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Preventing Cervical Cancer in the First Mile of the Cancer Care Continuum

在癌症护理连续体的第一英里预防宫颈癌

基本信息

批准号：
10201847
负责人：
Jenna Lynne Hook Mueller
金额：
$ 24.9万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-08 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10201847
关键词：
Ablation Acute Advanced Development Adverse event Aftercare Animal Model Area Award Caliber Cause of Death Cellulose Cervical Cervix Uteri Cessation of life Clinical Clinical Research Cold Therapy Communities Continuity of Patient Care Devices Disease Distress Electrocoagulation Encapsulated Epithelial Epithelium Ethanol Exocervix Family suidae Formulation Gel Goals Health Services Accessibility Histopathology Hour Human Hysterectomy Injections Intervention Investigational Drugs Lesion Liquid substance Liver neoplasms Malignant - descriptor Malignant Neoplasms Malignant neoplasm of cervix uteri Manuals Methods Modeling Monitor Necrosis Nitrogen Outcome Patients Phase Price Procedures Process Public Health Research Resources Safety Site Specimen Speculums Techniques Testing Time Tissues Total Hysterectomy Toxic effect Translations Treatment Cost Woman Work World Health Organization aqueous base cancer care cervical cancer prevention clinical translation cost design improved in vivo interest low and middle-income countries mechanical properties meetings mortality novel portability pre-clinical preclinical study pressure prevent translation to humans treatment arm treatment strategy tumor tumor ablation

项目摘要

Cervical cancer is the second leading cause of death for women worldwide with 85% of deaths occurring in low- and middle-income countries (LMICs), despite the fact that well-established interventions exist for pre- invasive disease. One of the barriers to cervical cancer prevention is reliable access to treatment. Cryotherapy, which is the current therapy recommended by the World Health Organization (WHO) for treating cervical pre- cancer in LMICs, requires a continuous supply of pressurized liquid nitrogen, which is expensive and difficult to transport, and does not adequately treat advanced lesions. More recently, the thermocoagulator has gained acceptance for ablation of cervical pre-cancer lesions because of its ability to treat both low-grade and high- grade pre-cancers. However, thermocoagulation (while effective) has a price point of $1500 to $3,000, which is inaccessible at the community level. These well-documented shortcomings demonstrate a clear unmet clinical need to develop new treatment strategies to prevent cervical cancer in LMICs. To meet this unmet need, our group has recently developed a novel tumor ablation technique based on ethanol ablation. Ethanol ablation was previously developed as a low-cost treatment for encapsulated, inoperable liver tumors, and involves manual injection of pure ethanol into malignant tissue. Preclinical studies showed that while manual injection of pure ethanol is ineffective in treating epithelial lesions, a novel formulation that combines ethanol with an agent ethyl cellulose substantially improved efficacy and induced complete regression of 7 out of 7 tumors. Ethyl cellulose not only makes ethanol more viscous (which prevents backflow) but also forms a gel in an aqueous medium, which sequesters ethanol in the region of interest. Gel ethanol does not require hard-to-supply consumables and has the potential to be ultra-low-cost and highly portable. The goal of this proposal is to optimize the injection procedure and delivery mechanism to treat pre-invasive lesions of the cervix as an alternative to thermocoagulation. To achieve this, the aims are to: 1) establish a method to optimize gel ethanol delivery, 2) assess the safety and efficacy of optimized delivery in a large animal model, and 3) conduct an initial assessment of an optimized delivery procedure in the human cervix. The K99 phase includes the optimization of the gel ethanol injection procedure in Aim 1 and the preclinical studies proposed in Aim 2, which will lay the groundwork for a pre-investigational new drug (IND) meeting and transitioning to clinical studies. The R00 phase includes the optimization of a gel ethanol delivery mechanism and translation to human studies. An independent clinical study is proposed for the R00 portion of the award. These aims will lead to an optimized gel ethanol delivery procedure whose safety and efficacy are validated in a large animal model with an initial assessment in human cervices, which will lay the groundwork for clinical translation.

宫颈癌是全世界妇女死亡的第二大原因，85%的死亡发生在