Clinical trial NCT04553666
Conditions: Frailty Inflammation
Sponsor: University of Rochester
Start date: 2021-04-28; Completion date: 2023-08-31
Enrollment: 24 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the study is to examine the feasibility and safety of twelve weeks oral supplementation of Epigallocatechin-3-gallate (EGCG) in older survivors of cancer

Detailed description:

Arms: arm 1: Four 200mg EGCG pills and one 250mg Vitamin C pill taken one time each day arm 2: No study pills
Interventions: intervention 1: Epigallocatechin-3-Gallate (EGCG) plus Ascorbic Acid (Vitamin C)
Intervention descriptions: intervention 1: 800mg Epigallocatechin-3-Gallate (EGCG) plus 250mg Ascorbic Acid (Vitamin C) taken one time a day for twelve weeks

Protocol documents:
Prot_SAP_000.pdf: 
Protocol Date: January 20, 2023
1
UNIVERSITY OF ROCHESTER WILMOT CANCER INSTITUTE
Reducing Frailty for Older Cancer Survivors Using Supplements (ReFOCUS): A Phase 2 
Randomized Controlled Trial of Epigallocatechin-3-Gallate (EGCG) on Frailty and 
Inflammation in Older Survivors of Cancer
STUDY CHAIR:
Nikesha Gilmore, PhD
STUDY CO-INVESTIGATORS: 
Michelle Janelsins, PhD, MPH (Laboratory Chair)
Supriya Mohile, MD, MS
Luke J. Peppone, PhD, MPH
Erika Ramsdale, MD
Richard Dunne, MD (Medical Monitor)
Fergal Fleming, MBBCh
Charles Kamen, PhD
Beverly Canin (Patient Advocate)
BIOSTATISTICIAN: 
Eva Culakova, PhD, MS
STUDY PERSONNEL:
Adam Mitchell, BA
Lelaina DiLorenzo, BS


Protocol Date: January 20, 2023
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TABLE OF CONTENTS
STUDY SCHEMA ..........................................................................................................................4
1.0 STUDY OVERVIEW, PURPOSE, AND BACKGROUND ....................................................5
1.1 Purpose of the study...........................................................................................................................5
1.2 Background.........................................................................................................................................6
1.3 Preliminary data..................................................................................................................................9
1.4 Application of pilot data and background data to proposed study ..................................................11
1.5 Innovation and Clinical Importance:.................................................................................................12
2. HYPOTHESIS, STUDY DESIGN, AND AIMS ......................................................................13
2.1 Overall hypothesis ............................................................................................................................13
2.2 Study design......................................................................................................................................13
2.3 Specific aims .....................................................................................................................................13
2.4 Timeline ............................................................................................................................................14
3. CHARACTERISTICS OF THE RESEARCH POPULATION ................................................15
3.1 Subject characteristics and number of subjects ...............................................................................15
3.2 Gender, age, and racial/ethnic origin of subjects.............................................................................15
3.3 Inclusion and exclusion criteria.........................................................................................................16
3.4 Vulnerable subjects...........................................................................................................................16
4. SUBJECT IDENTIFICATION, RECRUITMENT, AND CONSENT.....................................17
4.1 Identification and Recruitment.........................................................................................................17
4.2 Screening ..........................................................................................................................................18
4.3 Consent process................................................................................................................................19
4.3.1 Written Consent: .......................................................................................................................19
4.3.2 e.Consent...................................................................................................................................19
4.4 Registration.......................................................................................................................................20
5. METHODS AND STUDY PROCEDURES .............................................................................21
5.1 Overview of study.............................................................................................................................21
5.2 Timing of assessments......................................................................................................................22
5.3 Data collection tables .......................................................................................................................23


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5.4 Screening assessment (T0)................................................................................................................24
5.5 Baseline assessment (T1)..................................................................................................................25
5.6 Randomization..................................................................................................................................33
5.7 Study Interventions (12 weeks’ duration).........................................................................................34
5.8 Study Drug ........................................................................................................................................34
5.9 Intervention contact and tracking ....................................................................................................34
5.10 Post-intervention assessment (T2) .................................................................................................35
5.11 Costs/Payments for participation ...................................................................................................36
5.12 Return of research results ..............................................................................................................36
6. SUBJECT WITHDRAWALS ...................................................................................................36
7. REPORTABLE EVENTS .........................................................................................................37
8. RISK/BENEFIT ASSESSMENT ..............................................................................................38
8.1 Risks to subjects................................................................................................................................38
8.2 Adequacy of protection against risk .................................................................................................39
8.3 Benefits.............................................................................................................................................41
8.4 Alternatives to participation.............................................................................................................41
9. CONFIDENTIALITY OF DATA AND DATA STORAGE....................................................41
9.1 Utilizing Research Electronic Data Capture (REDCap).......................................................................41
9.2 Data storage......................................................................................................................................42
9.3 Human blood samples ......................................................................................................................42
9.4 Assignment of study ID .....................................................................................................................42
10. RESEARCH INFORMATION IN MEDICAL RECORDS....................................................43
11. DATA ANALYSIS AND DATA MONITORING.................................................................44
11.1 Sample size determination .............................................................................................................44
11.2 Statistical analysis ...........................................................................................................................45
11.3 Data and Safety Monitoring Plan....................................................................................................45
12. REFERENCES ........................................................................................................................47


Protocol Date: January 20, 2023
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STUDY SCHEMA


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1.0 STUDY OVERVIEW, PURPOSE, AND BACKGROUND
1.1 Purpose of the study
Frailty, an aging-related clinical syndrome associated with low physiologic reserve, is a significant 
problem for older survivors of cancer.1,2 Frailty can be characterized by a combination of 
symptoms, such as low energy, weakness, slower walking speed, reduced participation in 
activities, and weight loss to calculate a score based on Fried’s frailty criteria. Our group has shown 
that older survivors of cancer (aged 65+) are at a 46% greater risk of being frail than those without 
cancer.3 For older adults with cancer receiving standard of care (surgery with or without 
chemotherapy), frailty predicts surgical complications, chemotherapy intolerance, and mortality.4-8 
Unfortunately, no effective treatments for frailty in older survivors of cancer exist. Recently, the 
National Cancer Institute (NCI) convened a panel of experts for a Think Tank on “Cancer-Related 
Accelerated Aging” and resolved that trials for frailty in older survivors of cancer are urgently 
needed.9  
Inflammation is a major contributor to frailty and a predictor of post-treatment frailty in patients 
with cancer.10-15  Due to the strong association between inflammation and frailty, interventions 
aimed at reducing inflammation may ultimately reduce frailty and improve post-treatment 
outcomes for older adults with cancer.  Dietary supplements such as epigallocatechin-3-gallate 
(EGCG) with known anti-inflammatory properties might serve as a practical approach to 
circumvent chemotherapy-induced frailty in older cancer survivors.16 
Frailty disproportionately affects African Americans/Blacks (AA/B) who also bear the highest 
cancer burden.17-20 AA/B have a four-fold increased odds of being frail compared to Whites and 
factors underlying this racial disparity in frailty are unknown.19 However, research shows that 
AA/B have elevated inflammatory markers which suggests that inflammation might contribute to 
the increased risk of frailty. Given the fact that older AA/B with cancer are underrepresented in 
clinical trials21 and are at the highest risk of frailty, it is imperative that trials are specifically 
designed to include this underrepresented group.
This is a two-arm phase 2, single site randomized controlled trial (RCT), oversampling for AA/B, 
to obtain preliminary data on the feasibility of a 12-week daily EGCG supplementation and on the 


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effects of this EGCG supplementation on frailty, inflammation, physical function, and quality of 
life in older survivors of cancer. Frailty will be assessed using the standardized Fried Frailty Score2 
(FFS) and the Deficit Accumulation Frailty Index (DAFI).22,23 In this study, 40 older adults (aged 
65+; ≥12 AA/B) who have completed curative intent treatment for stage I-III cancer within 10 
years who are pre-frail (have FFS ≥2) will be randomized to EGCG or usual care (UC) for 12 
weeks. We will acquire data via chart review, patient reports, clinical assessments, and blood 
draws. Our study aims are listed in section 2.3. We expect to complete data acquisition in 18 
months (≥4 patients per month, with around 8 (2 AA/B) meeting eligibility criteria per month). 
1.2 Background
Cancer, Aging, and Frailty. Older adults, aged 65+, account for more than 50% of new cancer 
cases and approximately 70% of mortalities due to cancer in the United States.24 As health care 
technology continues to advance, life expectancy will increase progressively, which in turn will 
result in a rapid increase in the number of older adults with cancer over the next two decades.25,26  
Additionally, as individuals age they accumulate a variety of aging related deficits (e.g. function, 
nutrition, cognition, and comorbidities) that can ultimately manifest as frailty.22 Frailty is 
characterized as an age-related syndrome that results in the decline of an individual’s physiologic 
reserves, leading to increased vulnerability to stressors. Frailty can be defined in two ways: 1) 
phenotypically using the standardized FFS: weakness, fatigue, low physical activity, slow walking 
speed, and unintentional weight loss;2 and 2) as an accumulation of aging related deficits 
determined by scores on the geriatric assessment that are used to create an index referred to as the 
Deficit Accumulation Frailty Index (DAFI).22 
In community dwelling older adults, frailty is associated with decreased quality of life, impairment 
in function and cognition, and risk of adverse outcomes such as disability and mortality.2,22,27,28 A 
diagnosis of cancer and its treatments are known stressors and contribute to the frailty phenotype. 
Thus frailty is prevalent in older adults with cancer, with > 50% of these patients classified as 
either pre-frail or frail.29 Frail older adults with cancer are more susceptible to over and under 
treatment, resulting in a variety of negative outcomes, including increased chemotherapy toxicity, 
decreased chemotherapy tolerance, and increased morbidity and mortality.3,30-33 
Frailty is a significant problem for older survivors of cancer.1,2 Treatment for stage I-III  cancer 
includes surgery with or without chemotherapy.8 Patients with cancer, especially older adults, 


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receiving treatment are at increased risk of frailty.29,Study1 Using a Medicare data-set, our group has 
shown that older survivors of cancer were at 46% increased risk of being frail compared to those 
without cancer.3 Furthermore, in older adults with cancer, frailty independently predicts surgical 
complications, chemotherapy intolerance, and mortality.4-7 There are limited interventions to 
improve outcomes for older survivors of cancer, thus trials for frailty in older cancer survivors 
were deemed as a NCI research priority.9
Inflammation and aging and frailty. Inflammation is the chief contributing factor to frailty.11,12,34 
Frail older adults have elevated TNF-α related immune responses demonstrated by increased levels 
of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), tumor necrosis factor receptor I and 
II (TNFRI/II), C-reactive protein (CRP), and interleukin-1β (IL-1β).12,13,35,36 These markers are 
also increased after surgery and chemotherapy37,38 and predict post-treatment frailty in patients 
with cancer.10,15 In my own research I have demonstrated that elevated levels of inflammatory 
cytokines and receptors in the TNF-α pathway (IL-6, TNFRI/II) pre-chemotherapy are similarly 
predictive of frailty after chemotherapy.10, Study3
The pleiotropic cytokine IL-6 is a soluble molecule involved in acute and adaptive immunity and 
functions to maintain homeostasis.39,40 Prior studies have shown that serum levels of IL-6 increase 
with age and that IL-6 may contribute to morbidity.13,34 In addition, IL-6 has been established as 
the main cytokine positively associated with Fried's phenotypic frailty.12,34 Lippitz et al. found that 
higher levels of serum IL-6 were highly correlated with mortality independent of cancer type and 
stage.41 IL-6 has also been found to increase after chemotherapy in patients with breast cancer.42 
TNF-α, another pleiotropic cytokine mainly produced by activated macrophages and monocytes, 
is a potent mediator of inflammation and is associated with frailty in older adults.35  TNF-α 
mediates its pro-inflammatory effects through the binding of its cognate receptors TNFRI and 
TNFRII. Soluble TNFRI and TNFRII (sTNFRI and sTNFRII), which are released via proteolytic 
cleavage of the membrane bound TNFRI and II, have been reported to be indicators of TNF-α 
production.43  It has been shown that frail individuals have elevated serum levels of sTNFRI and 
sTNFRII13, and this elevation is associated with chemotherapy treatments.44,45  
Other markers of inflammation have also been shown to be associated with frailty. The 
InCHIANTI study showed that high levels of IL-6, CRP, and interleukin receptor 1 (IL-1R) were 
associated with decreased physical performance, while IL-6 and CRP were associated with low 


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hand grip strength.46 The association of frailty with other markers of inflammation has also been 
described. In community dwelling older women, increased counts of circulating WBC, 
neutrophils, and monocytes were shown to be associated with frailty.47 In patients with cancer, 
increased WBC, neutrophils, and monocytes and decreased lymphocytes were associated with 
increased mortality.48,49 In patients with advanced colorectal cancer, elevated neutrophil to 
lymphocyte ratio (NLR) is predictive of poor prognosis.50 Additionally, in older patients with 
cancer, there is a positive association of NLR with frailty.51 Higher NLR was also shown to be 
negatively associated with instrumental activities of daily living (IADL) and increased time to 
complete the Timed-Up-and-Go (TUG) measure. 
Collectively, this interrelationship between inflammation, cancer, cancer treatments, and frailty 
supports the testing of anti-inflammatory agents as interventions for frailty in older survivors of 
cancer.
Epigallocatechin-3-gallate (EGCG) is a promising intervention for frailty. Numerous studies are 
evaluating non-steroidal anti-inflammatory drugs to treat cancer-related toxicities52,53 but its long-
term use is contraindicated in older adults.54 Thus, anti-inflammatory agents with low toxicity risk 
to treat frailty in older survivors of cancer are needed. EGCG is a tolerable anti-inflammatory 
dietary supplement and is associated with reduced functional decline in older adults.55 EGCG 
supplementation reduces TNF-α related immune responses, including levels of TNF-α, IL-6, and 
IL-1β.56-62 A completed Phase 2 trial using 800mg EGCG in patients with prior advanced colon 
adenoma or colon cancer, found that EGCG at this dose was safe, had low toxicity risk, and was 
well tolerated.63 The bioavailability of EGCG is both dose and pH dependent and pharmacokinetic 
studies showed that the daily supplementation of 800mg EGCG results in the highest serum 
concentration of EGCG64 and this is further enhanced by the simultaneous intake of 250mg 
ascorbic acid (vitamin C; VitC).65-67 In addition, intervention studies showed that 12-week oral 
supplementation of EGCG improved outcomes, such as weight loss in adults with obesity.68-71 
These data suggest that 800mg EGCG plus 250mg VitC taken for 12 weeks may be safe and 
efficacious in reducing inflammation and frailty in older survivors of cancer. Our proposed trial 
will be the first of its kind.
Addressing racial disparities in frailty in older adults with cancer is critical. Despite the fact that 
African Americans/Blacks (AA/B) bear the greatest burden of frailty and cancer,17-20 they are 


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underrepresented in oncology clinical trials21 and the causes of the racial disparity in frailty is 
unknown.19 Furthermore, AA/B account for 9% of the population of adults aged 65+ and this 
number is expected to increase to 13% by 2060.72 It has also been shown that AA/B have elevated 
inflammatory markers including CRP and IL-6 compared to Whites, which suggests that 
inflammation might play a role in the racial disparity of frailty.73 It is imperative that trials for 
older cancer survivors are designed to include AA/B, thus guide the development of health 
equitable interventions. 
Summary. Cancer treatment induced frailty is a significant burden to survivors of cancer. Safe and 
feasible interventions to reduce frailty in this population will be beneficial. Even though many 
trials have investigated the anti-tumor and cancer preventive properties of EGCG, none have 
investigated the role of this polyphenol in reducing frailty in older cancer survivors who have 
completed surgery with or without chemotherapy. This study serves as a feasibility trial of an 
EGCG intervention and to obtain preliminary data on the effect of EGCG on reducing 
inflammation and improving frailty, physical function, symptom burden, and quality of life and 
whether these effects differ by race. 
1.3 Preliminary data
Study 1: Chemotherapy worsens physical frailty of older patients with advanced cancer. In a 
subset analysis of 59 older patients (≥70 years) with advanced colon cancer about to start a new 
chemotherapy regimen from a multi-site study led by Dr. Mohile74, I showed that at baseline 76% 
of patients were physically frail using the Short Physical Performance Battery (SPPB75). Physical 
frailty increased with chemotherapy; SPPB score worsened in 37% of patients after 6 weeks and 
in 43% of patients after 3 months of treatment (Figure 1A). Physically frail compared to not frail 
patients at baseline had greater functional decline; more problems with activities of daily living 
after 6 weeks of treatment (mean SPPB change: 0.24 vs -0.77; p=0.04; Figure 1B) and more 
problems with instrumental activities of daily living after 3 months of treatment (mean SPPB 
change: 0.41 vs -0.70; p=0.04; Figure 1B). Physical frailty was also associated with mortality 
within 3 months of treatment (9% vs 0%).76


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Study 2: Cancer, surgery, and chemotherapy independently exacerbate frailty. Using data from 
a multi-site study led by Dr. Janelsins77, I found that patients (≥50 years) with breast cancer were 
more frail after surgery than those who had not yet started treatment (frailty score: 1.24 vs 1.01) 
using a modified Fried’s frailty score. I also published that patients (≥50 years) with breast cancer 
were more frail before chemotherapy than non-cancer controls (frailty score:1.17 vs 0.65; p<0.01; 
Figure 2A) and that the mean frailty score of patients with breast cancer increased from 1.17 to 
2.08 (p<0.01; Figure 2B) after chemotherapy.10 
A         Pre-Chemotherapy Time-point
B          Patients with Breast Cancer
Figure 2: Change in Frailty from the Pre-Chemotherapy to Post-Chemotherapy Time-point
Figure 1: Association of Physical Performance and Patient Reported Functional Decline


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Study 3: TNF-α related immune responses are associated with increased frailty after 
chemotherapy. Using the same data set from Study 2, I published that patients (≥50 years) with 
breast cancer with pre-chemotherapy TNF-α related immune responses above the median had 
worse frailty scores post-chemotherapy than those with levels below the median; IL-6 (2.31 vs. 
1.86; p=0.027), TNFRI (2.30 vs. 1.88; p=0.039), and TNFRII (2.30 vs. 1.88; p=0.039; Figure 3). 
No associations were found between TNF-α related immune responses and frailty in non-cancer 
controls. Pre-chemotherapy frailty was found to be a significant predictor of post-chemotherapy 
frailty.10
In addition, we examined the association of other markers of inflammation (lymphocytes, 
monocytes, neutrophils, total WBC, neutrophil to lymphocyte ratio (NLR), and lymphocyte to 
monocyte ratio (LMR)) with frailty in patients with breast cancer (mean age 53; range 22-81) 
between pre- and post-chemotherapy. We found that pre-chemotherapy WBC (β=0.04; p<0.01), 
neutrophils (β=0.04; p<0.01), and NLR (β=0.05; p<0.01) were associated with pre-chemotherapy 
frailty. From pre- to post-chemotherapy, greater increase in immune cells was associated with 
frailty (WBC: β=0.2; p<0.01, neutrophils: β=0.3; p<0.01, NLR: β=0.03; p<0.01) and greater 
changes in frailty (WBC: β=0.2; p<0.01, neutrophils: β=0.3; p<0.01, NLR: β=0.03; p<0.01). These 
associations remained significant after controlling for the receipt of growth factors with 
chemotherapy. 
1.4 Application of pilot data and background data to proposed study
Based on the literature and our preliminary data we propose the following model by which EGCG 
circumvents chemotherapy related inflammation, leading to a reduction in frailty and symptoms 
as well as an improvement in physical function and quality of life. The combined insult of cancer, 
A
B
C
Figure 3: Association of Pre-Chemotherapy Cytokines and Receptors and Post-Chemotherapy Frailty


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surgery, and adjuvant chemotherapy results in a heightened inflammatory state characterized by 
elevated pro-inflammatory molecules, increased circulating immune cells, and disruption in the 
homeostasis of the ratios of immune cells. Prolonged exposure to this inflammatory state may 
cause insults to a variety of organ systems that ultimately manifest as frailty. This frail state can 
then lead to increased symptoms, decreased quality of life, and decreased physical performance. 
Theoretical Framework: EGCG is a promising intervention for frailty but has not been 
systematically studied. We will determine the safety, feasibility, and efficacy for EGCG on 
reducing frailty and TNF-α related immune responses in older cancer survivors and explore 
whether there are any differences by race and treatment type in the efficacy of this intervention. 
We will also explore the effect of EGCG on physical performance, symptoms, and quality of life.  
We hypothesize that EGCG is safe and will improve frailty in older cancer survivors by reducing 
TNF-α related immune responses (as measured by serum levels of TNF-α, TNFRI, TNFRII, IL-6, 
IL-1β, and CRP) and circulating immune cells (as measured by lymphocytes, monocytes, 
neutrophils, total WBC, NLR, LMR) (Figure 4). 
1.5 Innovation and Clinical Importance: 
Our research proposal is innovative because: 1) This study will be the first to examine EGCG as 
an intervention for frailty resulting from TNF-α related immune responses in older cancer 
survivors; 2) This study includes both older adults and AA/B; two populations that are typically 
marginalized in oncology trials. Preliminary data from this study will be leveraged to support a 
future NCI K01 (career development) application to conduct a Phase 2, 2-arm randomized 
placebo-controlled trial in older cancer survivors with a focus on AA/B.
Figure 4: Theoretical Model


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2. HYPOTHESIS, STUDY DESIGN, AND AIMS
2.1 Overall hypothesis
We hypothesize that EGCG supplementation will reduce markers of inflammation and frailty, is 
safe and feasible, and will improve physical function, patient reported symptoms, and quality of 
life in older patients with cancer post-surgery with or without chemotherapy.
2.2 Study design
We propose a two arm single-site phase 2 randomized clinical trial (RCT) in older adult (aged 
65+) cancer survivors to test a 12-week intervention of EGCG supplementation compared to usual 
care on frailty, inflammation, symptom burden, and quality of life. A phase 2 RCT design was 
chosen to help determine the effect size of the intervention, as EGCG interventions have not 
previously been tested in this population of older adults. Assessments will occur at baseline (≤10 
years after the completion of curative intent cancer treatment and post-intervention (12 – 13 weeks 
after baseline).
Forty patients with cancer over the age of 65 who have completed curative intent cancer treatment 
for stage I-III cancer will be randomly assigned to: Arm 1: 800mg EGCG + 250 mg VitC 12 weeks 
or Arm 2: Usual care
Our intervention involves oral supplementation of EGCG taken orally at home. Using screening, 
baseline, and post-intervention measures, we will assess frailty, inflammation, symptom burden, 
physical function, and quality of life and how these change over the intervention period. We also 
propose to bank blood samples for future proteomic and epigenetic studies. 
2.3 Study Outcomes
Aim 1: To determine the feasibility and safety of conducting a two arm RCT as measured by 
recruitment rate, adherence to study procedures and EGCG intervention, and adverse events.
Aim 2: To obtain preliminary data on the effects of EGCG vs UC on frailty measured by FFS 
(weight loss, weakness measured by hand-grip dynamometry, slowness measured by 4 meter walk 
test, physical activity measured by the GODIN Leisure-Time Physical Activity, and exhaustion 


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measured by the symptom inventory) and the Deficit Accumulation Frailty Index (DAFI) based 
on the geriatric assessment.
Aim 3: To obtain preliminary data on the effects of EGCG vs UC on TNF-α related immune 
responses (measured by serum levels of TNF-α, TNFR I, TNFRII, IL-6, IL-1β, and CRP) and 
circulating immune cells as measured by lymphocytes, monocytes, neutrophils, total WBC, NLR, 
LMR in older survivors of CC.
Exploratory Aims: 
1) To explore if there are racial (AA/B vs White) or treatment differences in the effects of EGCG 
on frailty and TNF-α related immune responses.
2) To obtain preliminary data on the effects of a 12 week oral EGCG supplementation compared 
to usual care on patient reported outcomes (symptom burden as measured by the MD Anderson 
Symptom Inventory (MDASI) and quality of life as measured by the Functional Assessment of 
Cancer Therapy – Colon Cancer (FACT-C) or FACT-General) and physical function (measured 
by Timed up and Go (TUG), Short Physical Performance Battery (SPPB), and Yale Physical 
Activity Survey). 
3) To explore transcriptomic and epigenetic differences (using isolated PBMCs) between older 
pre-frail and frail cancer survivors. 
4) To perform qualitative analysis in order to gain insights into the frailty experience of older 
cancer survivors. (post-adjuvant treatment).
2.4 Timeline
We expect to complete data acquisition in 18 months (≥4 patients per month, with around 8 (2 
AA/B) meeting eligibility criteria per month). We anticipate spending about 1.5 years analyzing 
data, using the data in support of external grants, and disseminating scientific findings.


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3. CHARACTERISTICS OF THE RESEARCH POPULATION
Total Planned Enrollment: 40 
TARGETED/PLANNED ENROLLMENT: Number of Subjects
Sex/Gender
Ethnic Category
Females
Males
Total
 Hispanic or Latino
1
1
2
 Not Hispanic or Latino
19
19
38
 Ethnic Category: Total of All Subjects
20
20
40
Racial Categories
 
 American Indian/Alaska Native
0
0
0
 Asian
1
1
2
 Native Hawaiian or Other Pacific Islander 
0
0
0
 African American or Black (AA/B)
6
6
12
 White
13
13
26
 Racial Categories: Total of All Subjects 
20
20
40
3.1 Subject characteristics and number of subjects
We will recruit 40 older patients (≥65 years) within 10 years of completing curative intent for stage 
I – III cancer. 
3.2 Gender, age, and racial/ethnic origin of subjects
As shown in the table above, we will attempt to over recruit African American/Black subjects 
because they are underrepresented in clinical trials and have increased risk of frailty.
Children, as defined by the National Institutes of Health Grants Policy Statement, will not be 
included because of our eligibility criteria.


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3.3 Inclusion and exclusion criteria
Inclusion Criteria: Study subjects must:
1. Be age 65 or over.
2. Be diagnosed with stage I-III Cancer 
3. Have completed curative intent treatment ≤10 years prior to screening 

Patients on endocrine therapies are allowed to enroll
4. Have a Fried’s Frailty Score (FFS) of ≥ 2 
5. Able to provide informed consent, or have consent given by patient-designated health care 
proxy per institutional policies and University of Rochester Cancer Control URCC 
guidelines. 
Exclusion Criteria: Study subjects must not:
1. Have chemotherapy planned for the duration of the study.
2. Have abnormal liver function tests (ALT, AST, and bilirubin ≥ 3 times institutional upper 
limit of normal) per most recent available lab test (within 3 months of screening). 
3. Have uncontrolled or unmanaged liver disease.
4. Consume more than 6 cups of green tea per day.
5. Have known allergies to caffeine.
6. Be diagnosed with a major psychiatric illness requiring hospitalization within the last year. 
7. Be diagnosed with dementia.
8. Cannot provide informed consent due to lack of decision making capacity (as determined 
by the patient’s oncologist) and has no patient-designated health care proxy per 
institutional policies and University of Rochester Cancer Control URCC guidelines. 
3.4 Vulnerable subjects
This study will only recruit subjects >65 years. Subjects with lack of decision making capacity (as 
determined by the patient’s oncologist) may be enrolled provided that they have a healthcare proxy 
who co-signs consent, attends study visits, and is available for follow-up phone calls.


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4. SUBJECT IDENTIFICATION, RECRUITMENT, AND CONSENT
4.1 Identification and Recruitment
We will recruit subjects using our group’s established procedures. Before recruitment we will 
obtain approval by the Institutional Review Board (IRB). We will identify and recruit patients 
using medical records, advertisements in cancer clinics, and direct referral from nurses and 
physicians. 
Identification and recruitment via eRecord medical records and MyChart. We will identify 
potential patients who have completed cancer treatment for cancer ≤10 years prior to screening 
(i.e. ≤10 years of completing curative intent treatment). 
Study personnel will screen medical records of potentially eligible subjects and confirm 
with/obtain physician permission to approach the patients. Alternatively, we will let potentially 
eligible subjects know about the study using MyChart for recruitment at the University of 
Rochester Medical Center. 
Using the study inclusion/exclusion criteria, potential subjects will be identified using information 
available in eRecord. The study team will review eRecord data on these subjects in order to 
determine eligibility for this study. Data elements that will be reviewed include: patient’s age, 
cancer diagnosis, last date of cancer treatment, and patient’s race. 
Potentially eligible subjects will receive an email or text notifying them that they have a new 
research opportunity available in MyChart. It can only be viewed after they log in to MyChart and 
visit the Research Studies page. Subjects will see a description of the study, which is included on 
the attached MyChart for Recruitment Request form (uploaded as part of recruitment materials). 
Underneath the study description on the Research Studies page, subjects will indicate whether or 
not they are interested in participating by clicking on the corresponding button. This will trigger a 
notification that is sent to the study coordinator’s InBasket in eRecord.
Interested subjects will then be contacted for screening as described in this protocol. Subjects who 
are not interested will not be contacted and will be removed from the pool of eligible subjects. If 
subjects do not indicate whether or not they are interested in participating, they may be re-sent the 
email notification one additional time, no sooner than one week after the first email was sent. 


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When study accrual has been completed, outstanding research opportunities in MyChart will be 
rescinded.
Identification and recruitment via advertisements in cancer clinics and related sites. Our RSRB-
approved advertisements will be displayed in cancer clinics, local sites of interest, and social media 
(e.g., Clinical Translational Science Institute, University of Rochester) and distributed by 
clinicians and clinical staff. The advertisements contain information about the study duration, 
assessments, and eligibility criteria. If the patient is interested, they can contact the study team 
(e.g., the study coordinator or principal investigator (PI) via phone or email) to discuss the study, 
determine likelihood of eligibility, ask for permission to contact the patient’s physician for their 
approval, and set up a time to conduct the informed consent discussion in a private location.
Identification and recruitment via direct referral from nurses and physicians. We are working 
with several oncologists (including, but not limited to our co-investigators Drs. Dune, Ramsdale, 
and Fleming) and their medical team (e.g., nurses, nurse practitioners) to identify potential patients 
at the University of Rochester and affiliated Wilmot Cancer Institute locations (e.g., Interlakes 
Oncology and Hematology) who are likely eligible for our study. If the patient is eligible based on 
information in the medical records and from the physician and medical team, we will request that 
the physician refer the patient to us or obtain the physician’s permission to contact the patient to 
discuss our study and to conduct the informed consent discussion if the patient is interested in the 
study. 
For the convenience of the patient, we will make every effort to meet the patient at their clinic 
appointment for these discussions. To protect the privacy of potential subjects, we will conduct 
recruitment discussions in a private location. In the event that we are not able to complete in person 
visits, study information (as appropriate) will be collected by phone or Zoom and questionnaires 
will be completed by either by mail, electronically, or via Zoom or phone as per patient preference. 
To aid in recruitment, we may mail a letter and brochure to the patient describing our study. 
4.2 Screening 
A study staff member will meet the patient in person or via phone to explain the project, recruit, 
and screen per inclusion and exclusion criteria in section 3.3. We will obtain as much information 
ahead of time as possible from medical records. If we are meeting with the patient via phone, we 


Protocol Date: January 20, 2023
19
will familiarize the patient with our study and obtain basic eligibility information that was not 
obtained via medical records. 
To ensure we do not approach the same subject twice, we will keep a screening log containing the 
following information:

Screening ID (S1, S2, S3, …)

Subject name

Date of contact

Medical record number

Gender

Race/ethnicity

Where/how we talked to the patient (e.g., phone)

Whether the patient was eligible or not

If ineligible, the reason they are ineligible

Whether the patient consented or declined

If declined consent, the reason for declining consent

If consented, the subject ID in the study (C1, C2, C3, …)
All subjects will need medical clearance from their oncologist (or designee) to participate in the 
intervention. To familiarize the clinical team with our study procedures we will provide a summary 
of the study protocol. 
4.3 Consent process
Current state, federal, and institutional regulations concerning informed consent will be followed. 
Three scenarios for consenting will be used.
4.3.1 Written Consent: 
For eligible patients who are interested in participating, a study member (coordinator, chair, co-
investigator, etc.) will give the patient a copy of the IRB approved consent form. The consent form 
will be carefully reviewed including the duration of the study with the patient and health care proxy 
(if applicable) to ensure comprehension.  If a patient lacks capacity, a health care proxy will be 
required to sign consent per institutional or local policies on consent for incapacitated/decisionally 
impaired subjects. If the patient does not have an appointed health care proxy on or before the 


Protocol Date: January 20, 2023
20
baseline visit, he/she will not be enrolled onto the study. All consent documents will be signed by 
the patient and/or designated health care proxy and maintained in the patient record with copies 
provided to the patient and/or designated health care proxy.  The study member will be available 
to answer any questions the patient may have about any aspect of the study prior to consenting and 
throughout the entire study period. To reduce behavioral artifacts, we will blind subjects to our 
study’s hypotheses using neutral language regarding the efficacy of the study drug on frailty and 
other outcomes. Patients may choose to sign the informed consent immediately on the day the 
study information is presented to them or they may choose to take the consent form home and 
discuss it with others. If a patient agrees to participate, a study team member or investigator and 
the subject will also sign the consent form.  If the patient decides to take the consent form home 
they will receive a follow-up call from study personnel. If patient agrees to participate in the study, 
they may sign the consent from at the next meeting with the study team member or investigator. 
A copy of the signed consent form will be given to the subject. All consent documents will be 
maintained in the patient record. 
4.3.2 Verbal Consent
If the patient is not able to be approached at one of their survivorship oncology appointments, 
study personnel will call the patient using the IRB-approved telephone script for consent. The 
conversation and a copy of telephone script will be part of the subject’s record. The patient will be 
given and asked to sign the full consent form at their next visit. This mechanism will minimize 
patient burden as they will not need to travel for an extra appointment to sign consent. It will also 
help to schedule study procedures in a timely way. The patient will also be given the option to 
complete the consent form by mail. See section 4.3.3
4.3.3 Mail Consent
After completing the verbal consent, if the patient prefers to complete the consent form by mail 
then two consent forms will be mailed to the patient. The patient will also be sent a form with 
detailed instructions on completing the consent form and mailing back completed documents.  
Subjects are to sign both copies, and send both back with the provided mailing materials. Thus, 
the packet sent to the subject will contain:

Two content forms

An informational letter with detailed instructions to correctly complete the consent form


Protocol Date: January 20, 2023
21

A self-addressed stamped envelope for the subject to include both signed copies of the 
consent forms
The consenting person will then sign both copies and either:

Send one completed document (with both signatures) back to the subject by mail OR 

Give the subject at their next study visit
The second completed consent form will be added to subject’s research folder. If after the verbal 
consent, the patient completes the written consent by mail it should be noted that there will be a 
difference in the dates of the signature for the patient and the coordinator.  
After consent, additional study forms will be used to fully assess eligibility (e.g. forms associated 
with FFS).
4.4 Registration
For subjects who are eligible and who provide written informed consent or verbal consent, the 
following information will be entered into a master list using either Research Electronic Data 
Capture (REDCap) or another secure electronic database (e.g., password-protected Excel database 
on a password-protected networked drive). This information is needed to contact subjects during 
the study to troubleshoot any issues, remind them of study appointments, etc.:

Subject ID number (used to identify the subject on all study forms and lab specimens)

Subject name

Subject phone number

Subject email address

Subject address of residence including nine-digit zip code

Birth date (MM/DD/YYYY)

Gender

Race

Cancer primary site

Documentation of cancer stage, surgery, and completed cancer treatment regimen

Most recent IRB approval date

Name of person registering study subject

Eligibility verification (FFS)


Protocol Date: January 20, 2023
22

Treatment facility

All the information listed above in the Screening Log (Section 4.2)
5. METHODS AND STUDY PROCEDURES
5.1 Overview of study
This is a two arm RCT evaluating a 12-week nutritional supplement (EGCG) compared to usual 
care on inflammation, frailty, symptom burden, physical performance, and quality of life in 40 
older patients who have completed curative intent cancer treatment. Subjects will complete 
questionnaires, clinical assessments, and a blood draw at two time points: baseline (week 0, T1) 
and post-intervention (approximately week 13, T2). After the subject is consented, they would 
complete the screening, where the subject will complete Fried’s frailty measures to determine FFS 
and confirm eligibility. Subjects eligibility by the FFS must be confirmed before randomization, 
which will occur at the screening/baseline assessment. At the post-intervention assessment, 
subjects will be interviewed (with an optional audio recording) and will also complete a study 
feedback form.                                                                                                                                                            
To ensure appropriate safety precautions when conducting in-person study procedures, the process 
for conducting in-person visits outlined in the Guidance for Human Subject Research will be 
followed.
Some assessments will be conducted in the laboratory due to requirements of the facilities and 
equipment; some assessments will be conducted in Wilmot Cancer Institute clinics.  Blood will be 
drawn by trained phlebotomists at UR-affiliated blood labs. The processing of blood samples will 
occur in the Cancer Control and Psychoneuroimmunology Lab (director: Dr. Janelsins), the 
Wilmot Cancer Center, or a UR-affiliated blood lab. Paper versions of the questionnaires can also 
be mailed to the patient’s home prior to the baseline (week 0, T1) and/or post-intervention 
assessment (approximately week 13, T2) or completed in the Wilmot Cancer Institute clinics.
Due to safety precautions needed as a result of COVID-19, in lieu of some in person assessment, 
the virtual format of some assessments (such as SPPB and MoCA) will be conducted.  


Protocol Date: January 20, 2023
23
5.2 Timing of assessments
Screening assessment T0 must be completed no more than 10 years after the completion of 
subject’s curative intent cancer treatment. This timing is to ensure that lasting effects of curative 
intent cancer treatment immune system are minimized and that frailty is still likely to be present. 
This time frame is also consistent with other survivorship clinical trials.
Assessments T0 and T1 can be completed on the same day. In the event that assessment T0 and 
T1 are completed on different days, assessment T1 should not occur more than 4 weeks after T0. 
If for some reason T1 occurs more than 4 weeks after T0, Fried’s frailty measures must be repeated 
to ensure that subjects still meet eligibility criteria. Optimally, assessments T0 and T1 will occur 
on the same day or within 1 week.
Optimally, assessment T2 will occur during week 13 (within the first week after the completion of 
study drug), but this may be adjusted (for to no more than 3 weeks after the completion of the 
study drug) to accommodate factors such as the clinical, subject, and researcher’s schedule.
The following table details the approximate study timeline.
Table 1: Approximate study timeline
Study week
0
1
2
3
4
5
6
7
8
9
10
11
12
13
Study 
activities
Consent 
T0
T1*
T2
*Optimally T1 occurs within 1 week after T0 or on the same day.
5.3 Data collection tables
The following table summarizes study activities based on the 12-week intervention that all subjects 
will complete regardless of randomization assignment (EGCG or usual care).
Table 2: Schedule of Activities 
Screening 
Baseline
Post-
Intervention
(week 0)
(week 13) 
Assessment
Study Goal
Completed 
by
T0
T1
T2
Written Informed 
Consent
N/A
Subject
●
 
 
Demographics
Eligibility
Subject
●
 
Eligibility 
Checklist
Eligibility
Research 
Assistant
●
Clinical Record 
Form
Eligibility A2/EA1
Research 
Assistant
●
 


Protocol Date: January 20, 2023
24
Fried's Frailty 
Score (FFS)
Eligibility/ A2/EA1
Research 
Assistant
●
 
●
GODIN Leisure-
Time Exercise 
Questionnaire
Eligibility
Research 
Assistant
●
●
Instrumental 
Activities of Daily 
Living
GA/A2/EA1
Subject
 
●
●
Activities of Daily 
Living
GA/A2/EA1
Subject
 
●
●
Patient Rated 
Karnofsky 
Performance Status 
(Patient KPS)
GA/A2/EA1
Subject
 
●
●
Fall History
GA/A2/EA1
Subject
 
●
●
OARS 
Comorbidity
GA/A2/EA1
Subject
 
●
●
Social Activities
GA/A2/EA1
Subject
 
●
●
OARS Medical 
Social Support
GA/A2/EA1
Subject
 
●
●
Geriatric 
Depression Scale 
(GDS)
GA/A2/EA1
Subject
 
●
●
Generalized 
Anxiety Disorder-7 
(GAD7)
GA/A2/EA1
Subject
 
●
●
Functional 
Assessment of 
Cancer Therapy: 
General (FACF-G)
EA2
Subject 
(diagnosed 
with any 
cancer 
except 
colorectal)
●
●
Functional 
Assessment of 
Cancer Therapy: 
Colorectal Cancer 
(FACT-C)
EA2
Subject 
(diagnosed 
with 
colorectal 
cancer)
 
●
●
MD Anderson 
Symptom 
Inventory 
(MDASI)
EA2
Subject
 
●
●
Mini Nutritional 
Assessment (MNA)
GA/A2/EA1
Research 
Assistant
 
●
●
Physician Rated 
Karnofsky 
Performance Status 
(KPS)
GA/A2/EA1
Research 
Assistant
 
●
●
Labs
GA/A2/A3/EA1/EA3
Chart 
Review
 
●
●
Blood Requisition 
Form
A3 & EA3
Phlebotomist
 
●
●
Montreal Cognitive 
Assessment 
(MoCA)
GA/A2/EA1
Research 
Assistant
 
●
●


Protocol Date: January 20, 2023
25
Short Physical 
Performance 
Battery (SPPB)
EA2
Research 
Assistant
 
●
●
Timed up and Go
EA2
Research 
Assistant
 
●
●
Yale Physical 
Activity Survey for 
Older Adults
EA2
Research 
Assistant
 
●
●
Qualitative 
Interview (Audio 
Recorded)
EA4
Research 
Assistant
 
 
●
Pill Count Form 
(Excel)
A1
Research 
Assistant
 
 
●
Weekly Phone Call 
Log (Excel)
A1
Research 
Assistant
 
●
●
Study Feedback 
Form
A1
Subject
 
 
●
Not Applicable (N/A); Geriatric Assessment (GA); Aim 1 (A1); Aim 2 (A2); Aim 3 (A3); Exploratory 
Aim 1 (EA1); Exploratory Aim 2 (EA2); Exploratory Aim 3 (EA3); Exploratory Aim 1 (EA4)
5.4 Screening assessment (T0)
Fried’s frailty measure will be completed after consent is obtained from the subject in order to 
confirm eligibility. Fried will be characterized as a combination of symptoms (such as low energy, 
weakness, slower walking speed, reduced participation in activities, and weight loss). This 
measure should take 5-10 minutes to complete. The following will be used to determine the 
subjects Fried’s Frailty Score (FFS) and will be reassessed during the post-intervention (T2) 
assessment. 78
 
FFS will be assessed using the 5 characteristics listed in Table 3. For each characteristic, subjects 
will receive a score of one if they met the cut-off for that characteristic. The scores will be summed. 
Total scores can range from zero to five to represent FFS, with zero indicating that they did not 
Table 3: Fried Frailty Score (FFS)
Slowness
time to walk 4 meters based on height: ≤0.65m/s for height ≤1.59m; ≤0.76 m/s for height 
>1.59m 
Weakness
grip strength/body mass index (BMI): ≤17 for BMI 23-26; ≤18kg for BMI 26-29; ≤21kg for 
BMI >29
Weight loss 
>10lb lost unintentionally in the last year/last visit or BMI<18.5
Physical 
Activity
GODIN Leisure Score Index- Activity/week: Score ≤23 equivalent to <14 Kcal/kg/week
Fatigue
answer yes to any of the following (low usual energy level; unusually weak or tired in the 
last month)


Protocol Date: January 20, 2023
26
meet any cut offs, and five meaning that they met all five cut offs. FFS was chosen because it can 
quickly assess frailty in outpatient settings, has good construct, convergent, concurrent, and 
predictive validity, and is sensitive to change following an intervention.2,61-64 Subjects can be 
classified into three frailty groups based on the FFS: FFS= 0 is classified as robust/not frail, FFS= 
1 or 2 classified as pre-frail, and FFS= 3-5 classified as frail.
5.5 Baseline assessment (T1)
The following assessments will be completed prior to randomization, preferably within one week 
of screening assessment (T0). Subjects have the option of completing the screening and baseline 
assessments on the same day. Due to the ongoing COVID-19 pandemic, some of the baseline 
measures may be completed either in person, via phone or Zoom. 
Demographics, clinical and treatment/cancer characteristics will be collected. 
Socio-Demographics and Clinical Characteristics
Patient’s age, race, ethnicity, gender, highest level of education achieved, employment 
status, and marital status, will be captured from the subjects. The socio-demographics and 
clinical characteristics will be collected at baseline.
Clinical Record Form
Type of colorectal neoplasm, prior malignancy, and treatment regimen will be abstracted 
from the medical records. This information will be collected at baseline only.
Outcomes of Interest (baseline and post-intervention unless otherwise specified)
Geriatric Assessment Measures for DAFI calculation 
Items from the Geriatric Assessment will be used to calculate the deficit accumulation 
frailty index (DAFI) to assess subjects’ frailty status at the baseline assessment (T1) and at 
the post-intervention assessment (T2).
Activities of daily living (ADL): ADLs are measures of self-care. ADL 
independence will be assessed using the Katz Index of Independence in Activities 
of Daily Living, commonly referred to as the Katz ADL. The Katz ADL is the most 
appropriate instrument to assess functional status as a measurement of the client’s 


Protocol Date: January 20, 2023
27
ability to perform activities of daily living independently. Clinicians typically use 
the tool to detect problems in performing activities of daily living and to plan care 
accordingly. The index ranks adequacy of performance in the six functions of 
bathing, dressing, toileting, transferring, continence, and feeding. Clients are scored 
yes/no for independence in each of the six functions. A score of 6 indicates full 
function, 4 indicates moderate impairment, and 2 or less indicates severe functional 
impairment.
Instrumental Activities of Daily Living (IADL): Self-reported functional status will 
be assessed using the IADL subscale of the Multidimensional Functional 
Assessment Questionnaire: Older American Resources and Services (OARS). The 
IADL subscale consists of seven questions rated on a three-point Likert scale. It 
measures the degree to which an activity can be performed independently.
Fall History: A self-reported history of falls in the past three months will be 
recorded. A history of a recent fall has been demonstrated to be independently 
predictive of increased risk for chemotherapy toxicity in older patients with 
cancer.79 
Timed Up and Go:  The Timed Up & Go is a performance based test of functional 
status, measuring how many seconds it takes to stand up from a standard arm-chair, 
walk 3 meters (10 feet), turn, walk back to the chair, and sit down again. 
Nutritional Status and Mini Nutrition Assessment (MNA):  Screening for nutritional 
deficit will be performed with body mass index (BMI) evaluation and self-reported 
weight loss.  Further nutritional evaluation will be performed with the Mini-
Nutritional Assessment (MNA), a well validated screening measure for nutritional 
deficiency which has shown to be prognostic of survival in older patients with 
cancer. Weight will be assessed at the screening assessment (T0) and at the post-
intervention assessment (T2).  Height will be assessed at baseline. 
Cognition: Montreal Cognitive Assessment (MoCA): A 30-point cognitive screen 
test with excellent sensitivity for individuals with mild dementia and mild cognitive 
impairment. It can also be used to trend changes in cognitive status over time.   


Protocol Date: January 20, 2023
28
Comorbidity: OARS Physical Health Section: Patients self-report their coexisting 
medical conditions and also rate the degree to which their illness causes impairment 
in daily activities. The OARS Physical Health Section has been shown to correlate 
significantly with health professional ratings of comorbidity as well.
OARS Medical Social Support and Social Activities:  A 13-question survey asking 
patients to identify the number of support persons involved in their medical care as 
well as the degree to which they felt supported in a variety of situations. A follow-
up question will be used to assess how much a patient’s physical or emotional 
health interfered with social activities. 
Medications (baseline only): We will record all prescription and non-prescription 
medications, dosage and frequencies from the medical records. We will also do 
medication reconciliation with the oncology team to determine the accuracy of all 
possible medications that the subject is taking. Polypharmacy is defined as the use 
of 5 or more medications.
Generalized Anxiety Disorder 7 (GAD-7):  The GAD-7 is a self-administered 
patient questionnaire used as a screening tool and severity measure for generalized 
anxiety disorder. The GAD7 score is calculated by assigning scores of 0, 1, 2, and 
3, to the response categories of “hardly ever,” “several days,” “more than half the 
days,” and “nearly every day,” respectively, and adding together the scores for the 
seven questions.  Scores of 5, 10, and 15 are taken as the cut off points for mild, 
moderate, and severe anxiety, respectively. When used as a screening tool, further 
evaluation is recommended when the score is 10 or greater.  Using the threshold 
score of 10, the 
GAD-7 has a sensitivity of 89% and a specificity of 82% for generalized anxiety 
disorder.  It is moderately good at screening three other common anxiety disorders 
– panic disorder (sensitivity 74%, specificity 81%), social anxiety disorder 
(sensitivity 72%, specificity 80%), and post-traumatic stress disorder (sensitivity 
66%, specificity 81%).80 


Protocol Date: January 20, 2023
29
Geriatric Depression Scale (GDS): Patients will be screened with the Geriatric 
Depression Scale (GDS). The GDS contains questions that are intended to screen 
elderly patients for depression, while parsing out complaints related to advanced 
age. 
Other Measures for DAFI calculation
Physician rated Karnofsky Performance Status (KPS): The KPS is an index that 
allows patients with cancer to be classified according to the presence of any 
functional impairments (e.g. inability to work and care for personal needs). KPS 
score ranges from 0-100. Low KPS scores are associated with decreased survival 
in patients with cancer.
Patient rated KPS: The patient rated KPS is a patient reported outcome of the 
presence of any functional impairments.
Complete Metabolic Panel (CMP): Study personnel will obtain lab results from the 
CMP from electronic medical records with dates that are closest to assessment date 
for baseline assessment (T1) and post-intervention assessment (T2).
Table 4: Measures Needed to Calculate the Deficit Accumulation Frailty Index (DAFI)
Measure 
Item
Demographics
Marital Status
Telephone
Travel
Shopping
Prepare Meals
Housework
Take Medicines
IADL Instrumental Activities of Daily Living 
(IADL)
Handle Money
Bathing/showering
Dressing
Eating
Getting out of bed or chairs
walking 
Activities of Daily Living (ADL)
Using the toilet
Patient rated Karnofsky Performance Status
Patient Rated KPS
Fall History
Number of Falls
Polypharmacy
Number of regular medications taken daily
Other cancer or leukemia
Arthritis
Glaucoma
Emphysema
OARS Comorbidity
High blood pressure


Protocol Date: January 20, 2023
30
Heart disease
Circulation trouble
Diabetes
Stomach/Gastrointestinal 
Osteoporosis 
Liver/kidney
Stroke
Depression
Eyesight
Hearing 
Mini Nutritional Assessment (MNA)
Weight loss
Geriatric Depression Scale (GDS)
Depression
Generalized Anxiety Disorder -7 (GAD7)
Anxiety
Social activity
Change of social activity in the last 6 months
Social activities
Comparison of social activity to others their age
Confined to bed
Take to MD
Prepare Meals
OARS Medical Social Support
Daily chores
Physician Rated Karnofsky Performance 
Status
KPS
Timed-up-and-go (TUG) 
Time to complete measure
Montreal Cognitive Assessment (MoCA)  
Cognition 
Mini Nutritional Assessment (MNA)
Body Mass Index
Creatinine clearance
Hemoglobin
Albumin
Complete Metabolic Panel
Liver Function test
Assessment of inflammatory markers 
We will assess the blood concentrations of several immunological proteins 
(primary aim) and EGCG (only at the post-intervention time-point (T2)). All blood 
draws will occur in the Wilmot Cancer Center, UR-affiliated lab, or medical office 
if needed (in the latter case, we will use a trained study staff member to transport 
the samples to our storage facility). The location will be selected to minimize 
subject burden and if possible we will perform blood draws at the same time as 
regularly scheduled medical blood draw. Patients will report for the blood draw 
fasted for a minimum of 8 hours on the days of the scheduled blood draws. The 
blood will be drawn by trained staff and subjects will be informed to bring a 
breakfast/a snack to eat after the blood draw. The time of day will be noted, with 
future assessments at approximately the same time of day during post-testing.


Protocol Date: January 20, 2023
31
A total of approximately 65-70 mL of blood (around 5 tablespoons) will be drawn 
at each time point (T1 and T2). All tubes will be collected by a study team member, 
processed, and then transferred to a secured -80°C freezer in lab space maintained 
by Dr. Janelsins in the Department of Surgery. We will collect the following:
1. Two red-top tubes for serum (10 mL each, 20 mL total). These tubes will be 
inverted 10 times, allowed to clot for 30 minutes at room temperature, 
centrifuged for 15 min at 1600 g and then frozen at -20°C or -80°C. These will 
be used to assess inflammation (cytokines, etc.) and EGCG concentration (only 
at the post-intervention time-point (T2)).
2. Two purple-top EDTA tubes for biological plasma levels (10 mL each, 20 mL 
total). One EDTA tube will be rocked 10 times, stored upright for a minimum 
of 30 min at room temperature and then spun. The other EDTA tube will be 
rocked 10 times and frozen at -20°C for 2-24 hours and then frozen at -80°C. 
These will be used to assess genetic biomarkers.
3. Two green-top tubes for peripheral blood mononuclear cells (10 mL each, 20 
mL total). These will be pre-cooled and processed per SOP. This tube will be 
inverted 10 times and allowed to sit at room temp for 30 minutes, centrifuged 
for 15 min, and then frozen at -20°C or -80°C. These samples will be used to 
explore transcriptomic and epigenetic differences (using isolated PBMCs) 
between pre-frail and frail participants (Exploratory Aim 3)
4. Two PAXgene® tubes (2.5 mL each, 5 mL total). These will be used to assess 
gene expression (i.e., mRNA). These will be rocked 10 times and allowed to sit 
at room temp for 2-24 hours. Then they will be frozen at -20°C and moved to -
80°C for long-term storage.
5. If we need to draw blood for a complete blood count (see below), we will draw 
one additional purple-top EDTA tube with 5 mL of blood.
If possible, we will obtain a complete blood count from a medical blood draw if the 
medical blood draw is conducted within the assessment week for T1 or T2. If there 
is no medical blood draw conducted within the appropriate assessment window for 
T1 or T2 then we will draw an additional 5 mL of blood (50 mL total) into a purple-


Protocol Date: January 20, 2023
32
top EDTA tube for a complete blood count with differential analysis for our 
research purposes.
Inflammation will be assessed using the latest available technology (e.g., in vitro 
enzyme-linked immunosorbent assay; ELISA). These assays will assess the 
concentration of inflammatory cytokines and receptors associated with frailty 
including TNF-α, TNFRI, TNFRII, CRP, IL-1β, and IL-8. Additional blood 
biomarkers of interest already available in the medical record will be obtained as 
well. All human biological materials will be disposed of in adherence with the 
University of Rochester Office of Environmental Safety Biosafety Level II 
requirements. All laboratories used in the current study have received appropriate 
biosafety certifications by the University of Rochester Institutional Biosafety 
Committee and undergo routine inspections. All samples will be de-identified 
before being stored.
The serum concentration of EGCG at the post-intervention time-point (T2) will be 
assessed using the latest available technology (e.g. ultra-performance liquid 
chromatography-tandem mass spectrometry (UPLC-MS/MS)) available by the 
URMC mass spectrometry resource lab.
Patient reported outcomes
Quality of Life (QoL): Functional Assessment of Cancer Therapy: Colorectal 
Cancer (FACT-C): To assess quality of life in patients with colorectal cancer. 
FACT-C is a 36-item assessment of domains of well-being: physical, social/family, 
emotional, and functional (specific to Colorectal cancer). Subjects are asked 
questions related to domains of well-being on a five-point scale (0-4) with 0 being 
a score of “not at all” and 4 being a score of “very much”. This questionnaire is a 
well-validated test for assessment of quality of life for patients with cancer 
receiving treatment. Patients who have colorectal cancer will complete this. 
Functional Assessment of Cancer Therapy: General (FACT-G): The FACT-G is a 
patient-reported outcome measure used to assess health-related quality of life in 
patients undergoing cancer therapy. Patients with any other cancer except colorectal 
cancer will complete the FACT-G.


Protocol Date: January 20, 2023
33
Symptom Burden: MD Anderson Symptom Inventory (MDASI): The MDASI is a 
13-item patient reported multi-symptom measure of symptoms found to have the 
highest frequency and/or severity in patients with cancer. It assesses symptom 
severity and symptom interference with daily life on a 1-10 scale. 
Physical Function: These tests are frequently conducted by our group and are safe with low 
risk.  
Short Physical Performance Battery (SPPB): The SPPB is an objective physical 
assessment evaluating lower extremity physical function.81 It is comprised of a 
three-meter walk (subject is asked to do this walk two times and the fastest time is 
used, so the total distance walked is six meters), repeated chair stands and a balance 
test. Impairment on SPPB testing has been shown to be predictive of short-term 
mortality and nursing home admission in community-dwelling older adults.
Timed-Up-And Go: The TUG measures, in seconds, the time taken by an individual 
to stand up from a standard arm chair, walk a distance of three meters, turn, walk 
back to the chair, and sit down for a total of six meters. The TUG is a measure of 
functional mobility that correlates to balance and fall risk. 
Yale Physical Activity Survey for Older Adults: This survey determined the type, 
amount, and patterning of physical activity/exercise in older adults. It is comprised 
of two sections. The first section assesses amount of physical activity/exercise 
performed during a typical week in the past month. The second section assesses the 
activities performed in the past month.
GODIN Leisure-Time Exercise Questionnaire: This short questionnaire is often 
used to assess leisure-time physical activity in oncology research. It is a 4-item self-
administered questionnaire with the first three questions asking about the number 
of times the patient engages in mind, moderate, and strenuous activities in sessions 
of at least 15 minutes in a typical week. This questionnaire is used to classify 
patients as active and insufficiently active according to the North American public 
health physical activity guidelines.
Epigenetic and proteomic differences


Protocol Date: January 20, 2023
34
Data specimen banking for future research. We will bank blood samples for use in 
future studies to assess epigenetic and proteomic profiles in pre-frail and frail 
subjects. We will also keep remaining samples for future research by Dr. Gilmore 
and her research team. The consent form includes a section asking whether subjects 
agree to have their samples banked for future studies by Dr. Gilmore and her 
research team.
5.6 Randomization
Randomization will be revealed to the subject at the end of the baseline assessment and 
immediately before delivering the study drug.
We will employ two arms in a 1:1 allocation ratio:
1. EGCG: 12 weeks daily of 800mg EGCG +250mg VitC taken 1 time a day at breakfast 
(four 200mg EGCG capsules will be packaged with one 250mg VitC tablet) 
2. Usual care
Consented subjects will be randomized with a computer-generated random numbers table with 
block sizes of 2. We will stratify by race (Black vs other) and treatment type (surgery vs other).
The random numbers tables will be generated centrally using software provided by Dr. Culakova, 
the project biostatistician. A total enrollment of 40 subjects is planned. Due to the study design the 
PI, study subjects, personnel, and statisticians will be un-blinded to the treatment assignments. 
5.7 Study Interventions (12 weeks’ duration)
Arm 1: EGCG: 800mg EGCG +250mg VitC taken 1 time a day. Subjects will a bag with 84 light 
resistant pill pouches. Each pill pouch will contain four 200mg EGCG capsules with one 250mg 
VitC tablet. Subjects will be instructed to take all the contents of each pill pouch every day at 
breakfast for a period of 12 weeks. Subjects will be monitored monthly for hepatotoxicity (liver 
function test of ALT, AST, and bilirubin). Subjects will receive a weekly phone call to assess any 
safety concerns and to assess adherence. 
Arm 2: Usual care – Subjects will be assigned to usual care during the course of the study. Subjects 
will receive a weekly phone call as a check in.


Protocol Date: January 20, 2023
35
5.8 Study Drug
Patients will be randomized to one of two treatment arms.  Encapsulated EGCG will be supplied 
by Teavigo. No subject identifiable data will be shared with Teavigo. Each capsule will contain 
on average 200mg EGCG (94%). Four 200mg EGCG capsules will be packaged with one 250mg 
VitC tablet and labelled at the pharmacy core at the University of Rochester Medical Center 
Investigational Drug Service (Dr. Steven Bean) into a light resistant pill pouch. At the time of 
randomization, study personnel will provide subjects with a bag with the 84 pill pouches, the 
twelve week supply of the study supplement. Instructions on how to correctly take the study drug 
will be given and reviewed with subjects in Arm 1. Subjects in Arm 1 will be instructed to start 
taking the study drug on day 1. The study drug will be stored in a secured location within the 
Cancer Control Unit at URMC that is locked at all times and only accessible by approved study 
personnel.  
5.9 Intervention contact and tracking
The study coordinator will make every effort to contact each subject 1 time per week via phone 
calls, and/or emails, (based on each subject’s preference) to encourage intervention adherence to 
the study drug. During this weekly contact the study coordinator will also ask about any safety 
concerns including: symptoms, signs, illnesses, or experiences, that develop or worsen during the 
study. These concerns will be graded (according to the CTCAE v5.0 see section 7), recorded, 
reviewed with the treating oncologist as well as the medical monitor, and reported (if necessary) 
according to the outline in section 7.  If medical information needs to be further discussed, we will 
set up a phone call, virtual meeting or face-to-face meeting. Study contact will occur from our 
research staff, which includes study PI, the study staff (coordinators, etc.), and the patient’s 
treatment team (e.g., oncologists, nurses, staff, etc.). 
Subjects in the intervention arm will report to URMC labs at weeks four and eight after baseline 
for a lab draw to determine liver function (ALT, AST, and bilirubin) so that any hepatotoxicity 
can be monitored. Study personnel will call subjects to remind and coordinate the blood draws. 
To track adherence, we will instruct subjects to bring all remaining study drug at their post-
intervention assessment (T2) and the pills will be manually counted and pill counts will be entered 
onto the pill excel document.


Protocol Date: January 20, 2023
36
5.10 Post-intervention assessment (T2)
The post-intervention assessment will follow the same format as the baseline assessment (T1) with 
the addition of Fried’s frailty measures from screening assessment (T0). In addition, we will also 
ask subjects to complete the following:
Secondary Aim 1: Pill count form
Subjects will be instructed to return any remaining study drug at their post-
intervention (T2) visit. All remaining study drug will be counted by research staff 
and pill counts will be used to determine adherence to study measures. 
Exploratory Aim 3: Semi-structured interviews: 
We will conduct semi-structured interviews with subjects at the post-intervention 
assessment (T2). Questions in the interview will be structured in a way to gained 
insights into the frailty experience of older survivors of colorectal cancer post 
adjuvant treatment. Interviews will be audio recorded and transcribed verbatim. 
Interviews with the subjects will be held in person in a private space (clinic or office 
space). Interviews will be audio-recorded and led by study investigators and will 
last 30 minutes. These recordings will be uploaded to Box, and the recordings will 
be deleted from the audio-recorder. All interviews will be transcribed and 
qualitatively analyzed in an iterative process until theoretical saturation is achieved.
We will also ask subjects about the usefulness and acceptability of the study treatments during the 
close out interview. The post intervention visit and measures may be completed in person, via 
phone and/or Zoom. 
5.11 Costs/Payments for participation
There will be no costs to the subject for assessments, screening tests, and parking. The subject will 
be responsible for travel to/from the research site, unless it is not possible for them to do so. If 
subjects are unable to obtain transportation for research appointments, we will attempt to arrange 
a car service at no cost to the subject (e.g., taxi, medicab, Uber, Lyft). Subjects will be compensated 
with a total of $60 for completing the study. Subjects in the usual care arm will be paid $30 for the 
completion of each assessment; T1 and T2. Subjects in the intervention arm will be paid $20 for 
the completion of each assessment; T1 and T2; and $10 for each hepatotoxicity blood draw a week 


Protocol Date: January 20, 2023
37
four and week 8 post-intervention. Payment will be in the form of pre-paid credit/debit card, gift 
card, or cash.
5.12 Return of research results
All data collected as part of this study will be for research purposes only and subjects will be 
explicitly told that the experiment will not provide information as to their health status. Study 
personnel will inform the subject’s clinical team is their scores on the cognitive test (MoCA) falls 
in the moderate range for cognitive impairment (≤19). 
6. SUBJECT WITHDRAWALS
Subjects may discontinue participation in the study at any time if they decide they do not wish to 
take part any longer. Subjects may be withdrawn from the study by research personnel if it is 
deemed in their best interest to no longer participate or in the case of lack of cooperation, non-
compliance, or other administrative reasons. If a subject withdraws from the study, the information 
they have already provided will be kept in a confidential manner.
7. REPORTABLE EVENTS
 An adverse event (AE) is any symptom, sign, illness, or experience that develops or worsens 
during the study, whether or not the event is considered related to the intervention. To assess the 
severity of adverse events, we will use the Common Terminology Criteria for Adverse Events 
(CTCAE) 
v5.0, 
recommended 
by 
the 
NCI. 
The 
CTCAE 
is 
available 
at 
http://ctep.cancer.gov/reporting/ctc.html. The CTCAE displays Grades 1 through 5 with unique 
clinical descriptions of severity for each adverse event based on this general guideline:

Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.


Protocol Date: January 20, 2023
38

Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL).

Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL.

Grade 4: Life-threatening consequences; urgent intervention indicated.

Grade 5: Death related to adverse event.
A serious adverse event (SAE) is any adverse medical experience that results in death, or is life-
threatening, or requires inpatient hospitalization of at least 24 hours, or prolongs existing 
hospitalization, or results in persistent or significant disability/incapacity, or causes a congenital 
anomaly/birth defect, or requires medical or surgical intervention to prevent permanent 
impairment or damage.
Stopping Criteria: If disease progresses while on study and participant must restart cancer 
treatment, and participant is in the Intervention arm, participant will stop taking the study drug. 
Participant will still complete study measures. If disease progresses while on study and participant 
must restart cancer treatment, and participant is in the Usual Care arm, participant will still 
complete study measures. Any subject in the intervention arm with unexplained Grade ≥ 2 ALT, 
AST, or bilirubin increase will stop taking the study drug. 
If a drug-related Grade≥ 3 hepatotoxicity is observed in any subject in the intervention arm the 
study will be stopped.  (See Section 11.3 for more information)
Attribution: An assessment of the relationship between the adverse event and study intervention, 
using the following categories.
ATTRIBUTION
DESCRIPTION
Unrelated
The AE is clearly NOT related to the intervention
Unlikely
The AE is doubtfully related to the intervention
Possible
The AE maybe related to the intervention
Probably
The AE is likely related to the intervention
Definite
The AE is clearly related to the intervention


Protocol Date: January 20, 2023
39
The subject’s referring oncologist, designee, or study medical monitor will determine the grade 
and attribution.
With that information, we will only report the following events:

Grade 3, 4, or 5 events that are possibly or probably related to the study intervention will 
be reported to the Data Safety Monitoring Committee and the Research Subjects Review 
Board (RSRB) at each continuing review. 

Serious, related, and unexpected events will be reported to the RSRB in an expedited 
manner.

We will also maintain a record of these reportable events.
8. RISK/BENEFIT ASSESSMENT
8.1 Risks to subjects
There are four potential risks associated with participation in the proposed study
1. Physical harm associated with assessment procedures
2. Physical harm associated with intervention procedures
3. Emotional distress
4. Loss of confidentiality through email communication
1. In terms of physical harm associated with assessment procedures, risks associated with 
some of the physical tests are minimal. They include minimal risk of falling when completing 
physical function measures (Timed-Up-and-GO and Short Physical Performance Battery).
2. In terms of physical harm associated with intervention procedures, there are few known 
and possible interactions of EGCG with other drugs. A few possible herb-drug interactions have 
been reported in a variety of disease settings and animal models. These include possible 
interactions with adenosine, anticoagulants/antiplatelets, codeine, bortezomib, tamoxifen, 
verapamil, 
irinotecan, 
cytochrome 
p450 
34 
substrates, 
uridine 
5’-diphospho-
glucuronosyltransferase substrates, acetaminophen, nadolol, and palbociclib.82-94 These 
interactions are possible due to an interaction with EGCG itself or other components within green 


Protocol Date: January 20, 2023
40
tea, e.g. tannin.95 This product is caffeine free so sleep disruption is not anticipated. There is also 
a risk of hepatotoxicity associated with the consumption of EGCG.
3. In terms of emotional distress, some subjects might be distressed at their performance in some 
of the GA measures. Some measures e.g. the geriatric depression scale contains sensitive 
questions. Subjects are not required to answer any questions for any reason. 
4. In terms of loss of confidentiality, both quantitative data and biological samples from subjects 
will need to be stored. Thorough, rigorous, and well-tested data safety and security guidelines will 
be observed, there is still a chance that confidentiality could be breached and sensitive medical 
information could become known to persons outside the research team. There is also a small 
chance that a subject’s identity could be revealed if our secure data servers are broken into.
8.2 Adequacy of protection against risk
We will protect against all study risks, which are:
1. Physical harm associated with assessment and intervention procedures
2. Emotional distress
3. Loss of confidentiality
1. Physical harm associated with assessment and intervention procedures: 
Every effort will be made to minimize the risks associated with study procedures for all 
subjects. First, all subjects must have the approval of their physician to enter the study. 
Research personnel will assess patient’s ability to conduct any of the physical assessments 
before patient’s attempt. Physical tests will only be performed is it is safe to do so. When 
a subject is completing any of the physical tests, the research personnel will stay behind 
and to the side of the subject to assist in the case the subject loses balance or begins to fall. 
When using chairs, the chairs will be positions so they do not move (e.g. chair’s back will 
be placed against the wall).
2. Emotional distress: 
To prevent distress, subjects will be informed that they are free to decline to answer any 
question for any reason. Research staff will be extensively trained to help minimize distress 
to subjects. However, should subjects become depressed, anxious, agitated, or otherwise 
distressed during the assessment, a trained member of the research staff will be notified 


Protocol Date: January 20, 2023
41
and the subject will be triaged and referred for care. Should the subject already be receiving 
care, they will be referred to follow up with their care provider and a check in call will be 
made following the assessment to establish subject safety and comfort.
4. Confidentiality: 
This study involves collecting biological samples, data from clinical and self-reported 
assessments, obtaining access to medical records, and communicating via email. Thus, 
steps must be taken to protect both subject data and identity. The following confidentiality 
protection steps will be taken:
1. Research staff will participate in initial training, follow-up training, and ongoing 
monitoring and supervision to ensure understanding of the ethical issues involved in 
this research. Training will be provided in accordance with URMC policies (e.g., online 
coursework via the CITI collaborative, ongoing discussions with senior scientific 
colleagues).
2. Only the research staff will know the name, identification (ID) number, and contact 
information of subjects. The list that links the subject’s name with ID number will be 
kept on an encrypted drive accessible only by the research staff.
3. Consent forms will be kept in locked filing cabinets in a locked office, again accessible 
only by research staff.
4. Any personal identifiers linked to data will be removed and replaced by non-identifying 
ID numbers in all records. The electronic files that contain quantitative data will be 
stored on a secure University of Rochester Medical Center file server. These files will 
be password-protected and accessible only by the study staff.
5. The risk of email communication is included in our Consent Form.
6. While first names will be used in individual interviews in order to facilitate discussion 
and comfort with the research interviewer, all personal identifiers will be deleted (e.g. 
de-identified) from the transcriptions of the audio-recordings. All study data will be 
stored in locked cabinets and electronic files will be stored using HIPPAA-compliant 
storage solutions. Audio recorded data will be kept for approximately 5 years.


Protocol Date: January 20, 2023
42
8.3 Benefits
There may or may not be any direct benefits of the study to the study subjects. The potential benefit 
to the subject from being in this study might be receiving the results from some of the tests, 
possibly enabling better insight and awareness into the subjects’ health.    
8.4 Alternatives to participation
The subject may choose to not participate in the study without penalty or effects on subsequent 
medical care, etc.
9. CONFIDENTIALITY OF DATA AND DATA STORAGE
9.1 Utilizing Research Electronic Data Capture (REDCap)
Study data will be collected via paper forms then study personnel will electronically enter 
participant data into a web-based survey administered using REDCap software. REDCap is a 
secure, web-based application for building and managing online surveys and databases and is made 
available through the University of Rochester Clinical and Translational Science Institute. 
REDCap will be used to send a secured web link to each study subject, and a built-in scheduling 
function will allow for re-contact at a pre-specified time to remind subjects to assessments if 
needed. All data forms will be checked immediately by the REDCap system as they are being 
completed by the study personnel to ensure completeness (i.e., that no question was skipped 
unintentionally), and a pop-up message feature will be used to encourage a response. Once data 
collection is complete, REDCap provides an automated export procedure for data download. Every 
effort will be made to reduce attrition and obtain follow-up data. Steps will be taken to avoid 
missing data. If subjects do not complete surveys after receiving a follow-up reminder, the study 
coordinator will attempt to contact the subject via phone and ask if they are willing to give their 
responses verbally for the study staff member to enter into the REDCap database.
9.2 Data storage
All hardcopy research records will be stored onsite in the University of Rochester Medical Center 
and in the Cancer Control. The Cancer Control Unit is located in the Saunders Research Building, 


Protocol Date: January 20, 2023
43
in an office suite secured by electronic key cards. Electronic research records are stored on the 
University of Rochester Medical Center’s password secured and firewall protected networks. 
These are the same methods of security used for subject medical records. Human serum samples 
are stored in locked freezers, within secured areas of the Medical Center that are accessible by key 
codes and electronic card swipes.
All study data will be kept for a period of at least six years after the study and all reports and 
publications are complete.
9.3 Human blood samples
All data (information and human blood samples) collected for the current study will be used in 
post hoc analyses as appropriate. Blood samples will be banked and data will be used for future 
studies only with prior consent of subjects. The consent form contains appropriate language related 
to banking and subjects are given the option to have their samples banked or to have them 
destroyed following analysis of the study hypotheses. Subjects’ individual research records will 
not be shared with their treating physician, unless they provide consent or the subject’s treating 
physician is a study physician, in which case they will have access to study data as a study co-
investigator. Overall study results may be presented to subjects, faculty and staff at the University 
of Rochester Medical Center after completion of the study. Study results will be presented at 
professional meetings, published, and reported on clinicaltrials.gov.
9.4 Assignment of study ID
The study team will assign a numerical Study ID to each subject once they have signed the consent 
form. Study forms and questionnaires will use this number and the subject’s first and last initials 
as identifiers to ensure data integrity. Other identifying information will not exist on these forms. 
A complete list of study subjects with study ID, name, and contact information will be maintained 
separately for the purpose of contacting subjects for phone call or e-mail reminders; this database 
will be maintained until at least six years after the study is complete. This linkage information will 
only be accessible to the study chair, study investigators, and the individual responsible for 
maintaining the database.


Protocol Date: January 20, 2023
44
10. RESEARCH INFORMATION IN MEDICAL RECORDS
Documentation of study participation will be included in the medical record by means of uploading 
a signed consent form to each subject’s medical record. Subjects’ blood draw will also be noted in 
the medical record. For the duration that patients are on-study (13 weeks) their electronic records 
will indicate their active participation. After study participation is complete, this indication will be 
removed. No further research-related information will be included in the medical record.
11. DATA ANALYSIS AND DATA MONITORING
11.1 Sample size determination
We plan to enroll 40 subjects (20; ≥6 AA/B per 
arm). Evaluation of recruitment and adherence 
to the intervention is required for planned future 
Phase 2/3 frailty trials in older cancer survivors. 
Aim 1: With a feasibility target of 70% of 
Figure 5: Sample Size Calculation


Protocol Date: January 20, 2023
45
randomized subjects completing the study  we expect at least 14 evaluable patients per arm, which 
is appropriate for small randomized studies96 and it will allow us to obtain preliminary estimates 
of descriptive statistics (mean, standard deviation (SD), and confidence intervals (CI)). Aim 2: At 
significance level α=0.15, N=14 per arm will provide 70% power to detect effect size (standardized 
mean change in frailty score) of 0.66, if pre-post correlation=0.5 (conservative estimate for FFS; 
Figure 5). 
Analyses: Aim 1: For each feasibility outcome (recruitment and adherence), we will evaluate 
proportions of subjects meeting criterion and report percentages with CIs.  For AEs, we will report 
the total and severity of AE’s per group. Aim 2: Descriptive statistics will be calculated at baseline, 
post-intervention, and for pre-post change scores for subjects in EGCG and UC arms. To evaluate 
the preliminary efficacy estimates of EGCG on FFS we will use an analysis of covariance 
(ANCOVA) model (outcome=FFS at post, covariates: FFS at baseline and arm). Estimates of 
distribution characteristics (e.g., mean, variance, pre-post correlation) and preliminary estimates 
of efficacy will inform the design and sample size of our planned future study. Aim 3: Similar 
analyses to Aim 2 will be performed for TNF-α, TNFRI, TNFRII, IL-6, IL-1β, and CRP. If data 
for inflammatory markers are missing due to lower limit of detection, we will use appropriate 
imputation methods.97,98 Aim 4: Using similar analyses to Aim 2, we will conduct preliminary 
subgroup analyses by race and treatment type.
11.2 Statistical analysis
Quality control. We will use electronic forms and audit our database. We will visually inspect all 
data. The distribution of the data will be examined. If deviations from statistical assumptions are 
detected, appropriate statistical steps (e.g., transformation, non-parametric analysis, missing data 
sensitivity analysis) will be applied. To follow the "intent-to-treat" principle, patients will be 
analyzed according to randomization. Since this is a small feasibility trial, study hypotheses will 
be tested at α=0.15 (2-tailed significance level).99 We will work closely with Dr. Culakova 
(biostatistician).
Missing data. Every effort will be made to facilitate the subjects' completion of questionnaires and 
comprehensive collection of data.100 If there are missing data, reasons for missing data will be 
recorded, tabulated and reported based on treatment group. Differences in patterns of missing data 


Protocol Date: January 20, 2023
46
between treatment groups will be compared. Special considerations will be given to missing data 
for inflammatory biomarkers. If inflammatory biomarker data are missing due to lower limit of 
detection, we will use the appropriate imputation method.97,98 Otherwise, since this is a small 
study, we will report the complete case analysis. We will use the information about missing data 
when assessing feasibility.
11.3 Data and Safety Monitoring Plan
The subject’s physician will determine if the adverse event requires expedited review.
The James P. Wilmot Cancer Center Data Safety Monitoring Committee (DSMC) will serve as 
the DSMC of record for this study. The DSMC provides oversight of study progress and safety by 
review of accrual and events at regularly scheduled meetings. The frequency of review is 
determined by the size, risk and complexity of the trial, and has been assigned by the Cancer 
Center’s Peer Review Committee at the time of their review and approval of each protocol.
The study PI will conduct continuous review of data and subject safety. The Investigator will 
submit (semiannual, annual) progress reports of these data to the DSMC for review. The review 
will include the number of subjects enrolled, withdrawals, significant toxicities as described in the 
protocol, and serious adverse events (both expected and unexpected). The Investigator will submit 
a copy of the AE spreadsheet along with the Progress Report to the DSMC for review. Actual 
review dates will be assigned when the first subject is accrued.
Any serious adverse event that is serious, related, and unexpected will be reported within 10 
calendar days to both the Safety Coordinator and the RSRB. The DSMC Chair will determine 
whether further action is required, and when subject safety is of concern. When subject safety is 
of concern, an interim meeting may be called.
Serious adverse events that are related (either expected or unexpected) will be reported to the 
Committee for review at the quarterly meeting. SAE reports are expected to include enough detail 
so that the DSMC can determine the severity, toxicity grade, expectedness, treatment required, and 
a follow-up report documenting resolution of if there are sequelae. See section 7. REPORTABLE 
EVENTS for specific reporting requirements for this protocol.


Protocol Date: January 20, 2023
47
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