A Phase II Randomized Placebo Controlled Trial of Epigallocatechin-3-Gallate (EGCG) on Physical Frailty and Tumor Necrosis Factor-alpha and Associated Immune Markers in Older Cancer Survivors

University Of Rochester, Rochester NY

Investigators

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Abstract

Frailty is a significant problem for older (age 65+) survivors of cancer. Older survivors of cancer are at 46% greater risk of being physically frail compared to those without a history of cancer. No standard treatments for physical frailty in older survivors of cancer exist. Tumor necrosis factor-α (TNF-α) and related immune markers are associated with physical frailty in older survivors of cancer. Epigallocatechin-3-gallate (EGCG) is a potent anti-inflammatory nutraceutical that reduces TNF-α and related immune markers and risk of functional decline. EGCG is a promising intervention to reduce physical frailty in older survivors of cancer. This proposal builds upon my previous work demonstrating a relationship between cancer treatments, physical frailty, DNAmage, and TNF-α and related immune markers. My work also shows that an EGCG intervention (capsules with 800mg EGCG + 250mg Vitamin C) is safe and feasible in older survivors of cancer. This proposal presents a five-year complimentary research and career development plan. For this proposal I will conduct a Phase II, multicenter, 2-arm placebo controlled randomized clinical trial in 118 older survivors of cancer (aged 65+), who have completed cancer treatment (≤12 months) and are at least pre-frail (Fried Frailty Score ≥2) and randomized to the EGCG intervention or placebo for 12 weeks. The aims of the proposed study are: 1) To evaluate the preliminary efficacy of the EGCG intervention on physical frailty; 2) To evaluate the preliminary efficacy of the EGCG intervention on TNF-α and related immune markers; 3) To explore if baseline TNF-α and related immune markers and DNAmage are associated with baseline and post-intervention physical frailty; and 4) To explore the efficacy of the EGCG intervention on physical frailty and TNF-α and related immune markers across different population subgroups of older survivors of cancer. I will also complete the following new training goals: 1) To develop expertise to design, conduct, analyze and lead multicenter randomized clinical trials focused on nutraceuticals as interventions for frailty in older survivors of cancer; 2) To obtain training in epigenetics as a biomarker of frailty; 3) To gain expertise in strategies that improve the recruitment and retention of clinical trial participants, with the goal of enhancing representation to better reflect the general population. My mentorship committee includes national and international experts in nutraceutical and behavioral interventions, geriatric oncology, translational science, biostatistics, and recruitment and retention strategies. Under the guidance of Drs. Michelle Janelsins and Luke Peppone (primary mentors), Dr. Supriya Mohile (co-mentor), and Drs. Charles Kamen, Paula Vertino, Michael Sohn and Ms. Canin (advisors) I will obtain essential skills that I currently do not possess. The training and research plan will position me to achieve my long-term goal to become an independently R01-funded translational scientist in geriatric oncology who develops, and tests mechanistically driven, cancer control interventions.