Physical Training for Elderly Cancer Patients With Cachexia (TEECH-01): a Prospective Clinical Trial
Phase: NA
Conditions: Geriatric Assessment, Cancer, Cancer Cachexia
Sponsor: National Cheng-Kung University Hospital

 
1 
 
Cover Page 
 
Title: 
Physical Training for Elderly Cancer Patients with 
Cachexia (TEECH-01): a Prospective Clinical Trial 
 
NCT ID: 
To be determined 
 
Document date: 
To be determined 
 
Version 4.0 07/Apr/2023 
Version 5.0 01/Jun/2023 
 
 
 

 
2 
 
Abstract 
Background 
Elderly cancer patients present with high comorbidities and adverse outcomes. 
Of note, those with cancer cachexia share an even worse result. Physical 
exercise improves the functional wellbeing and alleviates symptoms in patients 
with cancer cachexia. However, such interventions have not been explored in 
elderly cancer patients with cachexia. 
Objectives 
The proposed trial is to investigate the feasibility and efficacy of an artificial 
intelligence-based patient-tailored intensity-modulated physical training for 
cancer patients aged over 65 at risk of cancer cachexia. The primary endpoint 
is simplified cancer CAchexia SCOre (MiniCASCO) reduction. Secondary 
endpoints include geriatric assessment, physical activity and sarcopenia. 
Study design and accrual 
This is an open-label, single-arm, single-center phase II investigator-initiated 
trial. We assume a reduction of MiniCASCO by 10% after trial intervention. 
Under a statistical power of 80% and a probability of type I error at 0.1 (two-
tailed), a minimal of 49 subjects will be enrolled. 
Treatment protocol 
All subjects will receive a 12-week supervised physical training and nutritional 
intervention. Efficacy assessments will be conducted at baseline (week 0), post-
intervention (week 12) and follow-up period (week 24). 
Anticipated results 
An optimal patient-tailored training program is feasible and improves the 
symptoms and severity of elderly cancer cachexia. The results may shed light 
on the debilitating and burdensome condition and provide information on 
future clinical trials. 
 
 
 
 

 
3 
 
SYNOPSIS 
Title of the 
study: 
Physical Training for EldErly Cancer Patients with 
CacHexia (TEECH-01): a Prospective Clinical Trial 
Intervention 
provider: 
SeniorGym, Medical Device Innovation Center (MDIC), 
National Cheng Kung University Hospital, College of 
Medicine, National Cheng Kung University, Tainan, Taiwan 
Address: MDIC, No.1, University Road, Tainan City 701, Taiwan 
(R.O.C) 
Tel: 886-06-236-3157 
E-mail: em73421@email.ncku.edu.tw 
Objectives: 
The objective of the study is to evaluate a patient-tailored 
physical training program in elderly cancer patients who 
have risk of cachexia. 
Primary outcome: at week 12 
▪ Simplified cancer CAchexia SCOre (MiniCASCO) 
reduction. 
Secondary outcome: at week 12 
▪ Geriatric assessment scales 
▪ Physical activity (hand grip strength, gait speed, body 
mass index (BMI), sit to stand (STS), back stretch, sit reach, 
single leg stand (SLS), up and go (UG), 2-minute step 
(2MS), 6-minute walk test (6MWT) and timed up-and-go 
(TUG) 
▪ Sarcopenia score (SARC-CALF) 
Exploratory outcome: 
Health-related quality of life (HRQoL), cancer-related 
survival, recurrence/progression, cancer treatment or 
study intervention-related adverse events, nutritional 
scales and Zebris gait analysis 
Design: 
The proposed study is an open-label, single-arm, single-
country and single-center phase II investigator-initiated 
trial. 
Sample size: 
We assume the statistical power of 80% (β=0.2) and the 
probability of type I error by two-tailed α at 0.1, along with 
a reduction of MiniCASCO by 10% from baseline at week 12. 
A total of 49 subjects will be enrolled. 
The trial contains two parts: 
Part I: 10 subjects as a safety run-in and eligibility cohort 

 
4 
 
Part II: 39 subjects as a complete cohort 
Criteria for 
inclusion: 
1. Subjects aged equivalent to or over 65 years with an 
existing cancer requiring antineoplastic treatments at trial 
enrollment, as defined by presence of a catastrophic disease 
certificate for malignancy in National Health Insurance 
(NHI)-Taiwan. 
2. Subjects receive at least one systemic antineoplastic 
treatment within 12 weeks since trial enrollment, which 
includes 
chemotherapy, 
immunotherapy, 
hormonal, 
targeted and cellular therapy of whichever initial 
therapeutic intent (curative, palliative or salvage). 
3. Subjects fulfill either cancer cachexia or pre-cachexia. 
3.1. Cancer cachexia:  
A maximal weight loss of at least 5% from the baseline 
within 6 months in those whose BMI equivalent to or over 
20 kg/m2 or at least 2% in those whose BMI less than 20 
kg/m2.  
3.2. Pre-cachexia:  
A maximal weight loss of 1% to 5% from the baseline within 
6 months in patients whose BMI equivalent to or over 20 
kg/m2 or 1% to 2% in those whose BMI less than 20 kg/m2 
plus any of the following: an elevated serum C-reactive 
protein above upper normal limits (ULN), impaired fasting 
glucose or known diabetes mellitus, use of high-dose 
corticosteroid (over 10 mg prednisone equivalent daily), 
hypogonadism 
(disease-related 
or 
iatrogenic) 
or 
insufficient calorie intake of less than 20 kcal/kg/day 
4. Subjects are in a clinical status with an expected life span 
exceeding 6 months and Eastern Cooperative Oncology 
Group (ECOG) 0 to 1 or Karnofsky Performance Scale (KPS) 
80 to 100 at trial enrollment. 
5. Subjects are physically and mentally capable and willing 
for conducting the planned physical training and agreed to 
comply the educational instructions and a wearable device 
during trial intervention. 
6. Subjects are functionally and cognitively capable to be 
informed of the trial contents and objectives (including 
obtaining peripheral blood sampling for trial investigation), 

 
5 
 
and agree to sign the written consent for enrollment. 
Criteria for 
exclusion: 
1. Subjects have tumor in situ or curatively treated 
malignant disease which requires no further antineoplastic 
treatments. 
2. Subjects are anticipated to receive any surgery, 
radiotherapy or intervention that prevents or hinders a 
planned physical training within 28 weeks since trial 
enrollment. 
3. Subjects experience a progressive body weight loss which 
fulfills the criteria for cancer cachexia or pre-cachexia but 
complicates with other confounding causes. (please refer to 
5.2.3.1. to 5.2.3.4.) 
4. Subjects have cachexia caused by etiologies not limited to 
cancer. (please refer to 5.2.4.1. to 5.2.4.3) 
5. Subject’s malignant disease is considered unstable and 
thereby unfit for a planned physical training. (please refer 
to 5.2.5.1. to 5.2.5.4.) 
6. Subjects have an underlying medical illness causing 
severely impaired organ functions. (please refer to 5.2.6.1. 
to 5.2.6.5.) 
7. Subjects have an active infection requiring hospitalized 
treatment or intravenous anti-pathogen therapies. 
8. Subjects who receive other experimental treatments or 
interventions for cancer cachexia. 
9. Subjects are planning to conceive or already in 
pregnancy. 
10. Subjects are currently participating in any other 
observational studies concerning cancer cachexia. 
Protocol 
intervention: 
1. Supervised Physical Training in SeniorGym 
a. Aerobic exercise for 12 weeks 
Patient-tailored intensity-modulated ergometer training 
for the limbs 
--Target intensity: moderate 
--Frequency: 2 to 3 sessions per week 
--Duration: 8 to 25 minutes per session 
b. Resistance exercise for 12 weeks 
Patient-tailored resistance exercise by Theraband® for the 
limbs 

 
6 
 
--Target resistance: moderate 
--Frequency: 2 to 3 sessions per week 
--Duration: 20 minutes per session 
2. Nutrition intervention 
--Dietician consultation and education at 0, 12 and 24 
weeks 
--Nutrition intervention at 0, 12 and 24 weeks 
 
TRIAL SCHEMA 
Physical Training for Elderly Cancer Patients with Cachexia (TEECH-01): a 
prospective clinical trial 
 
Primary endpoint: MiniCASCO reduction at week 12 
 
 
 

 
7 
 
TABLE OF CONTENT 
 
1. OBJECTIVES∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙1 
2. BACKGROUNDS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙1 
3. STUDY INTERVENTION INFORMATION∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙4 
3.1 Aerobic exercise∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙4 
3.2 Resistance exercise∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙5 
3.3 Nutrition assessment∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙6 
4. DISEASE SEVERITY CRITERIA AND TOOLS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙6 
5. PATIENT SELECTION∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙7 
6. STUDY DESIGN AND TREATMENT PLANS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙9 
7. STUDY SCHEDULE∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙12 
8. EVALUATION OF INTERVENTION EFFICACY∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙15 
9. STATISTICAL CONSIDERATION∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙19 
10. REPORTING OF SEVERE ADVERSE EVENTS TO INSTITUTIONAL 
REVIEW BOARD (IRB) OF ETHICS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙19 
11. OTHERS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙20 
12. REFERENCES∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙20 
 

 
1 
 
1. OBJECTIVES 
 
1.1 Objective of the study:  
To investigate the feasibility and efficacy of an artificial intelligence (AI)-based 
patient-tailored intensity-modulated physical training program for elderly 
cancer patients at risk of cancer cachexia. 
 
1.2 Primary objective: 
Simplified cancer CAchexia SCOre (MiniCASCO) reduction. 
 
1.3 Secondary objectives: 
Geriatric assessment scales, physical activity (hand grip strength, gait speed, 
body mass index (BMI), sit to stand (STS), back stretch, sit reach, single leg 
stand (SLS), up and go (UG), 2-minute step (2MS), 6-minute walk test (6MWT) 
and timed up-and-go (TUG)), sarcopenia score (SARC-CALF), health-related 
quality of life (HRQoL), cancer-related survival, recurrence/progression, 
cancer treatment or study intervention-related adverse events, nutritional 
scales and Zebris gait analysis 
 
 
2. BACKGROUNDS 
Aging and Cancer Care 
Aging has become a tremendous health-related issue worldwide in both 
developing and developed countries.1 Aging and super-aging cause various 
consequences such as physiological alterations, impaired organ function, 
progressing disability, poor nutrition and comorbidities, and therefore 
transform the fit population into unfit ones.2 Numerous assessment methods 
have emerged to cope with risk prediction and allocation in the diseased elderly, 
such as Geriatric 8 (G8), Groningen Frailty Indicator, Vulnerable Elders Survey 
13 and abbreviated geriatric assessment (aCGA).3 Elderly cancer patients are 
particularly vulnerable with an increased risk of complications and morbidities. 
In elderly cancer patients who would receive antineoplastic therapies, 
Chemotherapy Risk Assessment Scale for High-Aged Patients (CRASH) and 
Cancer and Aging Research Group (CARG) scale were developed to weigh the 
balance between treatment toxicity and benefit in those aged over 60.4,5 
However, such tools are only applied to selected fit elderly population and not 
robustly validated to those aged over 65. Of note, Sleeman et al. reported cancer 
related deaths or disability increased by 87% with an annual increment of 26 

 
2 
 
million people worldwide.6 Aside from geriatric assessments, there are scarce 
interventions aimed at elderly cancer patients, in which it presents with a huge 
health-related burden in cancer care. 
 
Geriatric Cancer Cachexia 
Cancer cachexia, as featured by progressive body weight loss (BWL) and/or 
skeletal muscle mass depletion, is found in 50% to 80% of cancer patients and 
accounts for 20% of cancer-related deaths.7-9 Confounded by inconsistent 
definitions, cancer cachexia shares undetermined characteristics in different 
types of cancer patients. However, growing efforts have reached an 
international consensus defining cancer cachexia by progressive BWL over 5% 
within 6 months plus several metabolic changes. The severity was also staged 
by pre-cachexia, cachexia and refractory cachexia, respectively.8 Dunne et al. 
indicated that 80% of elderly cancer patients who had cachexia presented with 
prominent BWL within 6 months.10 Poisson et al. further investigated the 
prevalence and severity of geriatric cancer cachexia in the French nationwide 
study and concluded that nearly half of the elderly cancer patients harbored 
cachexia, which correlated with 6-month mortality.11  
 
With the discovery on its comprehensive biological and physiological impacts, 
Argilés et al. proposed and validated a cancer cachexia scoring system (CASCO) 
which contained parameters and assessments on various aspects.12 A simplified 
form of CASCO (MiniCASCO) was also developed to enhance the clinical 
application and accessibility while maintaining a high correlation with the 
original version.13 Both CASCO and MiniCASCO encompassed multifaceted 
parameters, such as weight loss, lean body mass, serum biochemical markers, 
physical performance, anorexia, and health-related quality of life (HRQoL). 
Interestingly, elderly patients are known especially vulnerable and suffer from 
cancer cachexia with progressive frailty, deconditioning and intolerability to 
antineoplastic treatments.14 The phenomenon of failure to thrive in geriatric 
cancer patients is often multifactorial and responds poorly to conventional 
nutritional support or interventions.15 However, little is known about the 
application of cachexic scores in elderly cancer patients. In addition, studies 
concerning interventional measures to improve cancer cachexia in the elderly 
population is extremely rare. 
 
Physical Training for Elderly Cancer Patients 
Physical activity and exercise capacity are vital components of fitness and help 

 
3 
 
reduce mortality and improve HRQoL in cancer patients.16 Maintaining 
physical activity is considered a treatment discrepancy between elderly and 
younger patients with cancer.17 Emerging studies have confirmed that physical 
training attenuated and partially reversed muscle wasting by modulating 
metabolic, protein degradation and inflammatory pathways.18,19 In addition, 
several studies have implemented exercise-based interventions to improve the 
physical capacity, HRQoL and outcomes of elderly patients with cancer.20-24 
Mikkelsen et al. showed a 12-week exercise program increased lean body mass 
in elderly cancer patients, which provided a rationale for physical training in 
the patient population with potential cachexia.25 Furthermore, the advantages 
of appropriate physical training are not limited to improve physical activity 
alone. It might extend to enhance muscle strength, nutritional absorption, 
cognitive function, emotional fitness and even ameliorate cancer-related 
symptoms.26,27 However, considering the putatively frail and weak conditions 
imposed by disease activity and ongoing antineoplastic treatments, an 
intensity-modulated patient-tailored exercise intervention is required to 
increase the feasibility and tolerability in elderly cancer patients at risk of 
cancer cachexia. 
 
Study Rationale and Aim of Trial 
Physical training and patient-tailored exercise improve the clinical outcome of 
elderly cancer patients. In addition, growing evidence suggests that optimal 
physical training ameliorates the negative impacts on cancer cachexia in 
patients with cancer. However, only limited reports have focused on patient-
tailored physical training in elderly cancer patients at risk of cancer cachexia. 
Given the paucity of studies on this issue, it prompts an investigation of 
potential pluripotent effects of physical training in patients with both elderly 
cancer and cachexia. Furthermore, an optimal model for designing an 
appropriate training program remains undetermined.  
 
Therefore, the proposed clinical trial is a single-arm, prospective interventional 
study investigating a patient-tailored physical training program for elderly 
cancer patients at risk of cachexia. The aim of the proposed trial is to study the 
feasibility of an artificial intelligence (AI)-based patient-tailored physical 
training program which could be applied to elderly cancer patients at risk of 
developing cancer cachexia. We hypothesize that the optimal AI-modulated 
patient-tailored program is feasible to be implemented in the clinical practice 
and improves the symptoms and severity of elderly cancer cachexia post 

 
4 
 
intervention. In summary, we hope the results of the proposed trial shed light 
on the debilitating and burdensome condition and provide information on 
designing future phase III clinical trials. 
 
 
3. STUDY INTERVENTION INFORMATION 
 
3.1 Aerobic exercise:  
3.1.1 Contents: 
In the aerobic exercise program, an AI-based intensity-modulated supervised 
physical training is provided to the subjects in the SeniorGym, MDIC, National 
Cheng Kung University Hospital. The training module is composed of feedback 
assistive ergometer of lower limbs, as judged by the investigator or subject’s 
preferences and their physical capacity. The infrastructure of training includes 
strengthening 
of 
limb 
muscles, 
resistance, 
aerobic 
activity 
and 
cardiopulmonary rehabilitation. An interactive program is provided during the 
training session, which consists of a first-person perspective video game 
intended to collect coins on a mountain trail. Meanwhile, automated positive 
feedbacks with visual or sound clues are presented to enhance the participating 
motives of the subject. At the end of each training session, the cumulative 
intensity, calorie consumption and energy expenditure are shown as a grading 
score to the subject. A specialized physical trainer or study nurse will act as a 
supervisor and accompany the subject throughout the entire training session 
and being responsible for monitoring the training performance and 
maintaining safety precautions. 
 
3.1.2 Training target: 
During each of the session, the maximal intensity is determined by a moderate 
intensity of aerobic exercise, reaching 80% of maximal predicted heart rate 
(mpHR = 208 −0.7 × age of the subject; beats per minute (bpm))28, subjective 
maximal physical tolerance or discomforts, investigator or supervisor-decided 
adequate level of training and onset of any alarming feedbacks on the 
biophysical detectors, including subnormal readings on heart rate (>180 or <60 
bpm), blood pressure (systolic blood pressure (SBP) >160 or <90 mmHg) or 
pulse oximetry (SpO2<88% with ambient air), in whichever achieves first. Each 
session lasts 8 to 25 minutes with a gradual increment of both resistance and 
duration along the training process. Two to three sessions per week will be 
arranged with a minimal interval of 24 hours between two consecutive sessions. 

 
5 
 
A total of 12-week training is provided to each subject when tolerated. 
 
3.1.3 Safety information: 
All sessions will be supervised and monitored by specialized physical trainers 
or study nurses in the trial. Emergent withdrawal or discontinuation of an 
ongoing training session is determined by any the following conditions: 1) onset 
of any abnormal readings on the biophysical detectors, including HR >200 or 
<45 bpm, SBP >180 or <85 mmHg or SpO2<85%; 2) subjective discomforts, 
failure to comply or demands for stopping upon reasonable request; 3) 
supervisor’s professional judgment and discretion; 4) signs or symptoms 
suggestive of risk of physical trauma or injury. All alarming events will be 
recorded and presented to the principal investigator as safety monitoring 
references. 
 
3.2 Resistance training:  
3.2.1 Contents: 
In the resistance exercise program, a trainer-assisted supervised manual 
physical training is provided to the subjects in the SeniorGym, MDIC, National 
Cheng Kung University Hospital. The training module is composed of utilizing 
Therabands® to conduct limb or trunk stretching under fair resistance. The size 
of Therabands® can be switched from light, moderate to heavy ones according 
to training requirement of the subject. Subjects are educated about the proper 
use of Therabands® and encouraged to demonstrate resistance training at 
home freely without a supervisor. 
 
3.2.2 Training target: 
Each session lasts 20 minutes with a gradual increment on resistance along the 
training process. Two sessions per week will be arranged with a minimal 
interval of 24 hours between two consecutive sessions. A total of 12-week 
training is provided to each subject when tolerated. 
 
3.2.3 Safety information: 
All sessions will be supervised and monitored by specialized physical trainers 
or study nurses in the trial. Emergent withdrawal or discontinuation of an 
ongoing training session is determined by any the following conditions: 1) onset 
of any abnormal readings on the biophysical detectors, including HR >200 or 
<45 bpm, SBP >180 or <85 mmHg or SpO2<85%; 2) subjective discomforts, 
failure to comply or demands for stopping upon reasonable request; 3) 

 
6 
 
supervisor’s professional judgment and discretion; 4) signs or symptoms 
suggestive of risk of physical trauma or injury. All alarming events will be 
recorded and presented to the principal investigator as safety monitoring 
references. 
 
3.3 Nutrition assessment and intervention:  
3.3.1 Contents: 
In the nutrition assessment and intervention program, a specialized dietician 
will be responsible for calculating and analyzing the daily calorie requirement 
and food composition of the subject in the specialized dietary outpatient clinic. 
A professional diet consultation and nutritional recommendations will be 
provided upon willingness of the subject. Dietary prescriptions will be adjusted 
according to subject’s food preferences, underlying illness, food allergy and 
cost-effectiveness. In addition, subjects are educated and encouraged to record 
all the ingested food as a dietary diary and presented to the dietician when 
visited. 
 
3.3.2 Intervention target: 
During dietary and nutrition consultation, the calorie intake is adjusted to a 
target of 25 to 30 kcal/kg/day. Forty to fifty percent of the daily calorie is 
expected to derive from carbohydrate source. Protein ingestion, as either from 
animal or vegetarian sources, is aimed at 1.2 g/kg/day at least. Given that 
subjects may fail to achieve the target calorie dose, the actual maximal calorie 
intakes are recorded and compared with the prespecified targets. 
 
3.2.3 Safety information: 
Since the nutrition assessment and intervention are advisory and educational, 
there are no safety warnings of the session. 
 
 
4. DISEASE SEVERITY CRITERIA AND TOOLS 
Cancer cachexia or pre-cachexia of the elderly in the trial is defined according to 
Fearon et al. and analyzed collectively.8 The disease severity is defined by 
MiniCASCO from 0 to 100 points. The grading of cancer cachexia is followed by 
minimal (0 to 14), mild (15 to 28), moderate (29 to 46) and severe cachexia (47 to 
100), respectively.17 
 
 

 
7 
 
5. PATIENT SELECTION 
 
5.1 Inclusion criteria 
5.1.1. Subjects aged equivalent to or over 65 years with an existing cancer 
requiring antineoplastic treatments at trial enrollment, as defined by presence 
of a catastrophic disease certificate for malignancy in National Health 
Insurance (NHI)-Taiwan. 
 
5.1.2. Subjects receive at least one systemic antineoplastic treatment within 12 
weeks since trial enrollment, which includes chemotherapy, immunotherapy, 
hormonal, targeted and cellular therapy of whichever initial therapeutic intent 
(curative, palliative or salvage). 
 
5.1.3. Subjects fulfill either cancer cachexia or pre-cachexia. 
5.1.3.1. Cancer cachexia:  
A maximal weight loss of at least 5% from the baseline within 6 months in those 
whose BMI equivalent to or over 20 kg/m2 or at least 2% in those whose BMI 
less than 20 kg/m2.  
5.1.3.2. Pre-cachexia:  
A maximal weight loss of 1% to 5% from the baseline within 6 months in 
patients whose BMI equivalent to or over 20 kg/m2 or 1% to 2% in those whose 
BMI less than 20 kg/m2 plus any of the following: an elevated serum C-reactive 
protein above upper normal limits (ULN), impaired fasting glucose or known 
diabetes mellitus, use of high-dose corticosteroid (over 10 mg prednisone 
equivalent daily), hypogonadism (disease-related or iatrogenic) or insufficient 
calorie intake of less than 20 kcal/kg/day 
 
5.1.4. Subjects are in a clinical status with an expected life span exceeding 6 
months and Eastern Cooperative Oncology Group (ECOG) 0 to 1 or Karnofsky 
Performance Scale (KPS) 80 to 100 at trial enrollment. 
 
5.1.5. Subjects are physically and mentally capable and willing for conducting 
the planned physical training and agreed to comply the educational instructions 
and wearable devices during trial intervention. 
 
5.1.6. Subjects are functionally and cognitively capable to be informed of the 
trial contents and objectives (including obtaining peripheral blood sampling for 
trial investigation), and agree to sign the written consent for enrollment. 

 
8 
 
 
5.2 Exclusion criteria 
5.2.1. Subjects have tumor in situ or curatively treated malignant disease which 
requires no further antineoplastic treatments. 
 
5.2.2. Subjects are anticipated to receive any surgery, radiotherapy or 
intervention that prevents or hinders a planned physical training within 28 
weeks since trial enrollment. 
 
5.2.3. Subjects experience a progressive BWL which fulfills the criteria for 
cancer cachexia or pre-cachexia but complicates with the following causes: 
5.2.3.1. Severe oral or dental disorders that prevent reasonable intake of food 
per oral. 
5.2.3.2. Known functional or mechanical gastrointestinal disorders that 
prevent reasonable nutritional absorptions. 
5.2.3.3. Intentional body weight reduction by any measures. 
5.2.3.4. Known hormonal disorders that cause unintentional or pathogenic 
BWL. 
 
5.2.4. Subjects have cachexia caused by etiologies not limited to cancer as the 
following: 
5.2.4.1. Pulmonary cachexia which caused by chronic respiratory failure or 
chronic obstructive pulmonary disease. 
5.2.4.2. Cardiac cachexia which caused by chronic and persistent congestive 
heart failure. 
5.2.4.3. Cachexia related to acquired immunodeficiency syndrome. 
 
5.2.5. Subject’s malignant disease is considered unstable and thereby unfit for 
a planned physical training as the following: 
5.2.5.1. Uncontrolled or untreated symptomatic brain metastasis. 
5.2.5.2. Unstable or deteriorating organ dysfunction. 
5.2.5.3. Unstable or symptomatic bone metastasis. 
5.2.5.4. Cancer or treatment related physical disability. 
 
5.2.6. Subjects have an underlying medical illness causing severely impaired 
organ functions as the following: 
5.2.6.1. Any liver disease or cirrhosis above Child-Turcott-Pugh score B 
5.2.6.2. Any renal disease or insufficiency requiring regular dialysis or eGFR 

 
9 
 
≤30 mL/min/1.73 m2 as calculated by Modification of Diet in Renal Disease 
(MDRD) formula. 
5.2.6.3. Any heart failure with New York Heart Association functional class 
III-IV. 
5.2.6.4. Any pulmonary disease requiring daily oxygen support. 
5.2.6.5. Any bone, joint or soft tissue illness with range of motion limitations 
which prevents physical training of the limbs. 
 
5.2.7. Subjects have an active infection requiring hospitalized treatment or 
intravenous anti-pathogen therapies. 
 
5.2.8. Subjects who receive other experimental treatments or interventions for 
cancer cachexia. 
 
5.2.9. Subjects are planning to conceive or already in pregnancy. 
 
5.2.10. Subjects are currently participating in any other observational studies 
concerning cancer cachexia. 
 
 
6. STUDY DESIGN AND INTERVENTION PLANS 
The proposed study is an open-label, single-arm and single-center phase II 
investigator-initiated trial consisting of two parts. The first part is a feasibility 
testing and safety run-in cohort and followed by a hypothesis testing cohort as 
the second part. The primary objective is to investigate the feasibility and 
efficacy of a supervised intensity-modulated physical training program for 
elderly cancer patients with risk of cachexia. The primary endpoint is 
MiniCASCO reduction at week 12 and 24. The secondary endpoints are geriatric 
assessment, physical activity and sarcopenia. Exploratory objectives include 
HRQoL, cancer-related survival, recurrence/progression, cancer treatment or 
study intervention-related adverse events, nutritional scales and gait analysis. 
Enrolled subjects will receive physical training program per protocol until its 
completion, intolerability, death at any causes, subject’s refusal, investigator’s 
discretion or trial termination according to the principal investigator. A pre-
planned study schedule is due at week 24 with the following time points, week 
-4 to -2 (pre-screening), week -2 to 0 (screening and preparation or baseline), 
week 0 (intervention initiation), week 6 (intervention midway), week 12 
(completion) and week 24 (post-intervention follow-up). 

 
10 
 
 
 
Figure 1. Trial schema 
 
6.1 Overall protocol 
6.1.1. Aerobic exercise 
Intensity-modulated ergometer training will be provided in the SeniorGym, 
MDIC, National Cheng Kung University Hospital. Each session lasts 8 to 25 
minutes with a gradual increment of both resistance and duration along the 
training process. Two to three sessions per week will be arranged with a 
minimal interval of 24 hours between two consecutive sessions. Training 
targets are determined at a moderate intensity of aerobic exercise or reaching 
80% of mpHR. A total of 12-week training is provided to each subject when 
tolerated (week 0 to 12). 
 
6.1.2. Resistance exercise 
Trainer-assisted supervised manual physical training will be provided to the 
subjects in the SeniorGym, MDIC, National Cheng Kung University Hospital. 
The training module is composed of utilizing Therabands® to conduct limb or 
trunk stretching under reasonable resistance. Each session lasts 20 minutes 
with a gradual increment on resistance along the training process. Two sessions 
per week will be arranged with a minimal interval of 24 hours between two 
consecutive sessions. Training targets are determined at a moderate intensity 
of resistance exercise or reaching 80% of mpHR. A total of 12-week training is 
provided to each subject when tolerated (week 0 to 12). 
 
6.1.3. Nutrition assessment and intervention 
Nutrition assessment and intervention will be conducted by dieticians in 
specialized nutrition outpatient clinics. A professional diet consultation and 
nutritional recommendations will be provided upon willingness of the subject. 

 
11 
 
Dietary prescriptions will be determined and adjusted to a target daily calorie 
intake of 25 to 30 kcal/kg/day. Forty to fifty percent of the daily calorie is 
expected to derive from carbohydrate source. Protein ingestion is aimed at 1.2 
g/kg/day at least. Subjects will be visited at week 0, 12 and 24 for nutrition 
assessment, calorie calculation and dietary target adjustments. 
 
6.2 Screening and preparation 
6.2.1 Screening and pre-intervention assessment 
During the pre-screening period (week -4 to -2), study nurse will confirm the 
eligibility for enrollment, record the baseline demographics and clinical 
characteristics of the subject and prepare him/her for pre-intervention 
preparation. In addition, a written informed consent of the subject will be 
obtained under reasonable request to initiate the trial assessment and 
intervention. 
 
6.2.2 Preparation of exercise intervention 
A detailed introduction and education will be delivered at week -2 to week 0 
and the exercise intervention will be initiated at week 0. In addition, study 
nurses will complete pre-intervention assessment at week -2 to week 0 
(preparation). During week 0 (baseline), 6 (midway), 12 (completion) and 24 
(follow-up), all subjects will be reviewed and evaluated of the eligibility for 
continuation of exercise training or mid-, and post-intervention assessments. 
Subjects will be followed at a specialized outpatient clinic at week 0, 6, 12 and 
24, respectively. 
 
6.3 Modifications of intervention 
6.3.1 Exercise requirement:  
Subjects are required to be in generally well-being condition on each of the 
training session and assessment. Subjects will be asked for self-reported health 
or physical status on whether he or she feels suitable or comfortable to engage 
in each of the training session independently. In addition, subjects with any of 
the following subnormal vital biophysical readings, including HR (>180 or <60 
bpm), SBP (>160 or <90 mmHg) or pulse oximetry (SpO2<88% with ambient 
air) before each training session will be subjected to postpone or cancel the 
intervention under investigator’s discretion. 
 
6.3.2 Postponing exercise: 
If subjects fail to meet the aforementioned requirements to initiate or continue 

 
12 
 
a training session or assessment, a postponement is required. Each delay is set 
at a minimum of 2 consecutive days to a maximum of 28 consecutive days. 
Given the presence of delays in the intervention period, the pre-scheduled 
intervention midway (week 6), completion (week 12) and follow-up (week 24) 
time points are thereby postponed accordingly. 
 
6.3.3 Specific considerations: 
If the investigator or study nurse observes any signs or symptoms suggestive of 
physical or bodily injury or trauma related to the exercise training, given a 
permission from the subject, a delay is required until all harmful conditions are 
alleviated to baseline. The principle of delay will follow the guidance as 
described in 6.3.2. 
 
6.4 Off-study criteria 
Subjects who meet any one of the following conditions will be withdrawn from 
the study, 
▪ Clinical evidence of progression or recurrence of the malignant disease which 
prevents or hinders further physical training. 
▪ Delayed recovery of intervention-related injuries or comorbidities, which 
prohibits the protocol intervention beyond 28 consecutive days since the 
inciting physical exercise. 
▪ Unacceptable or unanticipated toxicity or adverse events 
▪ Subject’s death. 
▪ Subject’s refusal. 
▪ Investigator’s discretion to stop the protocol intervention. 
▪ Available and potentially better alternative treatments at the discretion of the 
investigator. 
▪ Confirmed futility or potential harms of the study intervention to the subjects, 
as determined by the chief principal investigator. 
 
 
7. STUDY SCHEDULE 
 
7.1 Assessment timeline 
The following assessments, including primary endpoint (MiniCASCO), geriatric 
assessment, physical activity, sarcopenia, HRQoL, nutrition assessment and 
gait analysis, are performed at the pre-scheduled timeline, respectively. In 
addition, cancer-related events, recurrence/progression of cancer, cancer 

 
13 
 
treatment or study intervention-related adverse events are recorded at 
whenever time points if present. We will implement a wearable device to record 
the motility of subjects during the intervention. The details and timetable for 
assessments of the trial are shown in 7.5 (Figure 2). 
 
7.1.1 Primary endpoint: MiniCASCO 
The endpoint is assessed and recorded at baseline (week -2 to 0), completion 
(week 12) and post-intervention follow-up (week 24). The evaluation tools and 
gradings are followed by MiniCASCO as reported by Argilés et al.13 Please refer 
to the descriptions in 8.1. 
 
7.1.2 Geriatric assessment: Integrated Care for Older People (ICOPE) 
The endpoint is assessed and recorded at baseline (week -2 to 0), completion 
(week 12) and post-intervention follow-up (week 24). Please refer to the 
descriptions in 8.2.1. 
 
7.1.3 Physical activity: hand grip strength, gait speed, body mass index (BMI), 
sit to stand (STS), back stretch, sit reach, single leg stand (SLS), up and go (UG), 
2-minute step (2MS), 6-minute walk test (6MWT) and timed up-and-go (TUG) 
The endpoint is assessed and recorded at baseline (week -2 to 0), midway (week 
6), completion (week 12) and post-intervention follow-up (week 24). Please 
refer to the descriptions in 8.2.2. 
 
7.1.4 Sarcopenia: sarcopenia-calf circumference (SARC-Calf) 
The endpoint is assessed and recorded at baseline (week -2 to 0), completion 
(week 12) and post-intervention follow-up (week 24). Please refer to the 
descriptions in 8.2.3. 
 
7.1.5 HRQoL: European Organisation for Research and Treatment of Cancer-
Quality of Life Cancer C30 (EORTC-QLQ C30; 10 questions)29 
The endpoint is assessed and recorded at baseline (week -2 to 0), completion 
(week 12) and post-intervention follow-up (week 24). Only 10 questions are 
included and appended in the MiniCASCO. Please refer to the descriptions in 
8.1.5. 
 
7.1.6 Nutrition: Mini Nutritional Assessment Short-Form (MNA-SF) 
The endpoint is assessed and recorded at baseline (week -2 to 0), completion 
(week 12) and post-intervention follow-up (week 24). Please refer to the 

 
14 
 
descriptions in 8.2.4. 
 
7.1.7 Gait analysis: Zebris gait 
The endpoint is assessed and recorded at baseline (week -2 to 0), completion 
(week 12) and post-intervention follow-up (week 24). Please refer to the 
descriptions in 8.2.5. 
 
7.2 Peripheral blood sampling 
Peripheral blood sampling by venous puncture will be performed at baseline 
(week -2 to 0), completion (week 12) and post-intervention follow-up (week 24). 
 
7.4 Wearable device 
Wearable non-invasive watches are applied to the subjects. Subjects are 
required to wear the watch over one of the limbs for 14 randomly selected 
consecutive days during baseline (week -2 to 0), midway (week 6) and 
completion (week 12). The watch will detect acceleration and sunlight exposure 
of the subject, in which that a post hoc algorithmic analysis would be applied to 
transform the digital data into daily activity. The information will be saved to a 
central hub periodically via portable memory devices. Analysis and calculation 
of the stored digital information will be de-identified and then reviewed by a 
blinded independent investigator. 
 
7.5 Timetable for assessments 
 
 

 
15 
 
 
Figure 2. Timetable for assessments in the trial 
a. Only 10 questions are included and as a part of MiniCASCO. 
b. According to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. 
 
 
8. EVALUATION OF INTERVENTION EFFICACY 
 
8.1 MiniCASCO 
8.1.1 Specification of assessment metrics: 
Assessment metrics according to MiniCASCO are implemented to each subject 
at baseline (week -2 to 0), intervention completion (week 12), and post-
intervention follow-up (week 24). Five dimensions of MiniCASCO are assessed 
independently, summed up as a total score ranging from 0 to 100 points and 
graded as minimal (0 to 14), mild (15 to 28), moderate (29 to 46) or severe 
cachexia (47 to 100). 
 
8.1.2 Weight (40%) 
In the dimension “Weight”, BWL and lean body mass (LBM) loss are accounted 
as two categories. BWL of 1 to 5%, 5 to 10%, 10 to 15%, 15 to 20% or >20% are 
given 6, 12, 18, 24 or 32 points, respectively. LBM loss >10% is given 8 points if 
presents. The dimension “Weight” constitutes a total of 40% in the MiniCASCO. 
 
8.1.2 Blood parameters (20%) 
In the dimension “Blood parameters”, metabolic, inflammation and 
immunosuppression associated parameters are accounted as three categories. 
In the metabolic category, serum albumin <3.2 mg/dL is given 4 points and 

 
16 
 
anemia with hemoglobin <12.0 g/dL is given another 4 points. Serum C-
reactive protein (inflammation) with 10.0 to 20.0 or >20.0 mg/L is given 4 or 
8 points. Absolute lymphocyte count (immunosuppression) with ≤500 
x104/mL is given 4 points. The dimension “Blood parameters” constitutes a 
total of 20% in the MiniCASCO. 
 
8.1.3 Physical performance (15%) 
In the dimension “Physical performance”, stair climbing and 500-meter walk 
are accounted. The questions “Did you have to put more effort on climbing 
stairs?” and “Have you felt tired after walking approximately half a 
kilometer?” are asked to the subject and replied by none, mild, moderate, or 
strong, as each is given 0, 2.5, 5.0 or 7.5 points, respectively. The dimension 
“Physical performance” constitutes a total of 15% in the MiniCASCO. 
 
8.1.4 Anorexia (15%) 
In the dimension “Anorexia”, appetite and food intake are accounted. Subjects 
are required to answer by “My appetite is (very good, good, average, poor or 
very poor)” and is given 0, 1.9, 3.8, 5.7, or 7.5 points in the appetite category. 
In the food intake category, subjects are asked to describe “When I eat (I hardly 
ever feel full, I feel full after eating most of the meal, I feel full after eating over 
half a meal, I feel full after eating about a third of a meal or I feel full after 
eating only a few mouthfuls” and is given 0, 1.9, 3.8, 5.7, or 7.5 points, 
respectively. The dimension “Anorexia” constitutes a total of 15% in the 
MiniCASCO. 
 
8.1.5 HRQoL (10%) 
In the dimension “HRQoL”, 10 standardized questions from EORTC-QLQ C30 
are asked to the subjects as the following: “Do you need to stay in bed or a chair 
during the day?”; “Were you limited in doing either your work or other daily 
activities?”; “Were you limited in pursuing your hobbies or other leisure time 
activities?”; “Have you had pain?”; “Did you need to rest?”; “Have you felt 
weak?”; “Did pain interfere with your daily activities?”; “Have you had 
difficulty in concentrating on things, like reading a newspaper or watching 
television?”; “Has your physical condition or medical treatment interfered 
with your family life?”; How would you rate your overall health during the 
past week?”. The answers are graded as none/not at all, a little/slightly, 
average/moderately, or a lot/considerably and each question is given 0, 0.25, 
0.75 or 1.0 point, respectively. The dimension “HRQoL” constitutes a total of 

 
17 
 
10% in the MiniCASCO. 
 
8.2 Other assessments 
8.2.1 ICOPE 
The World Health Organization (WHO) published Integrated Care for Older 
People Guidelines (ICOPE) to provide comprehensive assessment and person-
centered service to older populations to ensure healthy ageing 2017.30,31 ICOPE 
focuses on six domains of individual's physical and mental capacities, which 
includes (1) cognitive, (2) mobility, (3) nutrition, (4) visual, (5) hearing, (6) 
depressive symptoms. The Taiwan Health Promotion Administration 
subsequently added two domains, (7) medication and (8) life goals, to meet 
older people’s health and social care needs in Taiwan's socioeconomic context. 
People reporting declines in any domain of the ICOPE screening tool should 
continue for further evaluation using scales such as BHT, SPPB, MNA-SF, 
Simplified Visual Acuity Chart, and GDS-15 for a more in-depth assessment. 
With the ICOPE assessment, conditions in older people associated with 
functional decline can be identified. 
 
8.2.2 Physical activity 
The participants undergo physical examinations at baseline (week 0), midway 
(week 6), completion (week 12), and post-intervention follow-up (week 24). The 
Body Mass Index (BMI) is calculated as personal weight (in kilograms) divided 
by the square of height (in meters). 
 
8.2.2.1. 30-second sit-to-stand (STS) test:  
Participants are instructed to rise as fast as possible from a seat in 30 seconds 
with arms folded across the chest. The number of full stands in 30 seconds is 
recorded. 
8.2.2.2. Back stretch:  
Participants are asked to reach over the shoulder with one hand and extend the 
other one up the middle of the back. The distance (cm) between the extended 
middle fingers between both hands is then recorded. 
8.2.2.3. Sit reach:  
Participants sit on the edge of a chair, stretch out one leg, hands overlapped, 
and reach towards the toes. The distance between fingers and feet is recorded. 
8.2.2.4. Single leg stand (SLS):  
Assessed with a test that involves standing on one leg with eyes open. The 
subjects are asked to stand on one foot and maintain balance. The total time is 

 
18 
 
recorded, with more than 30 seconds counted as 30 seconds. 
8.2.2.5. Up and go (UG):  
Participants are instructed to get up from a seat, walk 8 feet, turn, and return 
to the seated position. The total time is recorded. 
8.2.2.6. 2-minute step (2MS):  
Participants are instructed to raise each knee to a point midway between the 
patella and iliac crest in 2 minutes. The score is the number of repetitions 
required for the right knee to reach the target height. 
8.2.2.7. 6-minute walk test (6MWT):  
Participants are asked to walk for 6 minutes in a 30-meter-long quiet corridor. 
The total distance that the participants walk during the period is recorded. 
8.2.2.8. Timed up-and-go (TUG):  
Uses the time that a person takes to rise from a chair, walk 3 meters, turn 
around 180 degrees, walk back to the chair, and sit down while turning 180 
degrees. Participants can use a walking aid if needed. 
 
8.2.3 SARC-Calf 
SARC-CalF is a questionnaire that rapidly screens sarcopenia. In accordance 
with the 2019 Asian Working Group for Sarcopenia (AWGS) criteria, the SARC-
CalF scale contains six objects: (1) strength, (2) walking assistance, (3) rising 
from a chair, (4) climbing stairs, and (5) falls, and (6) is calf circumference (CC). 
CC thresholds are 34 and 33 cm for men and women, respectively. If the score 
is above the cut-off value, CC is scored as 0; if it is below the cut-off value, the 
score is 10. The maximal score of the SARC-CalF is 20 points. A total score of 
≥11 points indicate the risk of sarcopenia. 
 
8.2.4 MNA-SF 
The MNA-SF is a validated nutrition screening and assessment tool that can 
identify geriatric patients aged 65 or above who are malnourished or at risk of 
malnutrition. It is a screening tool consisting of six questions on food intake, 
weight loss, mobility, psychological stress, or acute disease, the presence of 
dementia or depression, and body mass index (BMI). The maximum score for 
this part is equal to 14. A score equal to or higher than 12 indicates that the 
subject under study has an acceptable nutritional status thus excluding 
malnutrition and/or malnutrition risk, meanwhile, a score ≤ 11 implicates to 
proceed with the complete version of the MNA (MNA-LF).   
 
8.2.5 Zebris gait 

 
19 
 
The Zebris gait analysis system is used to obtain numerical data for kinetic and 
kinematic gait parameters (Zebris Medical GmbH, Isny im Allgau, Germany). 
The pressure platform has a sensing area of 149 x 54.2 cm and the sensor unit 
has 11,264 pressure/force sensors. The foot is mapped at high resolution to 
facilitate the detection of even the subtlest changes in force distribution, 
including center of pressure (COP) trajectories during static stance and gait. 
The gait pattern is collected and analyzed to investigate the effect of 
intervention. 
 
9. STATISTICAL CONSIDERATION 
In the proposed study, a two-staged design is utilized as an optimal 
arrangement of the subjects. We assume a statistical power of 80% (β=0.2) and 
the probability of type I error by two-tailed α at 0.1. According to our 
preliminary results, we found the MiniCASCO (n=11, mean ±SD=22 ±5) of the 
identical study target population. We hypothesize a 10% of reduction of 
MiniCASCO in elderly cancer patients with risk of cachexia post intervention. 
A minimum of 49 subjects are required under the optimal assumption. We 
presume the part I as a safety run-in period enrolling 10 subjects to assess the 
feasibility and safety of the protocol. After the confirmation by the principal 
investigator, the remaining 39 subjects will be enrolled as part II. In summary, 
a total of 49 subjects will be enrolled to meet the prespecified statistical 
threshold. 
 
 
10. REPORTING OF SEVERE ADVERSE EVENTS TO 
INSTITUTIONAL REVIEW BOARD (IRB) OF ETHICS 
 
10.1 Reporting events to IRB 
All investigators must receive adequate professional training according to the 
Good Clinical Practice (GCP) guideline, be approved by the IRB, abide to the 
related obligations and be accredited for clinical trial investigations. Serious 
adverse events/Suspected unexpected serious adverse reactions/Unanticipated 
problems (SAE/SUSAR/UP) must be reported in written form to the PI 
immediately. The PI will then report to IRB within 72 hours. The events are 
defined as any of those described in sections 10.1.1. to 10.1.6. below. However, 
serious events occurring after the subject is withdrawn from the study do to 
warrant mandatory reporting under the investigator’s discretion. Events which 
are anticipated morbidities associated with malignancy and chemotherapy are 

 
20 
 
waived from the reporting. 
 
10.1.1 Causes death 
Study-specific clinical outcomes of death because of cancer progression are 
excluded from the reporting unless the investigator deems the death related to 
the study intervention. 
 
10.1.2 Are life-threatening. 
 
10.1.3 Causes severe or permanent disability. 
 
10.1.4 Causes prolonged inpatient hospitalization. 
 
10.1.5 Causes congenital anomaly. 
 
10.1.6 Is significant for any other reasons. 
 
11. OTHERS 
 
11.1 All patients must have a signed Informed Consent form and an on-study 
(confirmation of eligibility) form filled out and signed by a responsible 
investigator before entry. 
 
11.2 The responsible study investigators and research nurses must approach 
each patient prior to study drug administration. All required pre-intervention 
and interim information should be available and the investigators must decide 
if a re-evaluation is needed and the grade of intervention-related toxicity or 
adverse events if present. 
 
11.3 Data must be recorded before a course of intervention can be given. A brief 
explanation for required but missing data should be recorded as a comment. 
 
 
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