Pilot Study of Oral Cryotherapy vs. Oral Cryotherapy Plus Acupuncture and Acupressure to Decrease Chemotherapy-Induced Peripheral Neuropathy From Oxaliplatin-Based Chemotherapy for GI Cancers
Phase: PHASE2
Conditions: Appendix Carcinoma, Colon Carcinoma, Esophageal Carcinoma, Gastric Carcinoma, Liver and Intrahepatic Bile Duct Carcinoma, Malignant Digestive System Neoplasm, Pancreatic Carcinoma, Rectal Carcinoma, Small Intestinal Carcinoma, Anal Carcinoma, Digestive System Carcinoma, Digestive System Neuroendocrine Tumor, Pancreatic Neuroendocrine Tumor
Sponsor: University of Washington

 
 
Official Title 
Pilot study of oral cryotherapy vs. oral cryotherapy plus 
acupuncture and acupressure to decrease 
chemotherapy-induced peripheral neuropathy from 
oxaliplatin-based chemotherapy for GI cancers 
NCT Number 
NCT04505553 
Document Type 
Protocol and Statistical Analysis Plan 
Document Date 
6/27/2023 
 
 

RG1121095
Page 1 of 44
Version 9, 19May2023 
FRED HUTCHINSON CANCER RESEARCH CENTER 
UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE 
SEATTLE CHILDREN’S
Current version: 9 
Previous version: 09/28/2022
Title of Protocol:
Pilot study of oral cryotherapy vs. oral cryotherapy plus acupuncture and acupressure to decrease
chemotherapy-induced peripheral neuropathy from oxaliplatin-based chemotherapy for GI cancers
Investigators List:
Investigator
Professional Title
Phone Number
Stacey Cohen, MD
Associate Professor of Medicine, UW 
Associate Professor, Fred Hutch
(206) 606-6658
Heather Greenlee, ND PhD, MPH
Associate Professor, Fred Hutch
Associate Professor of Medical Oncology, UW
Medical Director, Integrative Medicine, SCCA
(206) 667-4502
Jonathan Siman, DACM, LAc, MS
Staff Acupuncture Supervisor
(206) 606-1928
Susan Veleber, DACM, LAc, MS
Staff Acupuncturist
(206) 606-1905
Kerry McMillen, MS, RD CD
Medical Nutrition Therapy Manager
(206) 606-2136
Biostatistician:
Katherine A. Guthrie, PhD
Professor, Public Health Sciences Division, Fred Hutch
(206) 667-5595
Funding source: Safeway Early Career/Cancer Center Support Grant Pilot Award
Emergency (24-hour) phone number: (206) 598-6190
Document Released Date
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 2 of 44
Version 9, 19May2023 
1.0 ABBREVIATIONS
5-FU
5-fluorouracil
BPI
Brief pain inventory
CRF
Case report form
CIPN
Chemotherapy-induced peripheral neuropathy
CRS
Clinical Research Support
CTCAE
Common Terminology Criteria for Adverse Events
DSMP
Data and Safety Monitoring Plan
DSMC
Data and Safety Monitoring Committee
EOT
End-of-treatment
FOLFIRINOX
FOLFOXIRI
5-FU, oxaliplatin, irinotecan
FOLFOX
5-FU, oxaliplatin
IRB
Institutional Review Board
GI
Gastrointestinal
SNRI
Selective serotonin-norepinephrine reuptake inhibitor
SRC
Scientific Review Committee
SSRI
Selective serotonin reuptake inhibitor
TCM
Traditional Chinese Medicine
UW
University of Washington
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 3 of 44
Version 9, 19May2023 
2.0 PROTOCOL SYNOPSIS
Protocol Title
Pilot study of oral cryotherapy vs. oral cryotherapy plus acupuncture and 
acupressure to decrease chemotherapy-induced peripheral neuropathy from
oxaliplatin-based chemotherapy for GI cancers
Protocol Number
Pending
Protocol Funding
Safeway Early Career/Cancer Center Support Grant Pilot Award
Trial Phase
Phase II
Trial Type
Randomized Control Feasibility Trial
Clinical Indication
GI cancer for which a new oxaliplatin-based regimen is recommended
Study Objectives
Primary:
To evaluate the severity of CIPN in GI cancer patients receiving oxaliplatin-based 
chemotherapy following 3 months of acupuncture/acupressure treatment plus oral 
cryotherapy compared to oral cryotherapy alone.
Secondary 1:
To estimate the incidence of grade 2 or higher CIPN in GI cancer patients receiving 
oxaliplatin-based chemotherapy following 3 months of acupuncture/acupressure 
treatment plus oral cryotherapy compared to oral cryotherapy alone.
Secondary 2:
To evaluate the severity of CIPN in GI cancer patients receiving oxaliplatin-based 
chemotherapy following 3 months of acupuncture/acupressure treatment plus oral 
cryotherapy compared to oral cryotherapy alone using objective measurement tools.
Secondary 3:
To assess the feasibility of delivering acupuncture during biweekly chemotherapy 
infusion and the feasibility of patient self-administered acupressure between 
infusions.
Secondary 4:
To evaluate the effect of oral cryotherapy with acupuncture/acupressure vs. oral 
cryotherapy alone in reducing pain, fatigue, nausea, oral dysesthesia, and anxiety in
GI cancer patients receiving oxaliplatin-based chemotherapy.
Study Design
Randomized Controlled Feasibility Trial
Population
56 patients with a GI cancer malignancy with planned ≥3 months of a 5-FU- and 
oxaliplatin-based chemotherapy regimen. Eligibility criteria includes: 1) GI cancer 
(primary esophagus, gastric, pancreas, biliary, small bowel, appendix, colon, or 
rectal) scheduled to receive a new start of 5-FU, oxaliplatin, ± irinotecan [FOLFOX, 
FOLFIRINOX, FOLFOXIRI regimens] with plan for ≥3 months of therapy with the 
regimen, 2) age ≥18 years, 3) absolute neutrophil count >500 and platelet count
>20,000, 4) not currently pregnant, 5) ability to understand and the willingness to 
sign a written informed consent document, 6) no baseline neuropathy from any 
cause, 7) no prior neurotoxic chemotherapy of any kind in the prior 3 years, 8) no 
planned initial dose of oxaliplatin <100% of the standard regimen-specified dose, 9) 
no receipt of acupuncture treatment in the prior 3 months, 10) no use of 
concomitant duloxetine for minimization of neuropathy, 11) no psychiatric
illness/social situations that would limit compliance with study requirements.
Primary Endpoint
Chemotherapy-induced peripheral neuropathy as measured by the EORTC-CIPN 20.
Secondary Endpoints
1. Incidence of grade 2 or higher CIPN as measured by CTCAE version 5.
2. Severity of chemotherapy-induced peripheral neuropathy as measured by a 
Neuropen and tuning fork.
3. Proportion of patients assigned to the intervention arm who complete 60% of 
acupuncture treatments.
4. Incidence of pain, fatigue, nausea, oral dysesthesia, and anxiety as measured by 
the NCI PRO-CTCAE, Brief Pain Inventory (BPI), and CTCAE version 5.
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 4 of 44
Version 9, 19May2023 
Type of control
Usual care + waitlist arm – receives no acupuncture during the 3-month 
intervention period
Investigation Drug
N/A
Dose
Acupuncture: 12 treatments with 30-minute needle retention
Route of administration
Acupuncture: filiform needle insertion
Regimen
12 sessions of acupuncture. Acupressure training and self-treatment.
Trial Blinding
None
Treatment Groups
Arm A: Acupuncture + Acupressure Intervention with standard-of-care cryotherapy: 
acupuncture during chemotherapy infusion (day 1) and 5-FU pump disconnect (day
3) of each biweekly chemotherapy infusion x6 cycles (i.e. 12 acupuncture 
treatments over 12 weeks) + self-acupressure
Arm B: Waitlist Control Arm with standard-of-care cryotherapy: 6 acupuncture
sessions after the completion of the trial
Treatment Schedule
Days 1 and 3 of each chemotherapy treatment cycle
Efficacy Assessments
Baseline 
6 weeks
12 weeks
Number of trial subjects
56
Estimated duration of trial
24 months
Duration of Participation
3 months
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 5 of 44
Version 9, 19May2023 
3.0 Table of Contents
1.0
ABBREVIATIONS ................................................................................................................................................................2
2.0
PROTOCOL SYNOPSIS........................................................................................................................................................3
3.0
Table of Contents..............................................................................................................................................................5
4.0
GENERAL INFORMATION ..................................................................................................................................................8
1.1
Protocol Title........................................................................................................................................................8
5.0
INTRODUCTION TO THE PROTOCOL .................................................................................................................................8
5.1
Introduction.........................................................................................................................................................8
5.2
Clinical Data with Cryotherapy.............................................................................................................................8
5.3
Clinical Data with Acupuncture and Acupressure................................................................................................8
5.4
Risks/Benefits.......................................................................................................................................................8
6.0
OVERVIEW OF CLINICAL TRIAL..........................................................................................................................................9
6.1
Study Objectives ..................................................................................................................................................9
6.2
Study Population..................................................................................................................................................9
6.3
Study Design ........................................................................................................................................................9
6.4
Estimated Accrual ................................................................................................................................................9
6.5
Name of Sponsor/Funding Source .......................................................................................................................9
7.0
SUBJECT ELIGIBILITY..........................................................................................................................................................9
7.1
Inclusion Criteria..................................................................................................................................................9
7.2
Exclusion Criteria ...............................................................................................................................................10
8.0
SUBJECT REGISTRATION..................................................................................................................................................10
9.0
TREATMENT PLAN...........................................................................................................................................................11
9.1
Treatment Plan Overview ..................................................................................................................................11
9.2
Acupuncture and Acupressure Intervention......................................................................................................11
9.3
Cryotherapy .......................................................................................................................................................12
9.4
Waitlist Control..................................................................................................................................................12
9.5
Concomitant Medication and Supportive Care Guidelines................................................................................12
9.6
Duration of Therapy...........................................................................................................................................12
9.7
Duration of Follow-Up .......................................................................................................................................12
9.8
Dosing Delays/Dose Modifications ....................................................................................................................12
9.9
End of Treatment (EOT) Visit Schedule and Procedures....................................................................................12
10.0
SUBJECT EVALUATION.....................................................................................................................................................13
10.1
On-Study Clinical Evaluations.............................................................................................................................13
10.2
Quality of Life Assessments ...............................................................................................................................13
10.3
Neuropathic Assessments..................................................................................................................................13
10.4
Acupuncture Expectancy Scale ..........................................................................................................................15
11.0
SUBJECT DISCONTINUATION OF ACTIVE TREATMENT....................................................................................................15
12.0
CONCOMITANT MEDICATIONS .......................................................................................................................................16
13.0
ADVERSE EVENTS ............................................................................................................................................................16
13.1
Adverse Event ....................................................................................................................................................16
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 6 of 44
Version 9, 19May2023 
13.2
Serious Adverse Event........................................................................................................................................16
13.3
Unexpected Adverse Event................................................................................................................................16
13.4
Monitoring and Recording Adverse Events........................................................................................................17
13.5
Grading Adverse Event Severity.........................................................................................................................17
13.6
Attribution of an Adverse Event ........................................................................................................................17
13.7
Adverse Event Recording Period........................................................................................................................17
13.8
Adverse Event Reporting Requirements............................................................................................................17
14.0
DATA AND SAFETY MONITORING PLAN..........................................................................................................................17
15.0
DATA MANAGEMENT/CONFIDENTIALITY .......................................................................................................................18
16.0
STATISTICAL CONSIDERATIONS.......................................................................................................................................18
16.1
Study Design ......................................................................................................................................................18
16.2
Primary/Secondary Endpoints and Analytical Methods ....................................................................................18
16.3
Sample Size and Power ......................................................................................................................................18
16.4
Randomization...................................................................................................................................................18
16.5
Statistical Analysis..............................................................................................................................................18
16.6
Ethnic and Gender Distribution Chart................................................................................................................19
17.0
INVESTIGATOR OBLIGATIONS .........................................................................................................................................19
18.0
ADMINISTRATIVE AND REGULATORY CONSIDERATIONS................................................................................................19
18.1
Pre-Study Documentation .................................................................................................................................19
18.2
Study Site Training .............................................................................................................................................19
18.3
Documentation..................................................................................................................................................20
18.4
Access to Source Data........................................................................................................................................20
18.5
Data Collection...................................................................................................................................................20
18.6
Protocol Interpretation and Compliance ...........................................................................................................20
18.7
Disclosure of Data/Publication...........................................................................................................................20
18.8
Ethical Considerations........................................................................................................................................20
18.9
Informed Consent ..............................................................................................................................................20
18.10
Institutional Review Board/Ethics Committee...................................................................................................21
18.11
Subject Privacy...................................................................................................................................................21
19.0
REFERENCES....................................................................................................................................................................22
20.0
APPENDICES ....................................................................................................................................................................23
20.1
APPENDIX A: ECOG Performance Status Scale...................................................................................................24
20.2
APPENDIX B: Study Calendar..............................................................................................................................25
20.3
APPENDIX C: Location of Acupuncture and Acupressure Points........................................................................26
20.4
APPENDIX D: EORTC QLQ CIPN-20 .....................................................................................................................28
20.5
APPENDIX E: NCI PRO-CTCAE .............................................................................................................................30
20.6
APPENDIX F: Brief Pain Inventory ......................................................................................................................32
20.7
APPENDIX G: Oral symptoms questionnaire......................................................................................................33
20.8
APPENDIX H: Neuropen Assessment Points.......................................................................................................34
20.9
APPENDIX I: Tuning Fork Assessment Points .....................................................................................................35
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 7 of 44
Version 9, 19May2023 
20.10
APPENDIX J: Acupressure Diary .........................................................................................................................37
20.11
APPENDIX K: Acupuncture Expectancy Scale.....................................................................................................39
20.12
APPENDIX L: Acupressure Ear Seed Care Instructions .......................................................................................40
20.13
APPENDIX M: Waitlist Acupuncture Voucher ....................................................................................................41
20.14
APPENDIX N: Research Acupuncture Appointments in the Wellness Clinic ......................................................42
20.15
APPENDIX O: Cryotherapy Phone Script ............................................................................................................43
20.16
APPENDIX P: Cryotherapy Questionnaire ..........................................................................................................44
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 8 of 44
Version 9, 19May2023 
1.1
Protocol Title
Pilot study of oral cryotherapy vs. oral cryotherapy plus acupuncture and acupressure to decrease chemotherapy-induced 
peripheral neuropathy from oxaliplatin-based chemotherapy for GI cancers
5.1 Introduction
Chemotherapy-induced peripheral neuropathy (CIPN) negatively impacts treatment delivery, both acutely (by requiring dose 
reductions, delays, or requiring early cessation of treatment) and chronically (by impacting quality of life for survivors). CIPN 
is a common side effect of oxaliplatin, which is a component of the majority of standard adjuvant and/or first-line metastatic 
therapies for gastroesophageal, pancreas, and colorectal cancer patients. In the MOSAIC trial of adjuvant 5-fluorouracil (5- 
FU) and oxaliplatin [FOLFOX], >90% of colon cancer patients reported CIPN during treatment, with 15% reporting symptoms 
four years later.1 Similarly, in pancreas cancer patients receiving six months of 5-FU, irinotecan, and oxaliplatin [FOLFIRINOX] 
in the adjuvant setting, 61% had any-grade CIPN and 9-10% had grade 3+ CIPN in the landmark adjuvant and metastatic 
trials.2, 3 The high prevalence of acute and persistent CIPN in multiple gastrointestinal (GI) cancer patient populations 
highlights the need to more effectively mitigate acute and chronic CIPN.
In additional to peripheral neuropathy symptoms, as a result of oxaliplatin administration, patients can experience 
oral dysesthesia, which can negatively impact oral intake. Patients are typically educated to avoid cold foods and fluids, which 
can significantly impact food choices and eating/drinking overall during the acute symptoms of neurotoxicity.4 This is 
especially problematic in GI cancers, where digestion and oral intake are often compromised by the cancer itself.
Complementary therapies have been tested in the prevention and treatment of CIPN, with few effective treatments 
identified.5 Calcium and/or magnesium infusions with oxaliplatin were standard-of-care for prevention of CIPN, but were 
unsupported by a large randomized trial.6 Newer efforts have included both cryotherapy and acupuncture.
5.2 Clinical Data with Cryotherapy
Oral ice chip cryotherapy has recently been introduced as a method to prevent oral thermal hyperalgesia, thought to be 
mediated by vasoconstriction.7 In this single institution study, 62 patients were randomized and 50 were evaluable (having 
received at least 2 cycles) for either oral ice chip cryotherapy, delivered for 120 minutes during oxaliplatin infusion versus a 
control group, who was asked to avoid ingesting anything cooler than room temperature for the duration of the infusion. 
Using a scoring system, the ice chip cryotherapy intervention group had less oral and peripheral neuropathy symptoms prior 
to cycle 2 as compared to the control group. This was also demonstrated longitudinally. The benefit from oral ice chip 
cryotherapy was dose-dependent, meaning that longer ice duration was associated with less CIPN. Based on this data, ice 
chip cryotherapy (in the form of oral ice, hand/foot ice packs) was adopted into standard clinical practice.
5.3 Clinical Data with Acupuncture and Acupressure
Acupuncture has been explored as a safe nonpharmacological method of preventing and treating CIPN. The mechanisms of 
acupuncture are not fully understood. Acupuncture has been shown to work by adjusting neurophysiologic and 
neurohormonal activity.8, 9 Prior trials have had inconsistent results, likely due to differences in acupuncture protocols, use 
of electroacupuncture, timing of intervention, choice of comparator, and sample size, but the recent data suggests promise 
for using acupuncture for CIPN prevention.10-15
Acupressure has also demonstrated efficacy in decreasing fatigue, nausea, pain and improving quality of life in cancer 
patients.16-21 A 2019 Systematic Review and Meta-Analysis found a moderate level of evidence that acupuncture and/or 
acupressure compared to a sham control were significantly associated with lower intensity in cancer-related pain inpatients 
with cancer, which suggests a potential for a combination of acupuncture with acupressure to reduce the amount of cancer- 
related pain that may require opioid use as a treatment.21 Acupuncture and acupressure have potential to be scalable 
treatments for CIPN because they are both reproducible and standardized. Acupressure is an inexpensive and easy-to- 
perform self-care intervention.
5.4 Risks/Benefits
Oral cryotherapy and acupuncture have yet to be systemically tested together to assess this combination for maximal 
prevention of the onset and progression of CIPN. However, it is well recognized that CIPN can have acutely and chronically 
negatively impact quality of life. As there are few effective treatments outside of withdrawing the offending agent, prevention 
and minimization of neuropathic toxicities is highly necessary.
5.0
INTRODUCTION TO THE PROTOCOL
4.0
GENERAL INFORMATION
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 9 of 44
Version 9, 19May2023 
6.1 Study Objectives
6.1.1
Primary Objectives
To evaluate the severity of CIPN in GI cancer patients receiving oxaliplatin-based chemotherapy following 3 months of 
acupuncture/acupressure treatment plus oral cryotherapy compared to oral cryotherapy alone.
6.1.2
Secondary Objectives
1: To estimate the incidence of grade 2 or higher CIPN following 3 months of acupuncture/acupressure treatment plus oral 
cryotherapy compared to oral cryotherapy alone.
2: To evaluate the severity of CIPN in GI cancer patients receiving oxaliplatin-based chemotherapy following 3 months of 
acupuncture/acupressure treatment plus oral cryotherapy compared to oral cryotherapy alone using objective measurement 
tools.
3: To assess the feasibility of delivering acupuncture during biweekly chemotherapy infusion and the feasibility of patient 
self-administered acupressure between infusions.
4: To evaluate the effect of oral cryotherapy with acupuncture/acupressure vs. oral cryotherapy alone in reducing pain, 
fatigue, nausea, oral dysesthesia, and anxiety in GI cancer patients receiving oxaliplatin-based chemotherapy.
6.2 Study Population
Patients with a GI cancer malignancy with planned ≥3 months of a 5-FU- and oxaliplatin-based chemotherapy regimen.
6.3 Study Design
6.3.1
Primary Endpoint
Severity of CIPN as measured by the EORTC-CIPN 20.
6.3.2
Secondary Endpoints
Incidence of grade 2 or higher CIPN as measured by CTCAE version 5. 
Severity of CIPN as measured by a Neuropen and tuning fork.
Proportion of patients assigned to the intervention arm who complete 60% of acupuncture treatments.
Incidence of pain, fatigue, nausea, oral dysesthesia, and anxiety as measured by the NCI PRO-CTCAE, BPI, and CTCAE version 
5.
6.4 Estimated Accrual
Fifty-six patients will be enrolled, 28 randomized to each arm.
6.5 Name of Sponsor/Funding Source
This study is funded by a Safeway / Cancer Center Support Grant Pilot Award.
7.1 Inclusion Criteria
7.1.1
GI cancer (primary esophagus, gastric, pancreas, biliary, liver, small bowel, appendix, 
colon, rectal, anal, or gastrointestinal/pancreatic neuroendocrine tumor) scheduled to 
receive a new start of 5-FU, oxaliplatin, ± irinotecan [FOLFOX, FOLFIRINOX, FOLFOXIRI 
regimens] with plan for ≥3 months of therapy with the regimen
Chemotherapy can be given for neoadjuvant, adjuvant, or palliative intent.
6.0
OVERVIEW OF CLINICAL TRIAL
7.0
SUBJECT ELIGIBILITY
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 10 of 44
Version 9, 19May2023 
1 dose (cycle) of the intended regimen is permitted prior to study enrollment.
There is no limitation on the addition of a biologic agent to one of the above chemotherapy regimens, 
including, but not limited to: bevacizumab, cetuximab, panitumumab, trastuzumab, or the biosimilars 
of these agents.
7.1.2
Age ≥18 years
7.1.3
Absolute neutrophil count >0.5 thousand/microL and platelet count >20 thousand/microL
7.1.4
Not currently pregnant
7.1.5
Ability to understand and the willingness to sign a written informed consent document.
7.2 Exclusion Criteria
7.2.1
Baseline peripheral neuropathy from any cause
7.2.2
Planned oxaliplatin with capecitabine
7.2.3
Planned initial dose of oxaliplatin <100% of the standard regimen-specified dose
For most regimens, this would be 85mg/m2 IV dosed every 14 days.
7.2.4
Receipt of acupuncture treatment in the prior 3 months
7.2.5
Use of concomitant duloxetine for minimization of neuropathy.
7.2.6
Psychiatric illness/social situations that would limit compliance with study requirements.
Subjects will be registered by the Fred Hutch/UW Study Coordinator and their data entered into OnCore CTMS. A complete, 
signed, study consent and HIPAA consent are required for registration.
8.0
SUBJECT REGISTRATION
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 11 of 44
Version 9, 19May2023 
56 patients will be randomized 1:1 to the intervention arm (n=28) of standard oral cryotherapy with acupuncture or the 
control arm (n=28) of oral cryotherapy alone. All patients will receive standard-of-care supportive care medications 
(analgesics, antiemetics, etc.) at the discretion of their treating physician.
9.1 Treatment Plan Overview
9.2 Acupuncture and Acupressure Intervention
The intervention group will receive acupuncture during chemotherapy infusion (day 1) and 5-FU pump disconnect 
(day 3) of each biweekly chemotherapy infusion x6 cycles (i.e. 12 acupuncture treatments over 12 weeks). Acupuncture 
treatments will be specifically targeted to prevent, treat, or mitigate neuropathy symptoms, pain, fatigue, nausea and anxiety. 
Patients will receive 30-minute acupuncture treatments in the seated or supine position. Standard acupoint techniques for 
point location22 will be utilized and Clean Needle Technique23 will be followed using 32-40-gauge x 30-40mm Seirin 
acupuncture needles.
On day 1 the acupuncture points will be needled bilaterally at: ST36, SP6, LI10, GB40, P6, auricular shen men, and 
on the midline at Yin Tang (EX-HN3) and GV20. On day 3 the acupuncture points will be needled bilaterally at: LI4, LR3, ST36, 
SP6, LI10, GB40, P6, auricular shen men, and on the midline at Yin Tang (EX-HN3) and GV20. For patients unable to tolerate 
peripheral cryotherapy, the day 3 acupuncture protocol will be administered on day 1.
After the initial acupuncture treatment, the study acupuncturist will instruct the patient on how to locate and self- 
administer acupressure for key acupoints: bilateral LI4 (for pain, oral dysesthesia), bilateral P6 (nausea), and midline GV20 
(fatigue). These acupoints are based on previously published studies,12-15 Traditional Chinese Medicine (TCM) theory,22 and 
current understanding of innervation and neuromodulation of acupoints.13 Auricular shen men points (anxiety) will be 
stimulated with vaccaria seeds applied by the acupuncturists on day 3 and removed after 4 days (day 7 of the cycle). Patients 
will be taught to self-administer an 11-minute acupressure regimen daily by stimulating each acupoint in a circular motion 
for 2 minutes on each bilateral points of LI4 and P6, 2 minutes on midline GV20, and to gently press the ear seeds on shen 
men for 30 seconds three times per day. The acupuncturists will provide additional teaching during the acupressure training 
on Cycle 1 Day 1 instructing the patients to utilize auricular Shen Men point during cryotherapy to help mitigate possible 
unpleasant effects of cryotherapy including: headache, toothache, and/or cold aversion/pain.
9.0
TREATMENT PLAN
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 12 of 44
Version 9, 19May2023 
If a patient misses an acupuncture session, it will not be made up. If a patient misses both sessions from study cycle 
1 of chemotherapy, they will be removed from the study. Handouts describing acupuncture and acupressure will be provided 
to participants (Appendix L).
9.3 Cryotherapy
As per Seattle Cancer Care Alliance protocol, patients will hold ice chips in the mouth from up to 30 min prior through the 
end of the oxaliplatin infusion. The use and duration of ice chip exposure will be documented. Additionally, the use of ice 
packs on hands and/or feet (which is allowed, but not part of current standard-of-care cryotherapy) will also be documented. 
Duration of each will be recorded as 0, 1-30, 31-60, 61-90, 91-120, or >120 minutes. Patients will be given the Cryotherapy 
Questionnaire (Appendix O) on the day of infusion or contacted by study staff within 5 days of completion of their 
chemotherapy infusion and patient self-recall will be used to determine the method and duration of their cryotherapy 
(Appendices O and P). The Questionnaire may also be sent via email to be complete in the study portal.
9.4 Waitlist Control
To increase participant willingness to be randomized and to increase trial retention, participants randomized to the control 
arm will receive coupons for six acupuncture treatments at SCCA South Lake Union clinic to be used any time after completion 
of the individual’s duration (approximately 12 weeks) on the study (Appendices M and N). At the time of these visits, AEs and 
limited exam findings may be collection, which will be entered into the database as well. These visits will ideally be during or 
coordinated with standard-of-care visits. However, if patients have completed treatment, they may attend acupuncture-only 
visits.
9.5 Concomitant Medication and Supportive Care Guidelines
The use of duloxetine and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) are not permitted while on this 
study. Selective serotonin reuptake inhibitors (SSRIs) are permitted if prescribed for an indication other than the treatment 
of neuropathy (such as depression or anxiety).
Additional medications prescribed for the treatment of chemotherapy-induced peripheral neuropathy are not 
permitted. This includes gabapentin, alpha lipoic acid, B complex vitamin (or B1, B6, B12). These agents are permitted if 
prescribed for another indication.
Standard-of-care supportive care is recommended for the treatment of fatigue, pain, nausea, oral dysesthesia, and 
anxiety, and any other symptoms related to cancer or chemotherapy treatment.
9.6 Duration of Therapy
The intervention will be delivered over 3 months, concurrent with chemotherapy.
9.7 Duration of Follow-Up
Patients will not be followed after the intervention and end-of-treatment questionnaires are complete, with the exception of 
collection of data during waitlist control acupuncture visits if these are pursued.
9.8 Dosing Delays/Dose Modifications
Dose modifications, hold, and other alterations to planned chemotherapy will be at the discretion of the treating physician. 
Acupuncture treatments will be moved accordingly to co-occur with the chemotherapy treatments. If a patient discontinues 
use of oxaliplatin, he/she may continue to receive acupuncture either weekly or as protocolized (twice weekly every other 
week) until the completion of 3 months duration of acupuncture treatment.
9.9 End of Treatment (EOT) Visit Schedule and Procedures
The EOT visits for all subjects who discontinue from the study should ideally occur 14 days after day 1 of the prior cycle of 
chemotherapy (which would be 11 days from the last acupuncture treatment). The EOT visit is permitted in the range of 7- 
30 days after the last use of (Arm A) acupuncture treatment or (Arm B) cryotherapy use but must occur prior to beginning 
another treatment or receiving another dose of chemotherapy. Procedures to be performed during the EOT Visit include:

Physical Exam

Administration of the final QOL measures

Vital Signs

Performance Status

AE Assessment

Concomitant Medication
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 13 of 44
Version 9, 19May2023 
As per 6.7. patients who are on the waitlist control arm and choose to use their acupuncture coupons will have the official 
EOT visit for uniform data collection, but will also have limited data collected at the time of each acupuncture session to note 
any toxicities or major symptoms at the time of those visit.
10.1 On-Study Clinical Evaluations
Clinical evaluations take place according to the Study Calendar (Appendix B). The window between these visits should be as 
close to the scheduled time as possible, though delays in chemotherapy treatment as recommended by the treating 
physician are permitted and do not require cessation of protocol therapy.

Vitals
o
Include blood pressure, pulse, temperature

Physical Exam

Performance Status
o
As per the ECOG performance scale (see Appendix A)

Labs (day 1 of each cycle, or up to 3 days prior):
o
Hematology: CBC with absolute neutrophil count and platelets

Acupressure Diary (see Appendix J)
o
Assessment of self-administered acupressure will be reviewed on day 1 of cycle 2 and each subsequent 
cycle. Patients who complete <50% of the prescribed acupressure regimen will be re-educated at cycle 2 on 
appropriate execution of the recommended acupressure regimen.

Clinical AE attribution
o
CTCAE version 5.0
10.2 Quality of Life Assessments
These will be administered at baseline, 6 weeks, and 12 weeks. If a patient is receiving chemotherapy on the day of the 
assessments, the assessments must be completed before the chemotherapy treatment is administered.
At each time point the EORTC QLQ CIPN-20 (see Appendix D) will be used to assess neuropathy and targeted questions from 
the NCI-PRO CTCAE (Appendix E) for the assessment of fatigue, nausea, and anxiety. The Brief Pain Inventory (Appendix F) 
will be used to assess pain. An oral symptoms questionnaire (Appendix G) will be used to assess oral dysesthesia.
On cycle 4 day 8 (±2 days), a mid-cycle assessment will be done for the EORTC-QLQ CIPN-20, NCI-PRO CTCAE, and BPI. This 
may be administered by phone, on paper and returned at next clinic appointment, or electronically.
10.3 Neuropathic Assessments
These will be administered at baseline, 6 weeks, and 12 weeks. If a patient is receiving chemotherapy on the day of the 
assessments, the assessments must be completed before the chemotherapy treatment is administered.
10.3.1 Neuropen
The Neuropen is used to assess sensation with a 10g monofilament on one end and 40g Neurotip on the other end. For each 
patient evaluation, a 10-point examination of the dominant foot will be performed. After 100 such examinations, the 
monofilament needs to be replaced. The Neurotip is single use and must be replaced after each patient examination. A study- 
specific Neuropen will be used for all patient assessments by a trained clinician or research staff member.
Neuropen training will consist first of reviewing the user manual and instructional video for the Neuropen, which 
will follow standard protocols as described for the prior neuropathy trial SWOG 1714 (https://www.swog.org/required- 
s1714-training). Secondly, the staff member will need to be observed by Dr. Greenlee, or another trained member of the 
study team.
Touch and Pressure Perception: Touch and pressure sensation is assessed using the 10-g monofilament in the Neuropen on 
the subject’s dominant foot. The dominant foot can be identified by asking the subject with which foot they would kick a ball. 
The clinician will follow the subsequent steps using the subject’s dominant foot:
1.
Ask the subject to remove sock and/or shoe on the dominant foot and lay flat or sit up on an examination table.
2.
Fully extend the monofilament by sliding the button to the end of the device until a click is heard.
3.
Wipe the end of the monofilament with an alcohol wipe or antiseptic solution.
10.0 SUBJECT EVALUATION
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 14 of 44
Version 9, 19May2023 
4.
The 10 sites in the below figure (Figure 7.1) are to be tested at random on the dominant foot. Press the monofilament 
at a 90-degree angle to the skin surface and increase the pressure until it bows. The subject should not be able to 
see which site is being tested.
5.
Hold in position for 1-2 seconds.
6.
For each of the 10 sites tested, ask the subject if he/she can detect pressure applied from monofilament and name 
the location of sensation. Subjects may use the unmarked picture of the feet (similar to what is shown in Appendix
H) to point to the location of sensation if they are unable to adequately name the location. Record subject response 
for each site tested.
Protective Pain and Sharpness Sensation: This is a calibrated and sterile pain/sharpness test on the subject’s dominant foot. 
The spring mechanism is calibrated to exert a force of 40 grams to help identify subjects with a loss of pain sensation. The 
dominant foot can be identified by asking the subject with which foot they would kick a ball. The clinician will follow the 
subsequent steps using the subject’s dominant foot:
1.
Ask the subject to remove sock and/or shoe on the dominant foot and lay flat or sit up on an examination table.
2.
Take an unused Neurotip and hold by the cap. Do not use if Neurotip cap has previously been removed.
3.
Press Neurotip firmly down into the Neurotip carrier of the Neuropen as far as it will go and clicks into position. The 
Neurotip is correctly positioned when only one chevron can be seen on the Neurotip.
4.
To expose the sterile semi-sharp tip, place thumb gently over the Neurotip pressure gauge and remove Neurotip cap 
by twisting and pulling outwards.
5.
The 10 sites in the below figure (Figure 7.1) are to be tested at random. Press the Neurotip against the skin surface 
at a 90-degree angle. The subject should not be able to see which site is being tested.
6.
Hold in position for 1-2 seconds before removing, taking care to depress within the 40-gram marked white area.
7.
For each of the sites tested, ask the subject if they detect a sharp sensation and name the location of sharp sensation. 
Subjects may use the unmarked picture of the feet (similar to what is shown in Appendix H) to point to the location 
of sensation if they are unable to adequately name the location. Record subject response for each site tested.
8.
Remove and discard the used Neurotip in an appropriate sharps container after completing the 10 site examinations.
10.3.2 Tuning fork
A study-specific 128-Hz tuning fork will be used to assess sensation by a trained clinician or research staff member. As above, 
this will consist first of reviewing the user manual and instructional video for the tuning fork, which will follow standard 
protocols as described for the prior neuropathy trial SWOG 1714 (https://www.swog.org/required-s1714-training). Secondly, 
the staff member will need to be observed by Dr. Greenlee, or another trained member of the study team.
Dominant Lower Extremity Vibration Sensation Testing
1.
The tuning fork should be firmly tapped on the palm of the hand of the clinician to initiate vibration.
2.
The vibrating tuning fork is first placed on the interphalangeal joint of the great toe of the dominant foot (Appendix 
I [A]). The dominant foot can be identified by asking the subject with which foot they would kick a ball. A timer is 
started once the vibrating tuning fork is placed on the interphalangeal joint of the great toe of the dominant foot.
3.
The patient is instructed to report when vibration is no longer detected. The time at which the vibration is no longer 
detected should be noted.
4.
If the patient feels the vibration for 15 seconds or longer, this is defined as normal and should be recorded as such. 
If vibration sensation is normal at the great toe, additional assessments of the lower extremity are not needed.
5.
If vibration sensation in the great toe of the dominant foot is less than 15 seconds, this is defined as absent or 
decreased vibration sensation and should be recorded as such. If vibration sensation is absent or decreased in the 
interphalangeal joint of the great toe of the dominant foot, the clinician then conducts the testing at all additional 
sites listed below on the dominant side. For each site tested, the tuning fork should be firmly tapped on the palm of 
the hand of the clinician to initiate vibration and the vibrating tuning fork is placed on the site. Once the vibrating 
tuning fork is placed on the testing site, a timer is started to measure the time at which the vibration is no longer 
detected. This time should be noted for each site.
a.
The middorsal foot (Appendix I [B]): If the patient feels the vibration for 15 seconds or longer, this is defined 
as normal. If the patient feels the vibration less than 15 seconds, this is defined as absent or decreased 
vibration sensation.
b.
The medial malleolus (ankle) (Appendix I [C]): If the patient feels the vibration for 15 seconds or longer, this 
is defined as normal. If the patient feels the vibration less than 15 seconds, this is defined as abnormal.
c.
The midfibular region of the dominant lower extremity (Appendix I [D]): If the patient feels the vibration for 
15 seconds or longer, this is defined as normal. If the patient feels the vibration less than 15 seconds, this 
is defined as absent or decreased vibration sensation.
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 15 of 44
Version 9, 19May2023 
d.
The patellar region of the dominant lower extremity (Appendix I [E]): If the patient feels the vibration for 
10 seconds or longer, this is defined as normal. If the patient feels the vibration less than 10 seconds, this 
is defined as absent or decreased vibration sensation.
Dominant upper extremity vibration sensation testing
1.
The clinician will conduct the testing at all three sites below on the dominant upper extremity. The dominant upper 
extremity can be identified by asking the subject with which hand they write.
2.
For each site tested, the tuning fork should be firmly tapped on the palm of the hand of the clinician to initiate 
vibration and the vibrating tuning fork is placed on the site. Once the vibrating tuning fork is placed on the testing 
site, a timer is started to measure the time at which the vibration is no longer detected. This time should be noted 
for each site. The three sites to be tested on the dominant upper extremity vibrating tuning fork are:
a.
The distal interphalangeal joint of the index finger (Appendix I [F]): If the patient feels the vibration for 25 
seconds or longer, this is defined as normal. If the patient feels the vibration less than 25 seconds, this is 
defined as absent or decreased vibration sensation. Regardless of sensation at site (a), all three upper 
extremity sites will be tested.
b.
The ulnar styloid (wrist) (Appendix I [G]): If the patient feels the vibration for 15 seconds or longer, this is 
defined as normal. If the patient feels the vibration less than 15 seconds, this is defined as absent or 
decreased vibration sensation.
c.
The lateral epicondyle (elbow) (Appendix I [H]): If the patient feels the vibration for 15 seconds or longer, 
this is defined as normal. If the patient feels the vibration less than 15 seconds, this is defined as absent or 
decreased vibration sensation.
10.4 Acupuncture Expectancy Scale
During the screening period (and prior to randomization), participants will be queried regarding their expectations regarding 
the effects of acupuncture using the validated Acupuncture Expectancy Scale.24 In order to not bias results due to knowledge 
of randomization assignment, this measure will be assessed prior to randomization in all study participants.
Subjects may be removed from this study at any time at their discretion. Subjects may also be removed from this protocol 
if they develop any untoward side effects from the study procedures (acupuncture).
If a subject withdraws consent to participate in the study or aspects of the study, attempts should be made to obtain 
permission to record survival data up to the protocol-described end of the subject follow-up period. Documentation in the 
medical record should state that the subject is withdrawing from the study and what, if any, selected data the subject will 
permit the investigator to obtain.
If a subject withdraws consent and has received less than 1 cycle of chemotherapy with associated study-specified 
treatment (including any planned acupuncture sessions for that cycle), an additional patient will be recruited. Patients who 
receive less than 1 cycle of chemotherapy will not be followed.
An explanation for discontinuing treatment is recorded for each subject discontinuing treatment on the appropriate 
CRF/eCRF. The PI must be notified immediately if a subject discontinues treatment. All subjects, irrespective of treatment 
status, will continue to be followed for survival. Treatment in this study must be discontinued for any of the following 
reasons:

at Investigator’s discretion;

at the subject’s request;

if the subject enrolls in a trial of another investigational agent which does not permit concurrent treatment;

if the patient misses both acupuncture sessions from cycle 1 of chemotherapy;

Grade 4 or life-threatening toxicity (See Section 13, Adverse Events) attributable to the study intervention;

change in chemotherapy regimen which no longer includes oxaliplatin;

pregnancy.
If a patient discontinues use of oxaliplatin, he/she may continue to receive acupuncture either weekly or as protocolized 
(twice weekly every other week) until the completion of 3 months duration of acupuncture treatment.
11.0 SUBJECT DISCONTINUATION OF ACTIVE TREATMENT
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 16 of 44
Version 9, 19May2023 
Medications taken at baseline will be recorded in the source and in CRF. 
Concomitant medication limitations are described in section 9.5
13.1 Adverse Event
According to ICH guidelines (Federal Register. 1997; 62(90):25691-25709) and 21 CFR 312.32, IND Safety Reports, and ICH 
E2A, Definitions and Standards for Expedited Reporting, an adverse event is defined as follows:
An adverse event is any untoward medical occurrence in a clinical investigation subject administered a medicinal product and 
which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the medicinal product.
Abnormal laboratory values for laboratory parameters specified in the study should not be recorded as an adverse event 
unless an intervention is required (repeat testing to confirm the abnormality is not considered intervention), the laboratory 
abnormality results in a serious adverse event or the adverse event results in study termination or 
interruption/discontinuation of study treatment.
Medical conditions present at screening (i.e., before the study treatment is administered) are not adverse events and should 
not be recorded on adverse event pages of the CRFs. These medical conditions should be adequately documented on the 
subject chart. However, medical conditions present at baseline that worsen in intensity or frequency during the treatment or 
post-treatment periods should be reported and recorded as adverse events.
13.2 Serious Adverse Event
An adverse event should be classified as an SAE if it meets one of the following criteria:
Fatal
Adverse event results in death.
Life threatening:
The adverse events placed the subject at immediate risk of death. This classification 
did not apply to an adverse event that hypothetically might cause death if it were 
more severe.
Hospitalization:
It required or prolonged inpatient hospitalization. Hospitalizations for elective medical 
or surgical procedures or treatments planned before enrollment in the treatment plan 
or routine check-ups are not SAEs by this criterion. Admission to a palliative unit or 
hospice care facility is not considered to be a hospitalization.
Disabling/incapacitating
Resulted in a substantial and permanent disruption of the subject’s ability to carry out
normal life functions.
Congenital anomaly or birth 
defect:
An adverse outcome in a child or fetus of a subject exposed to the molecule or 
treatment plan regimen before conception or during pregnancy.
Medically significant:
The adverse event did not meet any of the above criteria but could have jeopardized 
the subject and might have required medical or surgical intervention to prevent one 
of the outcomes listed above.
13.3 Unexpected Adverse Event
An unexpected adverse event is defined as an event that has a nature or severity, or frequency that is not consistent with the 
known risks of acupuncture of acupressure, or the prior medical condition of the subject or other treatment given to the 
subject. “Unexpected,” as used in this definition, refers to an adverse experience that has not been previously observed and 
reported in preclinical or clinical studies of acupuncture and acupressure.
12.0 CONCOMITANT MEDICATIONS
13.0 ADVERSE EVENTS
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 17 of 44
Version 9, 19May2023 
13.4 Monitoring and Recording Adverse Events
All AEs will be assessed by the investigator or qualified designee and recorded in the CRFs. The investigator should attempt 
to establish a diagnosis of the event on the basis of signs, symptoms and/or other clinical information. In such cases, the 
diagnosis should be documented as the adverse event and/or serious adverse event and not described as the individual signs 
or symptoms. The following information should be recorded:

Description of the adverse event using concise medical terminology

Description as to whether or not the adverse event is serious, noting all criteria that apply

The start date (date of adverse event onset)

The stop date (date of adverse event resolution)

The severity (grade) of the adverse event

A description of the potential relatedness of the adverse event to a study procedure or other causality

The action taken due to the adverse event

The outcome of the adverse event
13.5 Grading Adverse Event Severity
All AEs will be graded in severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. 
If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: Grade 1 (mild), Grade 2 (moderate), 
Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal) to describe the maximum intensity of the adverse event.
13.6 Attribution of an Adverse Event
Association or relatedness to the study agent will be assessed by the investigator as follows:

Definite: The event follows a reasonable temporal sequence from exposure to the investigational procedure, has 
been previously described in association with the investigational procedure, and cannot reasonably be attributed 
to other factors such as the subject’s clinical state, other therapeutic interventions or concomitant medications; 
AND the event disappears or improves with withdrawal of the investigational procedure and/or re-appears on re- 
exposure.

Probable: The event follows a reasonable temporal sequence from exposure to the investigational procedure and 
has been previously been described in association with the investigational procedure OR cannot reasonably be 
attributed to other factors such as the subject’s clinical state, other therapeutic interventions or concomitant 
medications.

Possible: The event follows a reasonable temporal sequence from exposure to the investigational procedure, but 
could be attributable to other factors such as the subject’s clinical state, other therapeutic interventions or 
concomitant medications.

Unlikely: Toxicity is doubtfully related to the investigational procedures(s). The event may be attributable to other
factors such as the subject’s clinical state, other therapeutic interventions or concomitant medications.

Unrelated: The event is clearly related to other factors such as the subject’s clinical state, other therapeutic
interventions or concomitant medications.
For general AE assessment, an AE is considered related if it is assessed as definitely, probably, or possibly related; unrelated 
if it is assessed as unlikely related or unrelated.
13.7 Adverse Event Recording Period
AEs will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to acupuncture. 
AEs with an onset date prior to the first exposure to an investigational procedure will not be recorded, except in the case of 
clinically significant worsening of the AE during the specified AE monitoring time frame.
13.8 Adverse Event Reporting Requirements
The investigator or designee must report events to the Fred Hutch IRB in accordance with the policies of the IRB.
Institutional support of trial monitoring will be in accordance with the Fred Hutch/University of Washington Cancer 
Consortium Institutional Data and Safety Monitoring Plan (DSMP). Under the provisions of this plan, Fred Hutch Clinical 
Research Support (CRS) coordinates data and compliance monitoring conducted by consultants, contract research
14.0 DATA AND SAFETY MONITORING PLAN
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 18 of 44
Version 9, 19May2023 
organizations, or Fred Hutch employees unaffiliated with the conduct of the study. Independent monitoring visits occur at 
specified intervals determined by the assessed risk level of the study and the findings of previous visits per the institutional 
DSMP.
In addition, protocols are reviewed at least annually and as needed by the Consortium Data and Safety Monitoring Committee 
(DSMC), Fred Hutch Scientific Review Committee (SRC) and the Fred Hutch/University of Washington Cancer Consortium 
Institutional Review Board (IRB). The review committees evaluate accrual, adverse events, stopping rules, and adherence to 
the applicable data and safety monitoring plan for studies actively enrolling or treating subjects. The IRB reviews the study 
progress and safety information to assess continued acceptability of the risk-benefit ratio for human subjects. Approval of 
committees as applicable is necessary to continue the study.
The trial will comply with the standard guidelines set forth by these regulatory committees and other institutional, state, and 
federal guidelines.
The investigator will ensure that data collected conform to all established guidelines. Each subject is assigned a unique subject 
number to protect subject confidentiality. Subjects will not be referred to by this number, by name, or by any other individual 
identifier in any publication or external presentation. The licensed medical records department, affiliated with the institution 
where the subject receives medical care, maintains all original inpatient and outpatient chart documents.
16.1 Study Design
This is a randomized, controlled feasibility trial of acupuncture treatment delivered during planned chemotherapy infusion 
and 5-FU pump disconnect appointments, and self-administered acupressure plus oral cryotherapy compared to oral 
cryotherapy alone for prevention of CIPN.
16.2 Primary/Secondary Endpoints and Analytical Methods
16.2.1 Primary Endpoint
The primary endpoint is CIPN as measured by the EORTC-CIPN-20.
16.2.2 Secondary Endpoints

Incidence of grade 2 or higher CIPN as measured by CTCAE version 5

Severity of CIPN as measured by a Neuropen and tuning fork.

Proportion of patients assigned to the intervention arm who complete 60% of acupuncture treatments.

Incidence of pain, fatigue, nausea, and anxiety as measured by patient-reported (NCI PRO-CTCAE, BPI, oral 
dysesthesia) and provider-assessed (CTCAE version 5) grading scales.
16.3 Sample Size and Power
This is a pilot study in which preliminary estimates of CIPN severity will be obtained under two treatment conditions. 
Complete data from 50 patients will provide 80% power to detect a difference in EORTC-CIPN-20 of 0.7 standard deviation 
units, based on a t-test with 1-sided alpha=0.05. To account for 10% potential loss to follow-up, we will enroll 56 patients, 28 
on the intervention arm of acupuncture/acupressure and 28 on the standard-of-care arm. Patients who enroll, but are not 
treated, or received less than one cycle of chemotherapy with associated study-specific treatment (including any planned 
acupuncture sessions for that cycle), may be replaced as detailed in section 11.0.
16.4 Randomization
Patients will be randomized 1:1 between the intervention arm and control arm.
16.5 Statistical Analysis
Severity of CIPN (EORTC-CIPN-20 score) at 3 months will be summarized for each treatment arm, and treatment comparisons 
made via linear regression model with adjustment for baseline severity level. Adherence to acupuncture treatment among 
patients in the intervention arm will be described as a proportion with 95% confidence interval. Reasons for treatment non- 
adherence and delivered dose intensity of chemotherapy will be noted. Incidences of CIPN (grade 2 or higher), pain, fatigue,
15.0 DATA MANAGEMENT/CONFIDENTIALITY
16.0 STATISTICAL CONSIDERATIONS
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 19 of 44
Version 9, 19May2023 
nausea, and anxiety will be compared between treatment arms using Chi-squared or Fisher’s exact tests as appropriate. As
this is a pilot study, we will not have adequate power to adjust for covariates such as age, gender, and existing comorbidities.
16.6 Ethnic and Gender Distribution Chart
Projected Target Accrual
ETHNIC AND GENDER DISTRIBUTION CHART
TARGETED / PLANNED ENROLLMENT: 60
Sex / Gender
Ethnic Category
Females
Males
Total
Hispanic or Latino
2
3
5
Not Hispanic or Latino
21
30
51
Ethnic Category Total of All Subjects*
23
33
56
Racial Categories
American Indian / Alaska Native
0
1
1
Asian
2
4
6
Native Hawaiian or Other Pacific Islander
0
0
0
Black or African American
1
2
3
White
18
23
41
More Than One Race
2
3
5
Racial Categories: Total of All Subjects*
23
33
56
The PI is responsible for the conduct of the clinical trial at the site and is responsible for personally overseeing the treatment 
of all study subjects. The PI must assure that all study site personnel, including sub-Investigators and other study staff 
members, adhere to the study protocol and to all applicable regulations and guidelines regarding clinical trials both during 
and after studycompletion.
All subjects are informed of the nature of the program, its possible hazards, and their right to withdraw at any time, and each 
subject signs a form indicating their consent to participate prior to receiving any study-related procedures (see Appendix B).
18.1 Pre-Study Documentation
The following documentation will be filed prior to initiation of the trial: curricula vitae of the PI and all Sub-Investigators; copy 
of the correspondence from the IRB/EC indicating approval of the protocol and Informed Consent Forms, signed by the IRB/EC 
chairperson or designee; an IRB/EC membership list containing the names and occupations of the IRB/EC members; copy of 
the Informed Consent Forms that were reviewed and approved by the IRB/EC.
18.2 Study Site Training
Before initiation of the study, the PI or her designated representatives will review and discuss the following items with the 
Investigator and clinic staff: the protocol, study procedures, record keeping and administrative requirements, drug 
accountability, AE reporting, Good Clinical Practice guidelines, CRF/eCRF completion guidelines, monitoring requirements, 
and the ability of the site to satisfactorily complete the protocol. Additional documents with instructions for study compliance 
and CRF/eCRF completion will be provided.
17.0 INVESTIGATOR OBLIGATIONS
18.0 ADMINISTRATIVE AND REGULATORY CONSIDERATIONS
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 20 of 44
Version 9, 19May2023 
18.3 Documentation
The PI and study staff will maintain a comprehensive and centralized filing system containing all study-related documentation. 
These files must be suitable for inspection by any applicable regulatory agencies/competent authorities at any time, and 
should consist of the following elements: subject files (complete medical records, laboratory data, supporting source 
documentation, and the Informed Consent); study files (the protocol with all amendments, copies of all pre-study 
documentation, and all correspondence between the Competent Authorities, IRB/EC, etc.).
18.4 Access to Source Data
The PI will permit applicable regulatory authorities to monitor the study as needed. The CRF/eCRF and related source 
documents will be reviewed in detail by applicable regulatory authorities as needed. Only original source documents are 
acceptable for review. This review includes inspection of data acquired as a requirement for participation in this study and 
other medical records as required to confirm information contained in the CRF/eCRF, such as past history, secondary 
diagnoses, and concomitant medications. Other study records, such as correspondence with Competent Authorities, and 
IRB/EC and screening logs will also be inspected. All source data and study records must also be available for inspection by 
representatives of regulatory agencies.
18.5 Data Collection
Data will be collected and stored in an electronic database. Any changes or corrections made to the CRF/eCRF must be 
subsequently reviewed and signed by the PI. All data fields in the CRF/eCRF must be completed.
18.6 Protocol Interpretation and Compliance
The procedures defined in the protocol are carefully reviewed by the PI and his/her staff prior to the time of study initiation 
to ensure accurate representation and implementation. Protocol amendments, if any, are reviewed and implemented 
promptly following IRB/EC and relevant Competent Authorities approval.
18.7 Disclosure of Data/Publication
Individual subject medical information obtained as a result of this study is considered confidential and disclosure to third 
parties other than those noted below is prohibited. Such medical information may be given to the subject’s personal physician 
or to other appropriate medical personnel responsible for the subject’s welfare. Data generated as a result of this study are 
to be available for inspection on request by regulatory agencies, the Sponsor or its designee and by the IRB/EC. It is anticipated 
that the final results of this study will be submitted to a peer-reviewed scientific journal. Authorship on such a paper will be 
acknowledged with customary scientific practice.
18.8 Ethical Considerations
The Investigator agrees to conduct this study in accordance with applicable United States FDA clinical trial regulations and 
guidelines, applicable United States FDA clinical trial regulations and guidelines, the ICH (E6) GCP guidelines, the IRB/EC and 
local legal requirements and with the Declaration of Helsinki (1989). The Investigator will conduct all aspects of this study in 
accordance with all national, state, and local laws of the applicable regulatory agencies.
18.9 Informed Consent
The PI assumes the responsibility of obtaining written Informed Consent for each subject or the subject’s legally authorized 
representative before any study-specific procedures are performed. Subjects meeting the criteria set forth in the protocol 
will be offered the opportunity to participate in the study. To avoid introduction of bias, the Investigator must exercise no 
selectivity with regard to offering eligible subjects the opportunity to participate in the study. Subjects or parents/legal 
guardians of all candidate subjects will receive a comprehensive explanation of the proposed treatment, including the nature 
of the therapy, alternative therapies available, any known previously experienced adverse reactions, the investigational status 
of the study treatment, and other factors that are part of obtaining a proper Informed Consent. Subjects will be given the 
opportunity to ask questions concerning the study, and adequate time to consider their decision to or not to participate.
Informed Consent will be documented by the use of a written Consent Form that includes all the elements required 
by FDA regulations and ICH guidelines. The form is to be signed and dated by the subject or subject's legally authorized 
representative and by the person who administers the consent process. A copy of the signed form will be given to the person 
who signed it, the original signed Consent Form will be filed with the subject’s medical records, and copy maintained with the 
subject’s study records. The date and time of time of the Informed Consent must be recorded in the source documents.
If an amendment to the protocol changes the subject participation schedule in scope or activity, or increases the 
potential risk to the subject, the Informed Consent Form must be amended. Any amended Informed Consent must be
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 21 of 44
Version 9, 19May2023 
approved by the IRB/EC prior to use. The revised Informed Consent Form must be used to obtain re-consent from any subjects 
currently enrolled in the study if the subject is affected by the amendment, and must be used to document consent from any 
new subjects enrolled after the approval date of the amendment.
18.10
Institutional Review Board/Ethics Committee
The PI will assure that an appropriately constituted IRB/EC that complies with the requirements of 21 CFR Section 56 or 
written assurance of compliance with ICH (E6) guidelines will be responsible for the initial and continuing review and approval 
of the clinical study. Before initiation of the study, the PI or designee will forward copies of the protocol and Consent Form 
to be used for the study to the IRB/EC for its review and approval.
The PI or designee will also assure that all changes in the research activity and all unanticipated problems involving 
risks to human subjects or others will be reported promptly to the IRB/EC, and that no changes will be made to the protocol 
without prior Sponsor and IRB/EC approval, except where necessary to eliminate apparent immediate hazards to human 
subjects.
The Investigator or designee will be responsible for submitting periodic progress reports to the IRB/EC at intervals 
appropriate to the degree of subject risk involved in the study, but not less than once per year and at the completion or 
termination of the study.
18.11
Subject Privacy
The Investigators affirm and uphold the principle of the subject's right to privacy. The Investigators shall comply with 
applicable national and local privacy laws.
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 22 of 44
Version 9, 19May2023 
1.
André T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as 
adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. Jul 2009;27(19):3109-16. 
doi:10.1200/JCO.2008.20.6771
2.
Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J 
Med. May 2011;364(19):1817-25. doi:10.1056/NEJMoa1011923
3.
Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N 
Engl J Med. 12 2018;379(25):2395-2406. doi:10.1056/NEJMoa1809775
4.
Saif MW, Reardon J. Management of oxaliplatin-induced peripheral neuropathy. Ther Clin Risk Manag. Dec 
2005;1(4):249-58.
5.
Hershman DL, Lacchetti C, Dworkin RH, et al. Prevention and management of chemotherapy-induced peripheral 
neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. Jun 
2014;32(18):1941-67. doi:10.1200/JCO.2013.54.0914
6.
Loprinzi CL, Qin R, Dakhil SR, et al. Phase III randomized, placebo-controlled, double-blind study of intravenous 
calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance). J Clin Oncol. Apr 
2014;32(10):997-1005. doi:10.1200/JCO.2013.52.0536
7.
Bauman B, Mick R, Martinez E, et al. Efficacy of Oral Cryotherapy During Oxaliplatin Infusion in Preventing Oral 
Thermal Hyperalgesia: A Randomized Trial. J Natl Compr Canc Netw. Apr 2019;17(4):358-364. doi:10.6004/jnccn.2018.7110
8.
Liang F, Chen R, Cooper EL. Neuroendocrine mechanisms of acupuncture. Evid Based Complement Alternat Med. 
2012;2012:792793. doi:10.1155/2012/792793
9.
Litscher G. Bioengineering assessment of acupuncture, Part 6: monitoring--neurophysiology. Crit Rev Biomed Eng. 
2007;35(1-2):1-36. doi:10.1615/critrevbiomedeng.v35.i1-2.10
10.
Derksen TM, Bours MJ, Mols F, Weijenberg MP. Lifestyle-Related Factors in the Self-Management of 
Chemotherapy-Induced Peripheral Neuropathy in Colorectal Cancer: A Systematic Review. Evid Based Complement Alternat 
Med. 2017;2017:7916031. doi:10.1155/2017/7916031
11.
Hsieh YL, Chou LW, Hong SF, et al. Laser acupuncture attenuates oxaliplatin-induced peripheral neuropathy in 
patients with gastrointestinal cancer: a pilot prospective cohort study. Acupunct Med. Oct 2016;34(5):398-405. 
doi:10.1136/acupmed-2016-011112
12.
Chien TJ, Liu CY, Fang CJ, Kuo CY. The Efficacy of Acupuncture in Chemotherapy-Induced Peripheral Neuropathy: 
Systematic Review and Meta-Analysis. Integrative cancer therapies. Jan-Dec 2019;18:1534735419886662. 
doi:10.1177/1534735419886662
13.
Li K, Giustini D, Seely D. A systematic review of acupuncture for chemotherapy-induced peripheral neuropathy.
Current oncology. Apr 2019;26(2):e147-e154. doi:10.3747/co.26.4261
14.
Lu W, Giobbie-Hurder A, Freedman RA, et al. Acupuncture for Chemotherapy-Induced Peripheral Neuropathy in 
Breast Cancer Survivors: A Randomized Controlled Pilot Trial. The oncologist. Oct 14 2019;doi:10.1634/theoncologist.2019- 
0489
15.
Greenlee H, Crew KD, Capodice J, et al. Methods to Standardize a Multicenter Acupuncture Trial Protocol to 
Reduce Aromatase Inhibitor-related Joint Symptoms in Breast Cancer Patients. J Acupunct Meridian Stud. Jun 
2015;8(3):152-8. doi:10.1016/j.jams.2015.03.006
16.
Zick SM, Sen A, Hassett AL, et al. Impact of Self-Acupressure on Co-Occurring Symptoms in Cancer Survivors. JNCI 
Cancer Spectr. Nov 2018;2(4):pky064. doi:10.1093/jncics/pky064
17.
Lyman GH, Greenlee H, Bohlke K, et al. Integrative Therapies During and After Breast Cancer Treatment: ASCO 
Endorsement of the SIO Clinical Practice Guideline. J Clin Oncol. 09 2018;36(25):2647-2655. doi:10.1200/JCO.2018.79.2721
18.
Peoples AR, Culakova E, Heckler CE, et al. Positive effects of acupressure bands combined with relaxation 
music/instructions on patients most at risk for chemotherapy-induced nausea. Support Care Cancer. Dec 2019;27(12):4597- 
4605. doi:10.1007/s00520-019-04736-x
19.
Lin L, Zhang Y, Qian HY, et al. Auricular acupressure for cancer-related fatigue during lung cancer chemotherapy: a 
randomised trial. BMJ Support Palliat Care. Dec 2019;doi:10.1136/bmjspcare-2019-001937
20.
Yeh CH, Lukkahatai N, Campbell C, et al. Preliminary Effectiveness of Auricular Point Acupressure on 
Chemotherapy-Induced Neuropathy: Part 2 Laboratory-Assessed and Objective Outcomes. Pain Manag Nurs. Dec 
2019;20(6):623-632. doi:10.1016/j.pmn.2019.04.004
21.
He Y, Guo X, May BH, et al. Clinical Evidence for Association of Acupuncture and Acupressure With Improved 
Cancer Pain: A Systematic Review and Meta-Analysis. JAMA Oncol. Dec 2019;doi:10.1001/jamaoncol.2019.5233
22.
Deadman P, Al-Khafaji M, Baker K. A Manual of Acupuncture. 1998:256-325.
19.0 REFERENCES
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 23 of 44
Version 9, 19May2023 
23.
National Acupuncture Foundation. Clean Needle Technique Manual for Acupuncturists: Guidelines and Standards 
for the Clean and Safe Clinical Practice of Acupuncture. 2003;
24.
Mao JJ, Xie SX, Bowman MA. Uncovering the expectancy effect: the validation of the acupuncture expectancy 
scale. Altern Ther Health Med. 2010 Nov-Dec 2010;16(6):22-7.
Appendix A:
ECOG Performance Status Scale 
Appendix B:
Study Calendar
Appendix C:
Location of Acupuncture and Acupressure Points 
Appendix D:
EORTC QLQ CIPN-20
Appendix E:
NCI PRO-CTCAE 
Appendix F:
Brief pain inventory
Appendix G:
Oral symptoms questionnaire 
Appendix H:
Neuropen Assessment Points 
Appendix I:
Tuning Fork Assessment Points 
Appendix J:
Acupressure Diary
Appendix K:
Acupuncture Expectancy Scale 
Appendix L:
Acupressure Ear Seed Care Instructions 
Appendix M:
Waitlist Acupuncture Voucher
Appendix N:
Research Acupuncture Appointments in the Wellness Clinic 
Appendix O:
Cryotherapy Phone Script
Appendix P:
Cryotherapy Questionnaire
20.0 APPENDICES
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 24 of 44
Version 9, 19May2023 
20.1 APPENDIX A: ECOG Performance Status Scale
ECOG Performance Status Scale
GRADE
SCALE
0
Fully active, able to carry out all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary 
nature, e.g., light housework, office work
2
Ambulatory and capable of all self-care but unable to carry out work activities. Up and about more than 50% of 
waking hours.
3
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
4
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
5
Dead
Fred Hutch IRB
Approved 
6/27/2023

Page 25 of 44
Version 9, 19May2023
RG1121095
20.2 APPENDIX B: Study Calendar
Study Calendar
Cycle 1
Cycles 2-36
Cycle 46
Cycles 5-66
Procedure
Screening
within 14
days
Day 1
Day 3
Day 1
Day 3
Day 1
Day 3
Day 8
± 2
days
Day 1
Day 3
End of Tx7
Waitlist control visit8
Physical Exam1
X
X
X
X
X
X
X
Medical History
X
X
X
X
X
X
Pregnancy Test
X
CBC2
X
X
X
X
X
Oxaliplatin-based chemotherapy
X
X
X
X
Acupuncture treatment
X3
X3
X3
X3
X3
X3
X3
X3
X
Acupressure training3,4
X
X
X
Acupressure diary review
X
X
X
X
Cryotherapy
X
X
X
X
AE Assessment
X
X
X
X
X
X9
PROs5
X
X
X
Neuropen, tuning fork
X
X
X
Acupuncture Expectancy Scale
X
X5
1 On day 3, only vital signs are needed (a complete physical exam is not required). For waitlist control visits, this will include notation of pulse, tongue color, and any other 
findings considered notable to the acupuncturist
2 Labs may be obtained up to 3 days prior. If lab values are below the accepted treatment thresholds, they must be repeated and above treatment parameters before 
treatment delivery.
3 Patients in Arm A (intervention arm) only
4 Acupressure retraining will be completed at the cycle 2, day 1 visit if a patient has completed <50% of the prescribed regimen
5 PROs for all time points: EORTC QLQ CIPN-20, NCI-PRO CTCAE, BPI, oral symptoms. At C4D8, a sub-set of the PROs will be re-administered: EORTC QLQ CIPN-20, NCI-PRO 
CTCAE, BPI
6 Study procedures will be timed with patient chemotherapy. If chemotherapy is delayed, then the acupuncture, acupressure, and standard-of-care treatments will be 
delayed accordingly.
7 See section 9.9 for a description of the permitted time range for the EOT visit.
8 Patients in Arm B (control arm) only
9 Limited AE assessment of acupuncture-associated toxicities (bruising, bleeding, pain, other) will be assessed, as well as chief complaint, and any other major considerations 
for the acupuncturist.

RG1121095
Page 26 of 44
Version 9, 19May2023
20.3 APPENDIX C: Location of Acupuncture and Acupressure Points
Location of acupuncture points. All points needled bilaterally (except midline points)
Day 1 Acupuncture Protocol
Day 3 Acupuncture Protocol
Location of acupressure points. All points pressured bilaterally (except midline GV20)
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 27 of 44
Version 9, 19May2023
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 28 of 44
Version 9, 19May2023
20.4 APPENDIX D: EORTC QLQ CIPN-20
EORTC QLQ – CIPN20
Patients sometimes report that they have the following symptoms or problems. Please indicate 
the extent to which you have experienced these symptoms or problems during the past week. 
Please answer by circling the number that best applies to you.
Not 
at 
all
A
little
Quite 
a bit
Very 
much
During the past week
1. Did you have tingling fingers or hands?
1
2
3
4
2. Did you have tingling toes or feet?
1
2
3
4
3. Did you have numbness in your fingers or hands?
1
2
3
4
4. Did you have numbness in your toes or feet?
1
2
3
4
5. Did you have shooting or burning pain in your fingers 
or hands?
1
2
3
4
6. Did you have shooting or burning pain in your toes or 
feet?
1
2
3
4
7. Did you have cramps in your hands?
1
2
3
4
8. Did you have cramps in your feet?
1
2
3
4
9. Did you have problems standing or walking because of 
difficulty feeling the ground under your feet?
1
2
3
4
10. Did you have difficulty distinguishing between hot and 
cold water?
1
2
3
4
11. Did you have a problem holding a pen, which made 
writing difficult?
1
2
3
4
12. Did you have difficulty manipulating small objects with 
your fingers (for example, fastening small buttons)?
1
2
3
4
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 29 of 44
Version 9, 19May2023
13. Did you have difficulty opening a jar or bottle because 
of weakness in your hands?
1
2
3
4
During the past week
14. Did you have difficulty walking because your feet 
dropped downwards?
1
2
3
4
15. Did you have difficulty climbing stairs or getting up out 
of a chair because of weakness in your legs?
1
2
3
4
16. Were you dizzy when standing up from a sitting or lying 
position?
1
2
3
4
17. Did you have blurred vision?
1
2
3
4
18. Did you have difficulty hearing?
1
2
3
4
Please answer the following question only if you drive a 
car
19. Did you have difficulty using the pedals?
1
2
3
4
Please answer the following question only if you are a 
man
20. Did you have difficulty getting or maintaining an 
erection?
1
2
3
4
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 30 of 44
Version 9, 19May2023
20.5 APPENDIX E: NCI PRO-CTCAE
NCI PRO-CTCAE
As individuals go through treatment for their cancer they sometimes experience different symptoms and side 
effects. For each question, please select the one response that best describes your experiences over the past 7 
days…
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 31 of 44
Version 9, 19May2023
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 32 of 44
Version 9, 19May2023
20.6 APPENDIX F: Brief Pain Inventory
Brief Pain Inventory
Please rate your pain by circling the one number the best describes your pain at its worst in the last 24 hours 
0
1
2
3
4
5
6
7
8
9
10
No
Pain as bad as
pain
you can imagine
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 33 of 44
Version 9, 19May2023
20.7 APPENDIX G: Oral symptoms questionnaire
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 34 of 44
Version 9, 19May2023
20.8 APPENDIX H: Neuropen Assessment Points
Sites on the feet to be evaluated with Neuropen monofilament and Neurotip
Fred Hutch IRB
Approved 
6/27/2023

A
RG1121095
Page 35 of 44
Version 9, 19May2023
20.9 APPENDIX I: Tuning Fork Assessment Points
Sites on the feet to be evaluated with the tuning fork
   A
   B
   C
   E
D
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 36 of 44
Version 9, 19May2023
Note: The tuning fork is firmly tapped on the palm and then placed on the interphalangeal joint of the great toe 
(A). If vibration sensation is diminished or absent in the great toe, testing should be performed at the middorsal 
foot (B) and the medial malleolus (C), followed by the mid-fibular (D) and patellar (E) regions.
Note: The tuning fork is firmly tapped on the palm and then placed at the distal interphalangeal joint of the index 
finger (F), the ulnar styloid (G), and the lateral epicondyle (H).
F
  G
  H
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 37 of 44
Version 9, 19May2023
20.10
APPENDIX J: Acupressure Diary
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 38 of 44
Version 9, 19May2023
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 39 of 44
Version 9, 19May2023
20.11
APPENDIX K: Acupuncture Expectancy Scale
For each statement, please choose the closest answer
Every individual may have different expectation of the effects of acupuncture. If we use the 
following statements to describe your expectation of acupuncture’s effect on your treatment 
side effects after the entire course of acupuncture therapy, how much do you agree?
Not at all 
agree
Agree a 
little
Moderately 
agree
Mostly 
agree
Completely 
agree
1
My treatment side effects will 
improve a lot.
2
I will be able to cope with my 
treatment side effects better.
3
The symptoms of my
treatment side effects will 
disappear.
4
My energy level will increase.
Acupuncture and 
acupressure during
treatment?
Waitlist, with the option of 
receiving acupuncture after
your treatment is complete?
5
Which of the two treatment 
assignments do you prefer?
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 40 of 44
Version 9, 19May2023
20.12
APPENDIX L: Acupressure Ear Seed Care Instructions
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 41 of 44
Version 9, 19May2023
20.13
APPENDIX M: Waitlist Acupuncture Voucher
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 42 of 44
Version 9, 19May2023
20.14
APPENDIX N: Research Acupuncture Appointments in the Wellness Clinic
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 43 of 44
Version 9, 19May2023
20.15
APPENDIX O: Cryotherapy Phone Script
Fred Hutch IRB
Approved 
6/27/2023

RG1121095
Page 44 of 44
Version 9, 19May2023
20.16
APPENDIX P: Cryotherapy Questionnaire
Fred Hutch IRB
Approved 
6/27/2023