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Phase II Clinical trial of GTC in Men on Active Surveillance

GTC 在男性主动监测中的 II 期临床试验

基本信息

批准号：
10673170
负责人：
NAGI B. KUMAR
金额：
$ 59.27万
依托单位：
H. LEE MOFFITT CANCER CTR & RES INST
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10673170
关键词：
5 Alpha-Reductase Inhibitor Adherence Adoption Adverse event Anxiety Apoptosis Biodistribution Biological Biological Availability Biological Markers Biopsy CASP3 gene Cell Survival Cessation of life Characteristics Chemoprevention Chemopreventive Agent Classification Clinical Clinical Trials Conflict (Psychology)Core Biopsy Detection Development Dietary History Disease Disease Progression Dose Double-Blind Method Dutasteride Effectiveness Eligibility Determination Epidemiology Epigallocatechin Gallate Evaluation Experimental Designs Exposure to Finasteride Formulation Future Gene Expression Genes Gleason Grade for Prostate Cancer Green tea Histologic I Kappa B-Alpha In Vitro Incidence Induction of Apoptosis Intervention Kinetics Life Style Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of prostate Measures Mental Depression Molecular Monitor Morbidity - disease rate NF-kappa B Outcome Pathway interactions Patients Pattern Periodicals Phase Phase II Clinical Trials Phase III Clinical Trials Placebos Plasma Prevention strategy Prostate Adenocarcinoma Prostate-Specific Antigen Proteasome Inhibition Quality of life Randomized Recommendation Regulation Reporting Research Risk Risk Reduction Safety Sampling Screening for Prostate Cancer Signal Transduction Standardization Subgroup Testing Therapeutic Intervention Time Tissues Toxic effect Uncertainty Validation Variant cancer chemoprevention carcinogenesis cyclin-dependent kinase inhibitor 1B density design early phase trial epicatechin epicatechin gallate gallocatechol gut microbiome indexing inhibitor lower urinary tract symptoms men metabolomics metatranscriptomics microbiota novel oncotype overexpression overtreatment personalized approach pharmacologic pill post intervention pre-clinical prevent preventive intervention progression risk prostate biopsy prostate cancer cell prostate cancer progression prostate cancer risk prostate carcinogenesis randomized, clinical trials serum PSA tumor

项目摘要

Abstract: The era of screening for prostate cancer (PCa) using serum prostate specific antigen (PSA) has led to an increase in the detection of low-grade prostate cancers that pose little risk of either metastatic spread or death. Additionally, these men may be now exposed to morbidities of over treatment with little or no benefit of cancer-specific survival. Active surveillance (AS) has thus evolved as a recommended management strategy for men with low grade disease, providing the benefit of an individualized approach of carefully monitoring disease progression, sufficient to permit timely therapeutic intervention. However, concerns about under- grading, variations in criteria for AS eligibility, patient reported anxiety, depression, doubts about the possible progression of the disease as well as higher decisional conflict regarding selection of AS, men on AS have been reported to ultimately opt for treatment without any major change in tumor characteristics. On the other hand, men on AS are a subgroup, who are highly motivated and eager to make positive lifestyle changes to further reduce their risk of PCa progression- providing an opportunity for chemoprevention. Chemoprevention strategies with 5-alpha-reductase inhibitors significantly reduced the risk of prostate cancer progression. However their use was also associated with increased detection of high- grade disease, severely limiting their clinical adoption. Currently, there is a paucity of research that systematically examines agents for chemoprevention in men on AS. Green tea catechins (GTC) influence several hallmarks of carcinogenesis, including prostate carcinogenesis, with an acceptable safety profile, making them attractive candidates for PCa chemoprevention. Several epidemiological, in vitro, preclinical and early phase trials completed by our team and others have shown that the GTC are potent inhibitors of PCa carcinogenesis through multiple mechanisms, bioavailable in tissue and plasma, reduces several intermediate biomarkers implicated in PCa progression and without toxicities at these doses. Based on the available evidence, we hypothesize that men with biopsy proven adenocarcinoma of the prostate who meet the criteria for AS, who receive GTC at a dose of 800 mg EGCG per day (vs. placebo) for 24 months, will have a significantly decreased rate of clinical progression. We will test this hypothesis using a rigorous experimental design in a phase II, randomized clinical trial to evaluate the safety, effectiveness and potential mechanism by which GTC modulates clinical progression and the related biological biomarkers relevant to PCa progression in men on AS for PCa. Positive results from this study will be critical to inform development a phase III clinical trial and ultimately provide a strategy for secondary chemoprevention in men on AS, for whom, currently, there are no options for reducing risk of progression to PCa.

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