guidelines; Histopathology; Human; Hydrogels; implantation; improved; In Vitro; innovation; Instruction; interest; Intervention; Lead; lead candidate; lead optimization; Liquid substance; Lung; Malignant Neoplasms; Malignant Pleural Effusion; Measures; Mechanics; Medical; Medical Device; Methods; minimally invasive; Modeling; multidisciplinary; novel; novel strategies; Oryctolagus cuniculus; Outcome; palliative; Palliative Care; Pamphlets; Parietal pleura; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; phase 1 study; Pleural cavity; Pleurodesis; pre-clinical; Preparation; pressure; prevent; Procedures; Process; process optimization; programs; propellant; Property; Protocols documentation; prototype; Quality of life; reduce symptoms; Regulatory Pathway; Reproducibility; research and development; Research Personnel; Safety; safety assessment; Saline; Sclerosing Agents; Selection Criteria; Shortness of Breath; Site; Small Business Innovation Research Grant; Source; stability testing; standard of care; Standardization; Sterility; Sterilization; Surgeon; System; Talc; Techniques; Temperature; Testing; Tissues; Toxicology; Training; Transition Temperature; Treatment Failure; United States Food and Drug Administration; usability; Visceral pleura; Viscosity