Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Breast Cancer Patients
Phase: NA
Conditions: Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Grade 1 Peripheral Motor Neuropathy, CTCAE, Grade 1 Peripheral Sensory Neuropathy, CTCAE, Grade 2 Peripheral Motor Neuropathy, CTCAE, Grade 2 Peripheral Sensory Neuropathy, CTCAE, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8
Sponsor: Wake Forest University Health Sciences

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page i of 55 
 
Study Chairs: 
 
 
 
  Nancy E. Avis, PhD, Professor 
Social Science & Health Policy 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
Remy Coeytaux, MD, PhD, Professor 
Family and Community Medicine 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
 
Roy Strowd, MD, Assistant Professor 
Neurology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
Alexandra Thomas, MD, FACP, Professor 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
 
Co-Investigators (alphabetical)  Katherine C. Ansley, MD, Assistant Professor 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
 
 
 
 
 
 
 
Michael Cartwright, MD, Associate Professor 
Neurology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page ii of 55 
 
 
Bernard R. Chinnasami, MD 
Hematology and Oncology 
Hayworth Cancer Center 302 Westwood Avenue 
High Point, NC 27262 
 
Vallathucherry C. Harish, MD 
Hematology and Oncology 
Hayworth Cancer Center 302 Westwood Avenue 
High Point, NC 27262 
 
 
Ashlyn Hedgecock, PA-C 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
 
Jason Huff, MD 
Hematology and Oncology 
Hayworth Cancer Center 302 Westwood Avenue 
High Point, NC 27262 
 
 
Toni Lima, PA-C 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
 
Heather Dawn Pacholke, MD, Assistant Professor 
Radiation Oncology 
Hayworth Cancer Center 302 Westwood Avenue 
High Point, NC 27262 
 
Boris Claude Pasche, MD, PhD 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
Caio Max Sao Pedro Rocha Lima, MD, MS 
Section on Hematology and Oncology 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page iii of 55 
 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
George H. Sanders, MD 
Hematology and Oncology 
Hayworth Cancer Center 302 Westwood Avenue 
High Point, NC 27262 
 
Omar P. Sangueza, MD, Professor 
Pathology, WFBMC 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
Yusuke Shiozawa, PhD, Assistant Professor 
Cancer Biology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston Salem, NC 27157 
 
Steven Mark Sorscher, MD, Professor 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
Francis O. Walker, MD, Professor 
Neurology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
Susan Ann Kidwell Williford, MD, Assistant Professor 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
 
 
Shan Wong, PhD, 
Postdoctoral Fellow 
Social Science & Health Policy 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page iv of 55 
 
 
George Yacoub, MD 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
Biostatistician: 
 
 
Janet Tooze, PhD, Professor 
Biostatistical Sciences 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
 
 
Research Nurses: 
Angela Howell 
Wake Forest Baptist Comprehensive Cancer Center 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
Heather Kirby 
Wake Forest Baptist Comprehensive Cancer Center 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
 
Study Coordinator: 
 
Kelsey Shore  
Community Research Coordinator 
Office of Cancer Health Equity 
Wake Forest Baptist Comprehensive Cancer Center 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
Laura Hayes, RN 
High Point Nursing Clinical Research Manager  
Hayworth Cancer Center 302 Westwood Avenue 
High Point, NC 27262 
 
Sheri Whittington 
High Point Oncology Admin 
Hayworth Cancer Center 302 Westwood Avenue 
High Point, NC 27262 
 
Regulatory Contact: 
 
Emily Teal 
Wake Forest Baptist Comprehensive Cancer Center 
Medical Center Blvd 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page v of 55 
 
Winston-Salem, NC 27157 
 
Protocol Editor: 
 
 
Mac Robinson, PhD 
Wake Forest Baptist Comprehensive Cancer Center 
Winston-Salem, NC 27157 
 
Dermatology Pathology  
Fellow:  
 
 
 
 
Christine Ahn, MD 
 
 
 
 
 
 
Winston-Salem, NC 27157 
 
 
 
 
 
 
 
 
 
Participating Institution(s): 
Wake Forest Baptist Medical Center 
 
Version Date: 
 
 
 
10/21/20 
 
Confidential 
 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page vi of 55 
 
 
Table of Contents 
Schema...................................................................................................................................... 1 
1.0 
Introduction and Background .......................................................................................... 2 
2.0 
Objectives ...................................................................................................................... 5 
2.1 Primary Objective .................................................................................................................. 5 
2.2. 
Secondary Objectives .................................................................................................. 6 
2.3. 
Exploratory Objectives ................................................................................................. 6 
3.0 
Study Population ............................................................................................................ 6 
3.1 
Inclusion Criteria .......................................................................................................... 7 
3.2 
Exclusion Criteria ......................................................................................................... 7 
3.3 
Inclusion of women and minorities ............................................................................... 7 
4.0 
Methods ......................................................................................................................... 8 
4.1 
Registration Procedures .............................................................................................. 8 
4.2  Study Activities ..................................................................................................................... 9 
4.3 
Study setting .............................................................................................................. 10 
4.4 
Enrollment and Screening ......................................................................................... 10 
4.5 
Peripheral Nerve Assessment ................................................................................... 11 
4.6 
Randomization........................................................................................................... 12 
4.7 
Intervention: Acupuncture Treatments ....................................................................... 13 
4.8 
Week 12 End of Treatment Assessment .................................................................... 13 
4.9 
Acupuncture for Usual Care Control Group ............................................................... 13 
5.0 
Adverse Events List and Reporting Requirements ...................................................13 
5.1 
Adverse Event List for Acupuncture ...................................................................... 13 
5.2 
Adverse Event List for Nerve Conduction Studies ................................................ 14 
5.3 
Adverse Event List for Biopsies ................................................................................. 14 
5.4 
Adverse Event List for Ultrasound.............................................................................. 14 
5.5 
Adverse Event Characteristics ............................................................................... 14 
5.6 
STRC SAE Reporting Requirements ...................................................................... 14 
5.7 
WFUHS IRB AE Reporting Requirements .............................................................. 15 
6.0 
Duration of Follow-up ....................................................................................................15 
7.0 
Outcome Measures .......................................................................................................16 
7.1 
Primary Outcome ....................................................................................................... 16 
7.2 
Secondary Outcomes ................................................................................................ 16 
7.3 
Covariates ................................................................................................................. 16 
8.0 
Statistical Considerations ..............................................................................................17 
8.1 
Sample Size and Power ............................................................................................ 17 
8.2 
Analysis of Primary Objective .................................................................................... 17 
8.3 
Analysis of Secondary Objectives .............................................................................. 17 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page vii of 55 
 
8.4 
Analyses of Exploratory Outcome .............................................................................. 18 
8.5 
Accrual Rate .............................................................................................................. 18 
8.6 
Length of Study ......................................................................................................... 18 
9.0 
Data Management .........................................................................................................18 
10.0 
Confidentiality and Privacy ............................................................................................19 
11.0 
Data Safety and Monitoring ...........................................................................................19 
12.0 
Reporting of Unanticipated Problems, Adverse Events or Deviations ............................19 
References ...............................................................................................................................20 
Appendix A: Subject Eligibility Checklist ....................................................................................24 
Appendix B: Protocol Registration Form....................................................................................27 
Appendix C - Race & Ethnicity Verification Form .......................................................................28 
Appendix D: Clinical Evaluation from History/Exam ..................................................................29 
Appendix E Patient Reported Outcomes: EORTC QLQ-CIPN20 and PRO-CTCAE ..................34 
Appendix F: Nerve Conduction Study Data Collection Form .....................................................36 
Appendix G: Ultrasound Nerve Diameter Data Form .................................................................37 
Appendix H: Nerve Fiber Density Data Collection Form ............................................................38 
Appendix I: Adverse Events Log ...............................................................................................39 
Appendix J: Follow-up Form for Skin Biopsy .............................................................................40 
Appendix K: Mandatory STRC SAE Reporting Requirements ...................................................41 
Appendix L: Patient Pre-Neuropathy Grading Instructions Card ................................................48 
Appendix M: CTCAE Neuropathy Grading Form .......................................................................49 
Appendix N: Chemotherapy Form .............................................................................................50 
Appendix O: Acupuncture Treatment Summary Form ...............................................................52 
Appendix P: Acupuncture Expectancy Scale............................................................................. 48 
Appendix Q: Action Telephone Screening Form ……………………………………………………49

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 1 of 55 
 
Schema 
 
 
 
 
 
 
 
 
 
 
 
(n=22) 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 2 of 55 
 
1.0 
Introduction and Background 
Peripheral neuropathy (PN) is broadly defined as damage to the peripheral nervous system 
caused by a primary lesion or dysfunction.1 Chemotherapy-induced peripheral neuropathy 
(CIPN) is a common consequence of cytotoxic chemotherapies and results in length-
dependent sensory predominant impairments with symptoms of numbness, tingling, burning 
and pain in hands and feet. CIPN is consistently associated with lower self-reported physical 
function and quality of life and may contribute to increased cancer mortality as patients often 
do not complete their full course of chemotherapy due to dose reductions, modifications, or 
treatment discontinuation. Although the underlying mechanisms of CIPN are only partially 
understood,2 CIPN is a small fiber neuropathy that results in reduced nerve fiber density in the 
skin and can lead to physiologic changes in nerve conduction and anatomic changes in 
peripheral nerve anatomy. CIPN is more prevalent and more severe in African American (A-A) 
compared to women of other races, but the reason for this is not understood.3,4  
 
CIPN is a significant problem for cancer survivors. Prevalence rates of CIPN vary widely based 
on different patient populations, different grading systems and symptom assessments, but 
have been found in up to 80% of patients receiving chemotherapy.5 In fact, CIPN is the most 
common reason for dose reduction in breast cancer patients receiving taxane chemotherapy. 
One study found that 42% of early stage breast cancer survivors had CIPN two years after 
chemotherapy6 and another reported that 50% of women cancer survivors reported symptoms 
of CIPN six years after treatment.7  Similarly, platinum agents including cisplatin, carboplatin, 
and oxaliplatin also commonly result in peripheral neurotoxicity. Transient neurotoxic effects 
are experienced by nearly all patients following oxaliplatin infusion with patients describing cold 
hypersensitivity within hours of infusion. Chronic peripheral neuropathy is estimated to occur in 
up to 70% of patients receiving oxaliplatin. Disruption of calcium signaling leads to axonal 
hyperexcitability and peripheral nerve dysfunction leading to oxaliplatin-induced peripheral 
neuropathy (OIPN).8,9 
 
A recent NCI Symptom Management and Health-related Quality of Life Steering Committee 
symposium concluded that research was needed to understand the mechanisms of CIPN and 
to identify therapies to prevent or treat CIPN.10 This group expressed particular interest in non-
drug interventions. The NCI considers the development of adjuncts for the prevention and 
relief of CIPN as essential for patient care.11  
Acupuncture has been found to effectively treat other types of pain including chronic low-back 
pain, migraine and tension headaches, as well as chemotherapy-induced nausea and 
vomiting.12,13  Acupuncture is a safe, non-toxic treatment that unlike other pharmacologic 
agents that target mechanisms of CIPN does not interfere with chemotherapeutic efficacy. A 
recent systematic review found that acupuncture showed benefit for neuropathy caused by 
diabetes, Bell’s palsy, and carpal tunnel syndrome, and probably for the treatment of HIV- 
related neuropathy (which also causes a severe sensory-predominant polyneuropathy).12 The 
review further concluded that acupuncture appears to improve nerve conduction study 
parameters in both sensory and motor nerves. There were not enough randomized control 
trials [RCTs] for cancer-related neuropathy that met the inclusion criteria to review this 
condition.12 However, two small nonrandomized pilot studies suggest that acupuncture may be 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 3 of 55 
 
effective for reducing CIPN.14,15 These pilot studies support further investigation into how 
acupuncture works and whether patient-reported symptom improvement is associated with 
underlying physiologic changes in the nerve.  
There are strong mechanistic links between acupuncture and CIPN. The dorsal root ganglion 
(DRG) is a critical site for peripheral nerve health and plays an important role in mediating the 
pathologic changes with CIPN and the action of acupuncture. In animal models and human 
studies, acupuncture has been shown to modulate dorsal horn and DRG neurotransmission 
including transmission of opioid, norepinephrine, serotonin, and glutamate signals.16 Cell 
bodies in the DRG lack a blood-nerve barrier and are thus subject to the toxic effects of most 
chemotherapy. Taxane chemotherapies disrupt axonal transport from the DRG and perturb 
normal axonal flow resulting in mitochondrial dysfunction, oxidative stress, and nerve 
swelling.17–20 For oxaliplatin, calcium dysregulation leads to a channelopathy in the terminal 
nerve branches disrupting axoplasmic flow and causing hyperexcitability within the nerve and 
dorsal root. This results in impaired conduction along peripheral sensory nerves as assessed 
by nerve conduction studies (NCS), reduced intraepidermal nerve fiber (IENF) density 
detected by skin biopsy, and emerging evidence of nerve swelling on neuromuscular 
ultrasound. These standard of care tests provide a window into pathologic changes of CIPN 
and the potential effect of acupuncture on peripheral neurotoxicity. The results of this pilot 
study will be applicable to other causes of peripheral neuropathy as there is no compelling 
reason to believe that acupuncture’s mechanisms of action (if proven to be effective) for 
treating CIPN would be different for other etiologies of peripheral neuropathy.  
 
This pilot study seeks to obtain preliminary evidence for the evaluation of acupuncture in 
reducing the severity and/or progression of CIPN due to neurotoxic chemotherapy. We 
hypothesize that acupuncture can improve CIPN and prevent the escalation of CIPN as 
measured by patient–reported outcomes and the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI-CTCAE) Neuropathy Sensory Subscale 
(https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50).  We 
also hypothesize that the reduction in CIPN will allow for patients to continue their course of 
chemotherapy.  We will also investigate whether improving CIPN symptoms is associated with 
improved objective measures of nerve function, which will provide potential mechanisms for 
how acupuncture works in treating PN. We hypothesize that acupuncture’s effect on improving 
self-reported symptoms will be evidenced by improved objective nerve function as assessed 
by nerve conduction studies (NCS), intraepidermal nerve fiber (IENF) density, and/or nerve 
swelling by ultrasound. 
Standard of Care, Objective Assessments of Nerve Function 
CIPN manifests via several different pathophysiological mechanisms that can be assessed by 
currently available standard of care methods including physical examination, nerve conduction 
studies (NCS), skin biopsy to evaluate intraepidermal nerve fiber density (IENF), peripheral 
nerve ultrasound, and patient-reported outcome measures. Each of these studies are standard 
of care for the assessment of sensory-predominant neuropathies such as CIPN. 
Physical Examination: Physical exam with quantitative sensory testing (QST) uses tuning forks 
or monofilaments to objectively measure the sensory threshold for proprioception. QST may be 
a useful addition to self-reported symptoms as it is non-invasive, easily implemented, and well-

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 4 of 55 
 
correlated with self-reported CIPN symptoms. Although promising, it has not been shown to 
provide early detection of subclinical taxane-induced CIPN.22,23  
Patient-Reported Outcome Measures: the European Organization for Research and Treatment 
of Cancer (EORTC) QLQ-CIPN20 Questionnaire is a 20-item self-reported survey that is easy 
to administer and was validated across participants in four large cooperative group trials.24 The 
QLQ-CIPN20 sensory scale has been studied specifically with TIPN among breast cancer 
patients and was shown to be correlated with patient-reported symptoms from the Common 
Toxicity Criteria (0.79, p < 0.00001). Since taxanes and oxaliplatin are not associated with 
hearing loss, that corresponding item was excluded from analysis in that study.25,26  For 
normative comparison, non-cancer patients tend to have very low scores on the QLQ-CIPN20 
with a sum score average of 3.6 (standard deviation 7.2) and subtotals of 3.2 (7.3) for sensory 
measures, 3.8 (9.2) for motor, and 4.4 (10.7) for autonomic. The vast majority of non-cancer 
patients (90.1%) had a sum score of 0-10%; older age and self-reported comorbidities were 
associated with higher QLQ-CIPN20 scores. Based on the results from that study, age-
matched normative data has been generated for the QLQ-CIPN20.27 PRO-CTCAE is an item 
library containing 124 items reflecting 78 symptomatic cancer treatment-related symptoms.28,29  
Two PRO-CTCAE items address CIPN concerning the severity of the numbness and tingling 
and the degree that these symptoms have interfered with usual or daily activities. These items 
have previously been shown to have good psychometric properties.30 The two PRO-CTCAE 
items have the potential of providing a feasible patient-reported measure in a clinic setting.  
Nerve Conduction Studies (NCS): NCS measures impairment of electrical function in large 
peripheral nerves. NCS measures amplitude and latency of neuronal signaling. Reduction in 
the conduction velocity within a peripheral nerve indicates damage to the myelin, while 
reduction in the amplitude indicates axonal damage. Typical NCS findings suggestive of TIPN 
include slowed conduction velocity at common sites of entrapment (such as the carpal tunnel) 
and an earlier reduction of sural sensory amplitude relative to the radial nerve.31 A prospective 
study of patients receiving paclitaxel and carboplatin found a reduction in sural nerve 
conduction from baseline in terms of the sensory action potential amplitude (14.5 +/- 9.0 uV to 
9.7 +/- 7.1) and the sensory conduction velocity (54.6 +/- 7.7 m/s to 46.3 +/- 8.8).32 A series of 
patients who received paclitaxel and cisplatin had a reduction in the sural nerve amplitude of 
sensory action potential from average 13.7 uV (standard deviation 6.5) to 6.5 (standard 
deviation 4.1).33 NCS can be mildly painful for the patient; requires expertise and time to 
administer, and can only detect CIPN once it has progressed to the point that there is 
functional impairment of large peripheral nerves.34 Other functional assays besides NCS have 
been investigated. Sudomotor testing is a novel technique that uses the topical administration 
peripheral nerves. Although non-invasive, sudomotor testing tends to have wide variability 
which can make interpretation difficult and it has not yet been tested in chemotherapy-induced 
peripheral neuropathy.  A nerve excitability study is a novel non-invasive functional assay that 
detects the threshold of current that is needed to elicit an action potential. Similar to US, this 
experimental technique has been shown that it can detect oxaliplatin-induced peripheral 
neuropath.35  
Skin Biopsy and Intraepidermal Nerve Fiber Density (IENF): skin biopsies are able to detect 
CIPN with good diagnostic sensitivity that may be superior to NCS in chronic CIPN.36 
Measurement of the IENF density is a standard clinical assessment used in the evaluation of 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 5 of 55 
 
sensory predominant peripheral neuropathies. Healthy control participants have an average 
IENF density of 21.1 (standard deviation 10.4) at the thigh and 13.8 (standard deviation 6.7) in 
the distal leg.37,38 Typical IENF density findings in CIPN include reduced nerve fiber density 
that is typically more pronounced distally at the lower leg (mean 3.0, range 0.5-6.3) as 
compared to the thigh (mean 5.5, range 0.7-13.2).39 As expected, the IENF density likely 
continues to decrease with continued exposure to chemotherapy and worsening neuropathy, 
as a small longitudinal study of patients receiving oxaliplatin found that the distal leg IENF 
density progressively decreased from baseline 15.39 (6.75) to 12.89 (4.73) at 6 months to 9.45 
(3.92) at 12 months.40 However, IENF density has not been shown to be predictive of 
chemotherapy-induced peripheral neuropathy. 
Peripheral Nerve Ultrasound (US): US is a non-invasive, non-irradiating, emerging imaging 
modality which can be used to assess peripheral nerves. Nerve fiber cross-sectional area 
(CSA), echogenicity, and vascularity are assessed and provide an indication of nerve health 
and potential pathology. The majority of US data have been published on detection of 
entrapment syndromes such as carpal tunnel syndrome. In these cases the most common US 
findings include nerve enlargement, decreased echogenicity proximal to the entrapment, and 
an increase in nerve vascularity.41 Other studies have found that US can detect other 
peripheral nerve lesions or neuropathies, with the most reliable finding a change in nerve CSA. 
Ultrasound measurements of the sensory sural nerve at the distal calf in healthy participants 
without neuropathy had an average CSA of 5.3 mm2 with standard deviation 1.8 mm2 for a 
normal reference range of 1.7-8.9 mm2.42 Another ultrasound study assessed the sural nerve 
more distally at the ankle and found a smaller CSA which was significantly enlarged (p <0.001) 
in patients with diabetic polyneuropathy as compared to healthy controls (mean/standard 
deviation 2.59 / 0.96 mm2 as compared to 1.40 / 0.59 mm2).43  
Each of these assessments including patient-reported outcomes, physical examination, NCS, 
skin biopsy for IENF, and peripheral nerve ultrasound are standard of care for patients with 
sensory-predominant neuropathies such as CIPN and will be included in this trial to provide an 
objective assessment of peripheral nerve function. As standard of care tests, the risks of these 
studies are not different than those that would be encountered in routine clinical care for a 
patient undergoing comprehensive eletrophysiological evaluation of peripheral nerve 
pathology. Since the skin biopsy is an exploratory aim, patients will be allowed to participate in 
the study even if they are unwilling to have this measure. 
2.0 
Objectives 
 
The goal of this study is to obtain preliminary evidence of the effect of 8 acupuncture 
treatments over 10 weeks in breast and GI cancer patients who are currently receiving or 
recently completed active neurotoxic chemotherapy and have clinically documented grade 1 or 
2 neuropathy.  Specific objectives for this population and intervention are defined below. 
2.1 Primary Objective 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 6 of 55 
 
2.1.1 To obtain preliminary evidence of the clinical effects of acupuncture compared to usual 
care on the change in sensory neuropathic pain as measured by the EORTC QLQ-
CIPN20 sensory subscale. 
2.2. 
Secondary Objectives 
 
 
To obtain preliminary evidence of the clinical effects of acupuncture compared to usual care 
 
in: 
2.2.1 Change in the motor and autonomic neuropathic pain subscores on the EORTC QLQ-
CIPN20. 
 
2.2.2 Change in patient-reported assessment of numbness and tingling using the 2-item 
PRO-CTCAE measure. 
 
2.2.3 Preventing the escalation of CIPN from grade 1 or 2 to a higher grade. 
 
2.2.4 Amount and intensity of planned chemotherapy relative to completed chemotherapy if 
more chemotherapy is given or planned. 
 
2.2.5 Effect on sensory and motor nerve function via NCS (e.g. conduction velocity, latency, 
and amplitude). 
 
2.2.6 Effect on peripheral nerve swelling via nerve ultrasound (e.g. cross sectional area, CSA)  
2.3. 
Exploratory Objectives 
2.3.1 To obtain preliminary evidence on phenotypic differences between African-American 
and non A-A (i.e., white, Asian, etc.) with regard to presentation of CIPN as well as 
response to the intervention.  
 
2.3.2 To obtain preliminary evidence of the effect of acupuncture on intraepidermal nerve 
fiber density (IENF) via skin biopsy. 
 
2.3.3 To examine the associations among the peripheral nerve assessment measures (nerve 
conduction, peripheral nerve ultrasound, skin biopsy) and of the peripheral nerve 
assessment measures with the patient reported outcomes (EORTC QLQ-CIN20, PRO-
CTCAE) at baseline, week 12, and for the change from baseline to week 12. 
 
2.3.4 To examine the association between expectations of the effectiveness of acupuncture 
to reduce peripheral neuropathy and baseline, 12 week, and change in patient-reported 
outcomes on the EORTC QLQ-CIPN20 and PRO-CTCAE. 
 
3.0 
Study Population 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 7 of 55 
 
This study is designed to enroll breast and GI cancer patients who are currently receiving or 
recently completed active neurotoxic chemotherapy and have clinically documented grade 1 or 
2 neuropathy by CTCAE v5.0 criteria. 
3.1 
Inclusion Criteria 
 
o Breast or GI cancer stage I-III 
 
o Currently receiving or recently completed neurotoxic chemotherapy (either adjuvant or 
neoadjuvant). Currently is defined as including up until when the next cycle would be 
delivered, that is if the patient is getting chemotherapy every week, this would include a 
week after their last treatment; if the patient is getting treatment every 2 weeks, this 
would include 2 weeks after their last treatment; if the patient is getting treatment every 
3 weeks, this would include 3 weeks after their last treatment, etc. Recently completed 
is defined as 6 weeks after this time period. For example, if a patient was getting 
chemotherapy every week, this would include seven weeks after their last treatment; if 
the patient was getting treatment every 2 weeks, this would include 8 weeks after their 
last treatment; if the patient were getting treatment every 3 weeks, this would include 9 
weeks after their last treatment, etc.  
 
o Clinical symptoms of peripheral neuropathy of grade 1 or grade 2 as measured by the 
NCI-CTCAE.  
 
o Ability and willingness to understand and sign an informed consent. 
 
 
3.2 
Exclusion Criteria 
 
o Self-reported or documented history of UNRESOLVED pre-existing peripheral 
neuropathy due to diabetes, HIV, or other conditions.  
 
o Unable to provide medical history. 
 
o Male patients. 
 
o Pregnant 
 
o Unwilling to receive acupuncture or unable to travel for treatments. 
 
3.3 
Inclusion of women and minorities 
 
3.3.1 Patients of all races and ethnicity who meet the above-described eligibility criteria 
are eligible for this trial. 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 8 of 55 
 
3.3.2 We aim to enroll at least 25% Black or African Americans (N=6). Because of the 
low incidence of cancer among American Indian/Alaska Native, Asian, and 
Hispanic/Latinos in our catchment area, we do not expect accruals of individuals 
of those ancestries; however, no ancestry background is being excluded. Should 
we not meet or exceed these estimates, the PI will engage the Cancer Center 
Health Equity Advisory Group to discuss strategies to enhance recruitment in the 
target populations.   
4.0 
Methods 
4.1 
Registration Procedures 
All patients entered on any WFBCCC trial, whether treatment, companion, or cancer 
control trial, must be linked to a study protocol in EPIC within 24 hours of Informed 
Consent. Patients must be registered prior to the initiation of treatment. 
 
You must perform the following steps in order to ensure prompt registration of your 
patient: 
 
1. Complete the Eligibility Checklist (Appendix A) 
2. Complete the Protocol Registration Form (Appendix B) 
3. Complete the Ethnicity Verification Form (Appendix C) 
4. Alert the Cancer Center registrar by phone, and then send the signed Informed 
Consent Form, Eligibility Checklist and Protocol Registration Form to the registrar, 
either by fax or e-mail. 
 
*Protocol Registration is open from 8:30 AM - 4:00 PM, Monday-Friday. 
 
5. Fax/e-mail ALL eligibility source documents with registration. Patients will not be 
registered without all required supporting documents. 
To complete the registration process, the Registrar will: 
 
 assign a patient study number 
 register the patient on the study 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 9 of 55 
 
  
 
4.2  Study Activities 
 
                          Study Calendar* 
 
Screening 
Baseline 
Peripheral 
Nerve 
Assessment 
30 Day 
Follow-up (+ 
or – 5 days) 
Intervention 
(weeks  
2-12) 
Week 12 
End of 
Treatment 
Assessment 
 (10 +/2 
weeks post 
baseline) 
 
 
 
 
Post  
Treatment 
review 
Informed Consent 
X 
 
 
Randomizationh 
 
X 
 
 
 
 
Pregnancy Test for Women 
of Childbearing Potential 
X 
 
 
 
 
 
Medical history  
(Appendix D) 
X 
 
 
 
 
 
Physician Rated CTCAE 
(Appendix M)  
 
X 
 
 
X 
 
QLQ-CIPN20 (Appendix E) 
 
X 
 
 
X 
 
PRO-CTAE (Appendix E) 
 
X 
 
 
X 
 
Abbreviated Neurological 
Examination  
 
X 
 
 
X 
 
Nerve Conduction Studya 
(Appendix F) 
X 
 
X 
 
Peripheral Nerve 
Ultrasoundb 
(Appendix G) 
X 
 
X 
 
Skin Biopsyc (Appendix H) 
X 
 
X 
 
Acupuncture Expectancy 
Scale (Appendix P) 
 
X 
 
 
 
 
Follow-up Form for Skin 
Biopsy (Appendix J)g   
 
 
X 
 
 
 
X 
Research Blood Drawd 
 
X 
 
 
X 
 
Acupuncture treatments 
(Appendix O)e 
 
 
 
X 
 
 
Post treatment reviewf 
 
 
X 
 
 
X 
Adverse Events 
 
X 
X 
X 
X 
X 
Chemotherapy Form 
(Appendix N) 
 
 
 
 
 
 
X 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 10 of 55 
 
* The Study Calendar represents an ideal schedule for the completion of study related activities; however, depending on patient and 
physician availability, the completion of these clinical tasks may occur at any clinical encounter. ***The exceptions to this rule are 
following: the informed consent should be signed before any research activity occurs. While all study related tasks may be completed at 
a single visit, it is anticipated that due to scheduling, at least 2 study visits will be required. 
a. Sural,Tibial, and Median nerve assessments 
b. Sural, Tibial, and Median nerve assessments 
c. One skin biopsy will be obtained as 4-5mm punch at distal end of leg in sural nerve territory (10cm above lateral malleolus). 
d. Green top sodium heparin tube: 8 mL blood sample. 
e. Patients assigned to acupuncture will receive 8 treatments over a 10-week period. Appendix O is not required for participants who 
are randomized to the usual care group.  
f.  Patients will receive a post biopsy call 30 days after treatment to ensure safety and review adverse events.  
g. Appendix J is not required for participants who do not receive a skin biopsy (occurring 30 days after baseline and 30 days after 
follow-up). 
h Randomization is to be done after baseline visit. 
4.3 
Study setting 
Enrollment of participants will be take place at WFBMC Comprehensive Cancer Center 
(CCC) outpatient clinics. 
4.4 
Enrollment and Screening 
Patients being treated at WFBMC who are identified as having grade 1 or 2 neuropathy 
will be brought to the attention of the study nurse. Treating clinicians will introduce the 
study and consent will be obtained by either the clinical or research team.   
Non-WFBMC patients who respond to posted flyers will be directed to call a project 
specific phone line. The eligibility of non-WFBMC patients will be initially assessed via a 
brief telephone screen (Appendix Q) conducted by the Study in which study 
components and eligibility criteria are reviewed. If the patient is eligible and expresses 
interest in participating, a subsequent in-person appointment at Clinical Research Unit 
(CRU) Services facility will be scheduled with a study investigator who will review the 
patient’s EHR and conduct a physical exam of the patient’s nerve sensations. If the 
patient is still eligible and expresses interest in participating, consent will be obtained 
and a study visit will be scheduled at WFBMC to complete the clinical assessments 
outlined below.  
Clinical assessment will take place in the CCC outpatient clinic and will include a 
focused history by one of the study investigators or research employees. The medical 
record will also be reviewed to confirm details of the medical history. The focused 
history will assess age, body-mass index (BMI),  cancer staging, types and dosages of 
chemotherapy received, corticosteroid and analgesic use, and presence of 
comorbidities (diabetes, B12 deficiency, thyroid disorders, alcoholism, depression, 
carpal tunnel syndrome, sciatica).  A physical examination will occur and will also 
assess peripheral pulses and peripheral sensation. Clinical symptoms of peripheral 
neuropathy of grade 1 or grade 2 as measured by the NCI-CTCAE will be verified. The 
QLQ-CIPN20 questionnaire and Pro-CTCAE will also be administered at this encounter. 
Participants will be scheduled for the NCS, ultrasound, and skin biopsy (approximately 
2-2.5 hours) . Patients will receive a $25.00 gift card upon completion of the baseline 
peripheral nerve assessment and a $75 gift card upon completion of the follow-up 
assessment. Patients that live 60 miles or more from WFBMC will receive an additional 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 11 of 55 
 
$50 gift card upon completion of the baseline peripheral nerve assessment and an 
additional $50 gift card upon completion of the follow-up assessment. 
4.5 
Peripheral Nerve Assessment 
Peripheral nerve evaluation will be performed in the Diagnostic Neurology clinic at the 
WFBMC. Patients will undergo abbreviated neurological exam to assess strength of the 
tibialis anterior and gastrocnemius and deep tendon reflex exam of the Achilles tendon. 
Nerve conduction studies, nerve ultrasound and skin biopsies will be performed per 
standard of care on the affected lower limb and completed at a single visit. As standard 
of care tests, these tests results will be reported in the medical record for review by the 
patient’s treating oncologist. Skin biopsy tissue that remains after clinical assessment of 
IENF will be sent to Dr. Shiozawa’s lab for storage and exploratory assessment (see 
Section 4.5.4). 
4.5.1 Nerve Conduction Study 
CS technique and reference values for the sural and tibial nerves among healthy adults 
are based on data from Chen et al.44 and standard institutional practice.44 NCS 
assessment of the sural sensory nerve involves electrode placement at the ankle 
(posteroinferior to the lateral malleolus) and more distally with a 3cm bar for a distance 
of approximately 14cm; the nerve is stimulated at the calf midline with a display 
sensitivity 2-5 uV/div and sweep of 1 ms/div. The sural sensory nerve reference values 
for amplitude is a lower limit (3rd percentile) of 4 uV (onset-to-peak) and 4 uV (peak-to-
peak); and for latency is an upper limit (97th percentile) of 3.6 ms (onset) and 4.5 ms 
(peak). NCS assessment of the tibial motor nerve involves electrode placement at the 
medial foot (slightly anterior/inferior to the navicular tubercle) and more distally at the 
first metatarsophalangeal (MTP) joint for a distance of approximately 8cm; the nerve is 
stimulated at the ankle (posterior to the medial malleolus) and knee (at the midpopliteal 
fossa) with a display sensitivity 5 mV/div and sweep of 5 ms/div. The tibial motor nerve 
reference values for distal amplitude is a lower limit (3rd percentile) of 4.4 mV across all 
ages; and for distal latency is an upper limit (97th percentile) of 6.1 ms. 
4.5.2 Skin Biopsy 
One skin biopsy will be obtained as 4-5mm punch biopsy at distal end of leg in sural 
nerve territory (10cm above lateral malleolus). As described in a review by Lauria and 
Devigili45, biopsied tissue will be cut into 50 uM sections which will be hematoxylin and 
eosin stained and also immunostained with an antibody to PGP (protein gene product) 
9.5, a neuron- and neuroendocrine cell-specific ubiquitin carboxy-termiForm Onal 
hydrolase expressed throughout the peripheral nervous system. Slides will be reviewed 
by Dermatopathology (Dr. Sangueza) in order to count PGP9.5-positive fibers as they 
cross the dermal-epidermal junction to calculate linear density of IENF (IENF/mm). 
Additional staining will be done as indicated. Routine processing of specimens and 
comparison to standardized values (similar to those described by McArthur et al.37 will 
be done by Dermatopathology as per their institutional guidelines. These methods are 
standard clinical procedures for the routine assessment of IENF density. 
Dermatopathology will also obtain descriptive measures of morphologic changes that 
will be analyzed as an exploratory outcome. Additional unstained slides or blocks will be 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 12 of 55 
 
stored. Patients who are eligible to participate in the study, but unwilling to have a skin 
biopsy will be allowed to participate. 
4.5.3 Nerve Ultrasound 
Peripheral nerve US technique and reference values for the sural sensory (measured at 
the ankle) and tibial motor nerves are based on institutional data and standard 
institutional practice. These reference values were de-identified historical data which 
have also been published by Cartwright et al.42 as noted in the Introduction and 
Background section. Peripheral nerves will be assessed at non-compressive sites with a 
routine 15Hz linear probe. If available, a higher resolution 70Hz linear probe may be 
used – this would allow for descriptive characterization of nerve changes and would not 
be anticipated to cause variability in terms of CSA measurement as compared to the 
standard 15Hz US. 
 
4.5.4 Storage of Serum and Skin Biopsy Material 
Venous blood will be sampled at the time of peripheral nerve assessment (e.g. pre-
treatment and end-of-treatment) to explore potential circulating markers of peripheral 
nerve health.  
 
If the patient will undergo regularly scheduled phlebotomy on the day of peripheral 
nerve assessment, this blood draw will be preferentially added to the routinely collected 
specimens. Some participants may require an additional blood draw if insufficient blood 
samples were collected or regularly scheduled blood draw is not planned on the date of 
peripheral nerve assessment. For the purposes of this study, 16 mL of venous blood 
(8mL at each of two draws) will be collected in (2) 4mL (green-top) collection tubes and 
then transferred directly to Dr. Shiozawa’s lab for processing. Serum will be stored in 
Dr. Shiozawa’s lab. 
 
 
Blood Sample Preparation 
 
1. Email notification will be sent to Matt Eber (meber@wakehealth.edu), Sun Park 
(shpark@wakehealth.edu) and Yusuke Shiozawa (yshiozaw@wakehealth.edu) the day 
before the blood collection. 
 
2. Blood will be collected in a green-top vacutainer tube containing heparin (60 USP Units of 
Lithium Heparin/4 mL tube), and immediately inverted 8-10 times to prevent coagulation. 
Attention: Protocol #: CCCWFU # (97118) and the OnCore PID in addition to the other 
standard information should be on the tube. 
 
3. Samples will then be transported from the Cancer Center to the Shiozawa lab (Lab: 3-6624, 
3-5119, Office: 6-8743). 
4.6 
Randomization 
Following completion of the baseline visit, participants will be randomized to receive 
acupuncture immediately (acupuncture group) or to a usual care control group using a 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 13 of 55 
 
randomized block design developed by Dr. Tooze.  The randomization will be stratified 
by cancer type and race (AA, non-AA) to ensure balance within each race strata.  Block 
sizes will be chosen randomly to ensure that future assignments cannot be inferred from 
previous ones. 
4.7 
Intervention: Acupuncture Treatments  
Participants randomized to the acupuncture group will be scheduled to receive 8 
acupuncture treatments over a 10-week period.  All treatments will be conducted by a 
licensed acupuncturist at the Wake Forest Baptist Health Integrative Medicine Clinic 
Center. The first acupuncture treatment will be scheduled by the Study Coordinator.  
Future appointments will be scheduled by the participant and the Center.   
Up to 20 acupuncture points (bodily locations where acupuncture needles are inserted) 
will be selected for needling. We will use a standardized treatment plan rather than a 
personalized treatment plan given that the etiology of the symptoms is presumably the 
chemotherapy and that a procedure-based approach is more appropriate for CIPN than 
a diagnostic approach. In the case that a patient has a comorbidity effecting a specific 
area of the body, study investigators may allow for a deviation to the standardized 
acupuncture treatment plan as appropriate.    
Week 12 End of Treatment Assessment 
All patients will be scheduled for a follow-up assessment to occur 10 (+2) weeks after 
baseline (referred to as Week 12 assessment), regardless of whether they have 
completed all acupuncture treatments. The same protocol will be performed as 
described in Section 4.5 with addition of the QLQ-CIPN20 and PRO-CTCAE as 
described in Section 4.4. Peripheral neuropathy grade, as measured by the NCI-
CTCAE, will be assessed at this time by a clinician who is blinded as to the patient’s 
group (acupuncture vs. usual care) assignment. Participants who complete this 
assessment will receive a $75 gift card. If the patient lives 60 miles or more from 
WFBMC will receive an additional $50 gift card upon completion of the follow-up 
assessment. 
4.8 
Acupuncture for Usual Care Control Group 
Following completion of all measures, patients in the usual care group will be scheduled 
for their acupuncture visits. They will be instructed to contact the Wake Forest Baptist 
Health Integrative Medicine Clinic Center and provided up to 4 acupuncture treatments. 
These treatments are being provided as an incentive for patients to remain in the study 
to receive the end of treatment assessment.       
5.0 
Adverse Events List and Reporting Requirements 
5.1 
Adverse Event List for Acupuncture 
5.1.1 Acupuncture may sometimes cause temporary discomfort or pain, bleeding, 
bruising, or soreness.  
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 14 of 55 
 
5.1.2 There have been very rare reports of acupuncture causing minor nerve damage, 
hematomas (bleeding under the skin or inside your body), infections, or 
pneumothorax (puncture of a lung).  
5.2 
Adverse Event List for Nerve Conduction Studies 
5.2.1 Standard risks include discomfort or pain from the procedure.  
 
5.3 
Adverse Event List for Biopsies 
5.3.1 Risks associated with skin biopsies may include brief pain (common), bleeding or 
bruising (uncommon), or in rare instances, infection (rare). Standard precautions 
will be used for these tests. The risks are not expected to be different from 
routine clinical procedures. We do not expect any long-term, or life-threatening 
risks. 
5.4 
Adverse Event List for Ultrasound 
5.4.1 Ultrasound is a safe procedure. Patients may experience a slight warming and 
coldness from the gel. 
 
5.5 
Adverse Event Characteristics 
 
 
CTCAE term (AE description) and grade:  The descriptions and grading scales found in 
the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will 
be utilized for AE reporting. All appropriate treatment areas should have access to a copy of 
the CTCAE version 4.0. A copy of the CTCAE version 4.0 can be downloaded from the 
CTEP web site (http://ctep.cancer.gov). 
 
 
‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ (see Section 7.1 above) for 
expedited reporting purposes only.   
 
 
Attribution of the AE: 
 
Definite – The AE is clearly related to the study treatment. 
Probable – The AE is likely related to the study treatment. 
Possible – The AE may be related to the study treatment. 
Unlikely – The AE is doubtfully related to the study treatment. 
Unrelated – The AE is clearly NOT related to the study treatment. 
 
5.6 
STRC SAE Reporting Requirements 
 
The Safety and Toxicity Reporting Committee (STRC) is responsible for reviewing SAEs for WFBCCC 
Institutional studies as outlined in.  
The Safety and Toxicity Reporting Committee (STRC) is responsible for reviewing SAEs for 
WFBCCC Institutional studies as outlined in Appendix K. All Adverse Events that occur 
during protocol intervention and are coded as either 1) unexpected grade 4, 2) 
unplanned inpatient hospitalization > 24 hours (regardless of grade), or grade 5 (death) 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 15 of 55 
 
must be reported to the STRC using the using the SAE console in WISER.  All WFBCCC 
Clinical Protocol and Data Management (CPDM) staff members assisting a Principal 
Investigator in investigating, documenting and reporting an SAE qualifying for STRC reporting 
are responsible for informing a clinical member of the STRC as well as the entire committee 
via the email notification procedure of the occurrence of an SAE.  
 
5.7 
WFUHS IRB AE Reporting Requirements 
 
Any unanticipated problems involving risks to subjects or others and adverse events shall be promptly 
reported to the IRB, according to institutional policy. Reporting to the IRB is required regardless of the 
funding source, study sponsor, or whether the event involves an investigational or marketed drug, 
biologic or device. Reportable events are not limited to physical injury, but include psychological, 
economic and social harm. Reportable events may arise as a result of drugs, biological agents, 
devices, procedures or other interventions, or as a result of questionnaires, surveys, observations or 
other interactions with research subjects. 
 
All members of the research team are responsible for the appropriate reporting to the IRB and other 
applicable parties of unanticipated problems involving risk to subjects or others. The Principal 
Investigator, however, is ultimately responsible for ensuring the prompt reporting of unanticipated 
problems involving risk to subjects or others to the IRB. The Principal Investigator is also responsible 
for ensuring that all reported unanticipated risks to subjects and others which they receive are reviewed 
to determine whether the report represents a change in the risks and/or benefits to study participants, 
and whether any changes in the informed consent, protocol or other study-related documents are 
required. 
 
Any unanticipated problems involving risks to subjects or others occurring at a site where the study has 
been approved by the WFUHS IRB (internal events) must be reported to the WFUHS IRB within 7 
calendar days of the investigator or other members of the study team becoming aware of the event. 
 
Any unanticipated problems involving risks to subjects or others occurring at another site conducting 
the same study that has been approved by the WFUHS IRB (external events) must be reported to the 
WFUHS IRB within 7 calendar days of the investigator or other members of the study team becoming 
aware of the event. 
 
Any event, incident, experience, or outcome that alters the risk versus potential benefit of the research 
and as a result warrants a substantive change in the research protocol or informed consent 
process/document in order to insure the safety, rights or welfare of research subjects. 
 
6.0 
Duration of Follow-up 
Following recruitment, patients will be scheduled for neurodiagnostic assessments with 2 
weeks.  Acupuncture treatments will occur over 10 weeks, after which, patients will return to 
neurology for follow-up assessment within 2 weeks.  Patients randomized to usual care will have 
the opportunity to receive four acupuncture treatments . All patient will receive a telephone foll-
up call 30 days (+ or – 5 days) after their follow-up neurodiagnositc assessments to identify 
whether any adverse events have occurred.  

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 16 of 55 
 
7.0 
Outcome Measures 
Listed below are the primary, secondary and exploratory outcomes. Given that this is a pilot 
study, other parameters associated with nerve conduction and ultrasound studies will be 
captured and may be used for exploratory analyses and will include, but will not be limited to 
latency for nerve conduction studies and for ultrasound, echogenicity, vascularity, fascicle 
concentration, other qualitative descriptions of nerve changes, and other skin biopsy markers 
(e.g. macrophage infiltration, mast cell concentration, tryptase, chymase and histamine, etc). 
7.1 
Primary Outcome 
 5.1.1 Change in the sensory neuropathic pain score as measured by the EORTC QLQ 
CIPN20. 
7.2 
Secondary Outcomes 
 
7.2.1 Motor and autonomic pain subscores on the EORTC QLQ-CIPN20. 
 
7.2.2 PRO-CTCAE measure of numbness and tingling. 
 
7.2.3 CIPN as measured by NCI-CTCAE 5.0. 
 
7.2.4 Dose and number of cycles of planned chemotherapy and completed 
chemotherapy. 
 
7.2.5 Cross sectional area (CSA) of peripheral nerves as determined by ultrasound 
(sural CSA and median CSA). 
 
7.2.6 Amplitude, distal latency, and conduction velocity of nerve response derived from 
NCS (sural, tibial, and median). 
 
7.2.7 Nerve fiber density in the skin (IENF/mm) 
7.3 
Covariates 
 
7.3.1 BMI 
 
7.3.2 Age 
 
7.3.3 Cancer staging 
 
7.3.4 Types/dosages of systemic therapy 
 
7.3.5 Race (white/non-white) 
 
7.3.6 Use of analgesics or treatments for neuropathy 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 17 of 55 
 
7.3.7 Cancer Type 
 
7.3.8 Sex 
 
7.3.9 Neurotoxic chemotherapy 
 
8.0 
Statistical Considerations 
8.1 
Sample Size and Power 
The primary goal of this study is to provide preliminary data for future studies including 
estimating the variance of the sensory neuropathic pain patient-reported measures. 
There is an asymptote for the gain in the precision to estimate the variance with 20 
degrees of freedom. With a sample size of 22, the probability is 0.80 (80% confidence) 
that the estimate of the SD will be no more than 14% of the true population SD below 
the true population SD. 
8.2 
Analysis of Primary Objective 
 
Because this is a pilot study, analyses will be primarily descriptive to estimate variances 
and effect sizes for future work. Therefore, we will estimate means and standard 
deviations by group for the EORTC QLQ-CIPN20 sensory subscale at baseline and 
week 12, the correlation between the two measures, and the within-person change from 
baseline to week 12. To estimate effect size, we will use an ANCOVA model at week 
12, which will include the group and the baseline value.  The estimated difference 
between the groups and the variance will inform sample size calculations for future 
studies.  The ANCOVA approach is the most efficient method comparing change of an 
outcome between two groups.  We will estimate means by cancer type, treatment 
received, gender, and overall. 
8.3 
Analysis of Secondary Objectives 
 
Because the primary goals of the secondary objectives are to provide preliminary data 
on the effect of the intervention on the secondary outcomes of interest, we will use the 
same general approach as outlined above for the continuous variables (Objective 2.2.1,  
EORTC QLQ-CIPN20 motor and autonomic neuropathic pain subscale; Objective 2.2.2, 
PRO-CTCAE Numbness and Tingling; Objective 2.2.4, Dose and number of cycles of 
chemotherapy; Objectives 2.2.4, 2.2.5, and 2.2.6, Peripheral Nerve Assessments), i.e., 
means and standard deviations will be computed at baseline and week 12 by group, 
and for the change in the measures, and we will also estimate the correlation between 
the measures at the two time points, and fit ANCOVA models for each outcome of 
interest.  Because the primary interest in the measure of the CTCAE measure of CIPN 
is in the time to change of this categorical outcome, it will be assessed using 
frequencies of grade by time point (baseline, week 12), as well as whether the grade of 
CIPN increased, decreased or remained stable from baseline to week 12. A Fisher’s 
Exact test will be used to compare the groups at each time point and for the change 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 18 of 55 
 
during the study period.  We will estimate means by cancer type, treatment received, 
gender, and overall. 
 
8.4 
Analyses of Exploratory Outcome 
To meet objective 2.3.1, all of the descriptive statistics for the primary and secondary 
objectives will be computed by race subgroup (A-A, non-A-A), and ANCOVA models will 
be run including baseline value, group, race, and the interaction with race. 
 
To meet objective 2.3.2 (to obtain preliminary evidence of the effect of acupuncture on 
intraepidermal nerve fiber density (IENF) via skin biopsy, means and standard 
deviations will be computed at baseline and week 12 by group and for the change in 
measures.  We will estimate the correlation between the measures at the two time 
points. 
 
Objective 2.3.3 will be analyzed through calculating Pearson correlations of the 
association of the peripheral nerve assessments with each other and with the patient 
reported outcomes at each visit; change in the measures over the study will also be 
correlated. 
 
Objective 2.3.4. will be analyzed by correlating the expectancy rating scale score with 
baseline, 12 week, and changes in the EORTC QLQ-CIPN20 and PRO-CTCAE overall 
and by arm.  We will also classify participants into expectancy categories, and compare 
baseline, 12 week, and changes in EORTC QLQ-CIPN20 and PRO-CTCAE overall and 
by arm using an ANOVA.  If expectancy is related to baseline scores, we may use a 
mixed effects model to examine the trajectory of change related to expectancy, 
including arm in the model. 
 
8.5 
Accrual Rate 
4 participants per month. 
8.6 
Length of Study 
12 months 
9.0 
Data Management 
 
Informed consent document 
EPIC 
Protocol Registration Form (Appendix B) 
EPIC 
Clinical Evaluation from History/Exam (Appendix D) 
WISER/OnCore 
EORTC QLQ-CIPN20 (neuropathy scale) (Appendix E) 
REDCap 
PRO-CTCAE Numbness and Tingling (Appendix E) 
REDCap 
Nerve Conduction Study Data Collection Form (Appendix F) 
WISER/OnCore 
Ultrasound Nerve Diameter Data Form (Appendix G) 
WISER/OnCore 
Nerve Fiber Density Data Collection Form (Appendix H) 
WISER/OnCore 
Adverse Events Log (Appendix I) 
WISER/OnCore 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 19 of 55 
 
Follow-up Form for Skin Biopsy (Appendix J) 
WISER/OnCore 
CTCAE Neuropathy Grading Form (Appendix M) 
WISER/OnCore 
Chemotherapy Form (Appendix N) 
WISER/OnCore 
Acupuncture Treatment Form (Appendix O) 
WISER/OnCore 
10.0 Confidentiality and Privacy 
 
Confidentiality will be protected by collecting only information needed to assess study outcomes, 
minimizing to the fullest extent possible the collection of any information that could directly identify 
subjects, and maintaining all study information in a secure manner. To help ensure subject privacy 
and confidentiality, only a unique study identifier will appear on the data collection form. Any collected 
patient identifying information corresponding to the unique study identifier will be maintained on a 
linkage file, store separately from the data. The linkage file will be kept secure, with access limited to 
designated study personnel. Following data collection subject identifying information will be destroyed 
consistent with data validation and study design, producing an anonymous analytical data set. Data 
access will be limited to study staff. Data and records will be kept locked and secured, with any 
computer data password protected. No reference to any individual participant will appear in reports, 
presentations, or publications that may arise from the study. 
11.0 Data Safety and Monitoring 
 
The principal investigator will be responsible for the overall monitoring of the data and safety of study 
participants. The principal investigator will be assisted by other members of the study staff. 
12.0 Reporting of Unanticipated Problems, Adverse Events or Deviations 
 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes 
will be promptly reported by the principal investigator or designated member of the research team to 
the IRB and sponsor or appropriate government agency if appropriate. 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 20 of 55 
 
References 
 
1.  Amato A, Russell J. Neuromuscular Disorders. New York: McGraw Hill Medical; 2008. 
2.  Rivera DR, Ganz PA, Weyrich MS, Bandos H, Melnikow J. Chemotherapy-associated peripheral 
neuropathy in patients with early-stage breast cancer: A systematic review. J Natl Cancer Inst. 
2018;110(2). doi:10.1093/jnci/djx140 
3.  Simon NB, Danso MA, Alberico TA, Basch E, Bennett AV. The prevalence and pattern of 
chemotherapy-induced peripheral neuropathy among women with breast cancer receiving care 
in a large community oncology practice. Qual Life Res. 2017;26(10):2763-2772. 
doi:10.1007/s11136-017-1635-0 
4.  Schneider BP, Lai D, Shen F, et al. Charcot-Marie-Tooth gene, SBF2, associated with taxane-
induced peripheral neuropathy in African Americans. Oncotarget. 2015;7(50):82244-82253. 
doi:10.18632/oncotarget.12545 
5.  Seretny M, Currie GL, Sena ES, et al. Incidence, prevalence, and predictors of chemotherapy-
induced peripheral neuropathy: A systematic review and meta-analysis. PAIN. 
2014;155(12):2461-2470. doi:10.1016/j.pain.2014.09.020 
6.  Bandos H, Melnikow J, Rivera DR, et al. Long-term peripheral neuropathy in breast cancer 
patients treated With adjuvant chemotherapy: NRG Oncology/NSABP B-30. J Natl Cancer Inst. 
2018;110(2). doi:10.1093/jnci/djx162 
7.  Winters-Stone KM, Horak F, Jacobs PG, et al. Falls, functioning, and disability among women 
with persistent symptoms of chemotherapy-induced peripheral neuropathy. J Clin Oncol. June 
2017:JCO.2016.71.3552. doi:10.1200/JCO.2016.71.3552 
8.  Sittl R, Lampert A, Huth T, et al. Anticancer drug oxaliplatin induces acute cooling-aggravated 
neuropathy via sodium channel subtype Na(V)1.6-resurgent and persistent current. Proc Natl 
Acad Sci U S A. 2012;109:6704-6709. doi:10.1073/pnas.1118058109 
9.  Park SB, Goldstein D, Krishnan AV, et al. Chemotherapy-induced peripheral neurotoxicity: A 
critical analysis. CA Cancer J Clin. 2013;63(6):419-437. doi:10.3322/caac.21204 
10.  Dorsey S, Janelsins M. Chemotherapy induced peripheral neuropathy: developing novel trials 
informed by translational science. In: Rockville, MD; 2017. https://www.cancer.gov/about-
nci/organization/ccct/steering-committees/ncorp/symptom-
management/2017CIPNCTPM_ExecSum.pdf. 
11.  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 Off J Am Soc Clin Oncol. 2014;32(18):1941-
1967. doi:10.1200/JCO.2013.54.0914 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 21 of 55 
 
12.  Dimitrova A, Murchison C, Oken B. Acupuncture for the treatment of peripheral neuropathy: A 
systematic review and meta-analysis. J Altern Complement Med. 2017;23(3):164-179. 
doi:10.1089/acm.2016.0155 
13.  Greenlee H, DuPont-Reyes MJ, Balneaves LG, et al. Clinical practice guidelines on the 
evidence-based use of integrative therapies during and after breast cancer treatment. CA 
Cancer J Clin. 2017;67(3):194-232. doi:10.3322/caac.21397 
14.  Bao T, Goloubeva O, Pelser C, et al. A pilot study of acupuncture in treating bortezomib-induced 
peripheral neuropathy in patients with multiple myeloma. Integr Cancer Ther. 2014;13(5):396-
404. doi:10.1177/1534735414534729 
15.  Schroeder S, Meyer-Hamme G, Epplée S. Acupuncture for chemotherapy-induced peripheral 
neuropathy (CIPN): a pilot study using neurography. Acupunct Med. 2012;30(1):4-7. 
doi:10.1136/acupmed-2011-010034 
16.  Zhang R, Lao L, Ren K, Berman BM. Mechanisms of acupuncture–electroacupuncture on 
persistent pain. Anesthesiology. 2014;120(2):482-503. doi:10.1097/ALN.0000000000000101 
17.  Peters CM, Jimenez-Andrade JM, Kuskowski MA, Ghilardi JR, Mantyh PW. An evolving cellular 
pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous 
administration of paclitaxel in the rat. Brain Res. 2007;1168:46-59. 
doi:10.1016/j.brainres.2007.06.066 
18.  Zhang H, Li Y, de Carvalho-Barbosa M, et al. Dorsal root ganglion infiltration by macrophages 
contributes to paclitaxel chemotherapy-induced peripheral neuropathy. J Pain. 2016;17(7):775-
786. doi:10.1016/j.jpain.2016.02.011 
19.  Apostolidis L, Schwarz D, Xia A, Weiler M, Heiland S, Schlemmer H-P. Morphological correlates 
of ozaliplatin induced peripheral neuropathy assessed by magnetic resonance neurography. J 
Clin Oncol. 2017;35(15_suppl):10092-10092. doi:10.1200/JCO.2017.35.15_suppl.10092 
20.  Briani C, Campagnolo M, Lucchetta M, et al. Ultrasound assessment of oxaliplatin-induced 
neuropathy and correlations with neurophysiologic findings. Eur J Neurol. 2013;20(1):188-192. 
doi:10.1111/j.1468-1331.2012.03852.x 
21.  Speck RM, Sammel MD, Farrar JT, et al. Impact of chemotherapy-induced peripheral 
neuropathy on treatment delivery in nonmetastatic breast cancer. J Oncol Pract. 2013;9(5):e234-
e240. doi:10.1200/JOP.2012.000863 
22.  Forsyth P a., Balmaceda C, Peterson K, Seidman AD, Brasher P, Deangelis LM. Prospective 
study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing. J 
Neurooncol. 1997;35(1):47-53. doi:10.1023/A:1005805907311 
23.  Hershman DL, Weimer LH, Wang A, et al. Association between patient reported outcomes and 
quantitative sensory tests for measuring long-term neurotoxicity in breast cancer survivors 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 22 of 55 
 
treated with adjuvant paclitaxel chemotherapy. Breast Cancer Res Treat. 2011;125(3):767-774. 
doi:10.1007/s10549-010-1278-0 
24.  Postma TJ, Aaronson NK, Heimans JJ, et al. The development of an EORTC quality of life 
questionnaire to assess chemotherapy-induced peripheral neuropathy: The QLQ-CIPN20. Eur J 
Cancer. 2005;41(8):1135-1139. doi:10.1016/j.ejca.2005.02.012 
25.  Lavoie Smith EM, Barton DL, Qin R, Steen PD, Aaronson NK, Loprinzi CL. Assessing patient-
reported peripheral neuropathy: the reliability and validity of the European Organization for 
Research and Treatment of Cancer QLQ-CIPN20 Questionnaire. Qual Life Res. 
2013;22(10):2787-2799. doi:10.1007/s11136-013-0379-8 
26.  Eckhoff L, Knoop As, Jensen Mb, Ewertz M. Persistence of docetaxel-induced neuropathy and 
impact on quality of life among breast cancer survivors. Eur J Cancer. 2015;51(3):292-300. 
doi:10.1016/j.ejca.2014.11.024 
27.  Mols F, van de Poll-Franse LV, Vreugdenhil G, et al. Reference data of the European 
Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20 Questionnaire in 
the general Dutch population. Eur J Cancer. 2016;69:28-38. doi:10.1016/j.ejca.2016.09.020 
28.  Dueck AC, Mendoza TR, Mitchell SA, et al. Validity and reliability of the US National Cancer 
Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse 
Events (PRO-CTCAE). JAMA Oncol. 2015;1(8):1051. doi:10.1001/jamaoncol.2015.2639 
29.  Basch E, Reeve BB, Mitchell SA, et al. Development of the National Cancer Institute’s Patient-
Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-
CTCAE). J Natl Cancer Inst. 2014;106(9):dju244-dju244. doi:10.1093/jnci/dju244 
30.  Knoerl R, Gray E, Stricker C, et al. Electronic versus paper-pencil methods for assessing 
chemotherapy-induced peripheral neuropathy. Support Care Cancer. 2017;25(11):3437-3446. 
doi:10.1007/s00520-017-3764-y 
31.  Chen X, Stubblefield MD, Custodio CM, Hudis CA, Seidman AD, DeAngelis LM. 
Electrophysiological features of taxane-induced polyneuropathy in patients with breast cancer. J 
Clin Neurophysiol Off Publ Am Electroencephalogr Soc. 2013;30(2):199-203. 
doi:10.1097/WNP.0b013e3182767d3b 
32.  Argyriou AA, Polychronopoulos P, Iconomou G, Koutras A, Kalofonos HP, Chroni E. Paclitaxel 
plus carboplatin–induced peripheral neuropathy: A prospective clinical and electrophysiological 
study in patients suffering from solid malignancies. J Neurol. 2005;252(12):1459-1464. 
doi:10.1007/s00415-005-0887-8 
33.  Argyriou AA, Polychronopoulos P, Koutras A, et al. Clinical and electrophysiological features of 
peripheral neuropathy induced by administration of cisplatin plus paclitaxel-based chemotherapy. 
Eur J Cancer Care (Engl). 2007;16(3):231-237. doi:10.1111/j.1365-2354.2006.00718.x 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 23 of 55 
 
34.  Cavaletti G, Bogliun G, Marzorati L, et al. Grading of chemotherapy-induced peripheral 
neurotoxicity using the Total Neuropathy Scale. Neurology. 2003;61(9):1297-1300. 
doi:10.1212/01.WNL.0000092015.03923.19 
35.  Park SB, Goldstein D, Lin CS-Y, Krishnan AV, Friedlander ML, Kiernan MC. Acute abnormalities 
of sensory nerve function associated with oxaliplatin-induced neurotoxicity. J Clin Oncol. 
2009;27(8):1243-1249. doi:10.1200/JCO.2008.19.3425 
36.  Osmani K, Vignes S, Aissi M, et al. Taxane-induced peripheral neuropathy has good long-term 
prognosis: a 1- to 13-year evaluation. J Neurol. 2012;259(9):1936-1943. doi:10.1007/s00415-
012-6442-5 
37.  McArthur JC, Stocks EA, Hauer P, Cornblath DR, Griffin JW. Epidermal nerve fiber density: 
Normative reference range and diagnostic efficiency. Arch Neurol. 1998;55(12):1513. 
doi:10.1001/archneur.55.12.1513 
38.  Han Y, Smith MT. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN). 
Front Pharmacol. 2013;4. doi:10.3389/fphar.2013.00156 
39.  Krøigård T, Schrøder HD, Qvortrup C, et al. Characterization and diagnostic evaluation of 
chronic polyneuropathies induced by oxaliplatin and docetaxel comparing skin biopsy to 
quantitative sensory testing and nerve conduction studies. Eur J Neurol. 2014;21(4):623-629. 
doi:10.1111/ene.12353 
40.  Burakgazi AZ, Messersmith W, Vaidya D, Hauer P, Hoke A, Polydefkis M. Longitudinal 
assessment of oxaliplatin-induced neuropathy. Neurology. 2011;77(10):980-986. 
doi:10.1212/WNL.0b013e31822cfc59 
41.  Walker FO, Cartwright MS, Wiesler ER, Caress J. Ultrasound of nerve and muscle. Clin 
Neurophysiol. 2004;115(3):495-507. doi:10.1016/j.clinph.2003.10.022 
42.  Cartwright MS, Passmore LV, Yoon J-S, Brown ME, Caress JB, Walker FO. Cross-sectional 
area reference values for nerve ultrasonography. Muscle Nerve. 2008;37(5):566-571. 
doi:10.1002/mus.21009 
43.  Arumugam T, Razali SNO, Vethakkan SR, Rozalli FI, Shahrizaila N. Relationship between 
ultrasonographic nerve morphology and severity of diabetic sensorimotor polyneuropathy. Eur J 
Neurol. 2016;23(2):354-360. doi:10.1111/ene.12836 
44.  Chen S, Andary M, Buschbacher R, et al. Electrodiagnostic reference values for upper and lower 
limb nerve conduction studies in adult populations. Muscle Nerve. 2016;54(3):371-377. 
doi:10.1002/mus.25203 
45.  Lauria G, Devigili G. Skin biopsy as a diagnostic tool in peripheral neuropathy. Nat Clin Pract 
Neurol. 2007;3(10):546-557. doi:10.1038/ncpneuro0630 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 24 of 55 
 
Appendix A: Subject Eligibility Checklist 
IRB Protocol No. 00049061  
CCCWFU Protocol No. 97118 
Study Title: Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Principal Investigators:  Nancy E. Avis, PhD 
 
Inclusion Criteria 
(as outlined in study protocol) 
Criteria 
is met 
Criteria is 
NOT met 
Source Used to Confirm * 
(Please document dates and lab results) 
Breast or GI cancer 
□ 
□ 
 
Cancer stage I-III 
□ 
□ 
 
Currently receiving or recently completed 
neurotoxic chemotherapy (either 
adjuvant or neoadjuvant). Currently is 
defined as including up until when the 
next cycle would be delivered, that is if 
the patient is getting chemotherapy 
every week, this would include a week 
after their last treatment; if the patient is 
getting treatment every 2 weeks, this 
would include 2 weeks after their last 
treatment; if the patient is getting 
treatment every 3 weeks, this would 
include 3 weeks after their last 
treatment, etc. Recently completed is 
defined as 6 weeks after this time period. 
For example, if a patient was getting 
chemotherapy every week, this would 
include seven weeks after their last 
treatment; if the patient was getting 
treatment every 2 weeks, this would 
include 8 weeks after their last 
treatment; if the patient were getting 
treatment every 3 weeks, this would 
include 9 weeks after their last 
treatment, etc 
□ 
□ 
 
Clinical symptoms of peripheral 
neuropathy of grade 1 or grade 2 as 
measured by the NCI-CTCAE.  
 
Grade: ______________________ 
 
□ 
□ 
 
Ability and willingness to understand and 
sign an informed consent 
□ 
□ 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 25 of 55 
 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 26 of 55 
 
Exclusion Criteria 
(as outlined in study protocol) 
Criteria 
NOT 
present 
Criteria is 
present 
Source Used to Confirm * 
(Please document dates and lab results) 
Self-reported or documented history of 
UNRESOLVED pre-existing peripheral 
neuropathy due to diabetes, HIV, or 
other conditions. 
□ 
□ 
 
Unable to provide history 
□ 
□ 
 
Male patients 
□ 
□ 
 
Pregnant 
□ 
□ 
 
Unwilling to receive acupuncture or 
unable to travel for treatments. 
□ 
□ 
 
 
This subject is      
 eligible /  ineligible     for participation in this study. 
 
OnCore Assigned PID: __ __ __ __ __ __ __ __ 
 
Signature of research professional confirming eligibility:_______________________ 
Date (mm/dd/yy): __ __/__ __/__ __ 
 
Signature of Treating Physician:  ____________________________Date (mm/dd/yy):  __ __/__ __/__ __ 
 
Signature of Principal Investigator**:  ________________________  Date (mm/dd/yy):  __ __/__ __/__ __ 
* Examples of source documents include clinic note, pathology report, laboratory results, etc. When listing the source, 
specifically state which document in the medical record was used to assess eligibility. Also include the date on the 
document. Example: “Pathology report, 01/01/14” or “Clinic note, 01/01/14” 
 
**Principal Investigator signature can be obtained following registration if needed 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 27 of 55 
 
Appendix B: Protocol Registration Form 
 
DEMOGRAPHICS 
Patient: Last Name: _____________________ First Name: ___________________________ 
MRN:          ___ ___ ___ ___ ___ ___ ___ ___ DOB (mm/dd/yy): ___ ___ / ___ ___ / ___ ___ 
ZIPCODE: ___ ___ ___ ___ ___ 
 
 
SEX: 
 Male      Female 
Ethnicity (choose one):  Hispanic 
Non-Hispanic 
Race (choose all that 
apply): 
 WHITE           BLACK            ASIAN 
 PACIFIC ISLANDER                 NATIVE AMERICAN 
Height:   ___ ___.___ inches 
Weight: ___ ___ ___.___lbs.(actual) 
Surface Area: ___ ___.___m2 
         BMI: ___ ___.___kg/m2 
Primary Diagnosis: ____________________________________________________________ 
Date of Diagnosis(mm/dd/yy): ___ ___ /___ ___/___ ___ 
 
Performance Status: ___     ECOG   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Registrar can be contact by calling 336-713-6767 between 8:30 AM and 4:00 PM, Monday – Friday. 
 
Completed Eligibility Checklist and Protocol Registration Form must be hand delivered, faxed or e-mailed to the registrar at 
336-7136772 or registra@wakehealth.edu. 
 
 
 
PROTOCOL INFORMATION 
Date of Registration(mm/dd/yy): 
___ ___ / ___ ___ / ___ ___ 
MD Name (last) : 
______________________ 
Date protocol treatment started(mm/dd/yy): 
___ ___ / ___ ___ / ___ ___ 
Informed written consent: 
(consent must be signed prior to registration) 
 YES  NO 
 
Date Consent Signed(mm/dd/yy): 
___ ___ / ___ ___ / ___ ___ 
 
PID # (to be assigned by OnCore): 
___ ___ ___ ___ ___ ___ ___ ___ 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 28 of 55 
 
Appendix C - Race & Ethnicity Verification Form 
 
Thank you so much for helping us to verify your race and ethnicity to ensure the quality of our 
information. As a brief reminder, the information you provide today will be kept confidential. 
 
1. Are you: 
Hispanic or Latina 
Not Hispanic or Latina 
 
2. What is your race? One or more categories may be selected. 
White or Caucasian 
Black or African American 
American Indian or Alaskan Native 
Asian 
Native Hawaiian or Other Pacific Islander 
Other, Please Specify: ___________________________ 
 
 
 
 
 
 
 
 
 
 
 
Internal use only: 
 
 
Name: ____________________ MRN#: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Was the self-reported race and ethnicity of the participant verified at the time of consent? 
Yes        No 
 
Was a discrepancy found?       Yes         No 
If yes, please provide what is currently indicated in the EMR: 
Ethnicity: ____________________  
Race: ____________________ 
Additional comments: __________________________________________________________________ 
_____________________________________________________________________________________ 
_____________________________________________________________________________________
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 29 of 55 
 
Appendix D: Clinical Evaluation from History/Exam 
 
OnCore PID: __ __ __ __ __ __ __ __  
Date Completed (mm/dd/yy): __ __ / __ __ / __ __ 
 
PI: Nancy E. Avis, PhD  
 
Study Number: CCCWFU 97118 
 
Instructions: To be filled out by medical staff. 
 
1. Oncologic history 
a. Stage:  
clinical 
pathologic 
T: 
 0 
 is 
 1 
 2 
 3 
 4 
X 
N: 
 0 
1 
 2 
 3 
X 
M: 
0 
1 
X 
b. Current neurotoxic chemotherapy (if recently completed neurotoxic chemotherapy, skip b 
and continue with c):  
Name 
Neurotoxic 
Dose 
Start Date 
of regimen 
(mm/dd/yy
) 
Current 
cycle 
number 
Current 
week of  P, 
C, NP 
Standard 
neurotoxic 
dose? 
(circle) 
AC-T 
Doxorubicin/ 
cyclophosphamide 
followed by weekly 
paclitaxel (12 wk) 
80 mg/m2 
 
 
 
Yes    No* 
TC 
Docetaxel and 
cyclophosphamide 
75 mg/m2 
 
 
 
Yes    No* 
TCH 
Docetaxel/carboplatin/ 
trastuzumab 
75 mg/m2 
 
 
 
Yes    No* 
TCHP 
Docetaxel/carboplatin/ 
trastuzumab +pertuzumab 
75 mg/m2 
 
 
 
Yes    No* 
TH 
Paclitaxel (12 weeks) + 
trastuzumab 
80 mg/m2 
 
 
 
Yes    No* 
mFFX6 
mFOLFOX6 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
mFFX4 
FOLFOX 4 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
FFXI 
FOLFOXIRI 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
FFIX 
FOLFIRINOX 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
mFFIX 
mFOLFORINOX 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
FLOT 
FLOT 
T-50 mg/m2 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
NG 
Nabpaclitaxel and 
Gemcitabibe 
NP- 125 
mg/m2 
 
 
 
Yes    No* 
CP 
Carboplatin and Paclitaxel 
(CROSS regimen) 
C- AUC2 
P- 50 mg/m2  
 
 
Yes    No* 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 30 of 55 
 
 Oth 
Other (specify): 
 
 
 
 
 
Yes    No* 
 
*If reduced, is CIPN reason for reduction?  
Yes    
No   
Other:__________________ 
 
c. Previous neurotoxic chemotherapy (if, currently receiving neurotoxic chemotherapy. Skip c 
and continue with d):  
Name 
Neurotoxic 
Dose 
Start Date 
of regimen 
(mm/dd/yy
) 
Current 
cycle 
number 
Current 
week of  P, 
C, NP 
Standard 
neurotoxic 
dose? 
(circle) 
AC-T 
Doxorubicin/ 
cyclophosphamide 
followed by weekly 
paclitaxel (12 wk) 
80 mg/m2 
 
 
 
Yes    No* 
TC 
Docetaxel and 
cyclophosphamide 
75 mg/m2 
 
 
 
Yes    No* 
TCH 
Docetaxel/carboplatin/ 
trastuzumab 
75 mg/m2 
 
 
 
Yes    No* 
TCHP 
Docetaxel/carboplatin/ 
trastuzumab +pertuzumab 
75 mg/m2 
 
 
 
Yes    No* 
TH 
Paclitaxel (12 weeks) + 
trastuzumab 
80 mg/m2 
 
 
 
Yes    No* 
mFFX6 
mFOLFOX6 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
mFFX4 
FOLFOX 4 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
FFXI 
FOLFOXIRI 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
FFIX 
FOLFIRINOX 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
mFFIX 
mFOLFORINOX 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
FLOT 
FLOT 
T-50 mg/m2 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
NG 
Nabpaclitaxel and 
Gemcitabibe 
NP- 125 
mg/m2 
 
 
 
Yes    No* 
CP 
Carboplatin and Paclitaxel 
(CROSS regimen) 
C- AUC2 
P- 50 mg/m2  
 
 
Yes    No* 
 Oth 
Other (specify): 
 
 
 
 
 
Yes    No* 
 
*If reduced, was CIPN reason for reduction?  
Yes    
No   
Other:__________________ 
 
 
d. Other current cancer therapy:  
 hormone  
 other: ________________________ 
 
e. Other prior cancer therapies (excluding 1c.) for most recent cancer. Mark all that 
apply: 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 31 of 55 
 
 Chemotherapy  
 Radiation  
 Surgery  
 Hormone therapy 
 Other: _____________ 
 None   
 
2. Date of onset of CIPN (mm/dd/yy): __ __/__ __/__ __ 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 32 of 55 
 
 
OnCore PID: __ __ __ __ __ __ __ __  
Date Completed (mm/dd/yy): __ __ / __ __ / __ __ 
 
PI: Nancy E. Avis, PhD  
 
Study Number: CCCWFU 97118 
 
3. Medical history (check all that apply, if unknown can be left unchecked): 
 Thyroid Disorder:  
If yes: 
 Hyperthyroidism 
   
Hypothyroidism   
Other; specify: _____   
_____  
 Vitamin B12 deficiency 
 Peripheral vascular disease (claudication, arterial bypass, untreated aneurysm ≥6cm) 
 Cerebrovascular disease (history of TIA or CVA) 
 Alcoholism 
 Carpal tunnel syndrome 
 Sciatica 
 Diabetes: If yes, end organ damage? Yes 
 
No 
 
 AIDS 
 Depression 
 Other major medical condition; specify______________________________ 
 
4.   List all prescription and over-the-counter medications (includes prescription supplements) 
Medication Name 
Is it PRN? 
Medication Name 
Is it PRN? 
1. 
yes          no 
11. 
yes          no 
2. 
yes          no 
12. 
yes          no 
3. 
yes          no 
13. 
yes          no 
4. 
yes          no 
14. 
yes          no 
5. 
yes          no 
15. 
yes          no 
6. 
yes          no 
16. 
yes          no 
7. 
yes          no 
17. 
yes          no 
8. 
yes          no 
18. 
yes          no 
9. 
yes          no 
19. 
yes          no 
10. 
yes          no 
20. 
yes          no 
 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 33 of 55 
 
5. List all supplements  
Supplement Name 
Taking? 
If yes - taken for neuropathy? If yes - PRN? 
Multivitamin 
yes          no 
yes          no 
yes          no 
B12 
yes          no 
yes          no 
yes          no 
B vitamin complex 
yes          no 
yes          no 
yes          no 
Vitamin C 
yes          no 
yes          no 
yes          no 
Vitamin E 
yes          no 
yes          no 
yes          no 
Vitamin D 
yes          no 
yes          no 
yes          no 
Calcium 
yes          no 
yes          no 
yes          no 
Iron 
yes          no 
yes          no 
yes          no 
Probiotics 
yes          no 
yes          no 
yes          no 
Fiber 
yes          no 
yes          no 
yes          no 
Tumeric 
yes          no 
yes          no 
yes          no 
Fish oil/omega-3/flaxseed 
yes          no 
yes          no 
yes          no 
Other:____________________ yes          no 
yes          no 
yes          no 
Other:____________________ yes          no 
yes          no 
yes          no 
Other:____________________ yes          no 
yes          no 
yes          no 
Other:____________________ yes          no 
yes          no 
yes          no 
Other:____________________ yes          no 
yes          no 
yes          no 
Other:____________________ yes          no 
yes          no 
yes          no 
 
 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 34 of 55 
 
Appendix E Patient Reported Outcomes: EORTC QLQ-CIPN20 and 
PRO-CTCAE 
 
OnCore PID: __ __ __ __ __ __ __ __ 
Date Completed (mm/dd/yy): __ __ / __ __ / __ __ 
PI:  Nancy E. Avis, PhD   Study Number: CCCWFU 97118 
 
Visit:  Baseline 
       
 
12 week  
 
EORTC QLQ-CIPN20 
 
Patients sometimes report that they have these 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. 
DURING THE PAST WEEK 
Not 
at 
all 
A 
little 
Quite 
a bit 
Very 
much 
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 in 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 in manipulating small objects 
with your fingers (for example, fastening small 
buttons)? 
1 
2 
3 
4 
13) Did you have difficulty in opening a jar or bottle 
because of weakness in your hands? 
1 
2 
3 
4 
14) Did you have difficulty walking because your feet 
dropped downwards? 
1 
2 
3 
4 
15) Did you have difficulty in climbing stairs or getting 
up out of a chair because of weakness in your legs? 
1 
2 
3 
4 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 35 of 55 
 
DURING THE PAST WEEK 
Not 
at 
all 
A 
little 
Quite 
a bit 
Very 
much 
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 in hearing? 
1 
2 
3 
4 
Please answer the following question only if you drive a 
car: 
19) Did you have difficulty using the pedals? 
Or mark:  Not applicable:  I do not drive a car 
1 
2 
3 
4 
 
PRO-CTCAE 
As individuals go through treatment for their cancer they sometimes experience different 
symptoms and side effects. For each question, please mark the one box that best describes 
your experiences over the past 7 days. 
 
PRO-CTCAE™ Symptom Term: Numbness & tingling 
a. In the last 7 days, what was the SEVERITY of your NUMBNESS OR TINGLING IN YOUR 
HANDS OR FEET at its WORST? 
o None 
o Mild 
o Moderate 
o Severe 
o Very 
Severe 
b. In the last 7 days, how much did NUMBNESS OR TINGLING IN YOUR HANDS OR FEET 
INTERFERE with your usual or daily activities? 
o Not at all 
o A little 
bit 
o Somewhat 
o Quite a 
bit 
o Very 
much 
 
The PRO-CTCAE™ items and information herein were developed by the Division of Cancer Control and Population 
Sciences in the NATIONAL CANCER INSTITUTE at the NATIONAL INSTITUTES OF HEALTH, in Bethesda, 
Maryland, U.S.A. Use of the PRO- CTCAE™ is subject to NCI’s Terms of Use 
 
1. Are you currently taking any medications or supplements (such as gabapentin/Neurontin, 
amitriptyline/Elavil, nortriptyline/Pamelor, vitamin B12, pain medications) for your neuropathy? 
       No 
       Yes   
1a.  What are you taking?  ____________________________ 
1b.  When did you start taking this?  ____________________ 
 
2. Are you currently doing anything else to treat your neuropathy (such as meditation, massage, 
yoga)? 
      No   
      Yes   
2a.  What are you doing? ______________________________ 
2b.  When did you start doing this?  ______________________ 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 36 of 55 
 
Appendix F: Nerve Conduction Study Data Collection Form 
 
OnCore PID: __ __ __ __ __ __ __ __  
Date Completed (mm/dd/yy): __ __ / __ __ / __ __ 
 
PI: Nancy E. Avis, PhD  
Study Number: CCCWFU 97118 
 
Visit:  Baseline   
  12 week 
 
Instructions 
 
Use the OnCore PID and visit to Identify the Sample 
 
Date is the date of experimentation and listed before the technique. Use the following 
format (mm/dd/yy) 
 
Do not erase entries. If an entry is incorrect, cross the entry out, initial, and write in the 
correct entry. Please write neatly. 
 
 
 
 
 
Nerve Conduction Worksheet 
 
Date of Nerve Conduction Study: __ __/__ __/__ __ 
 
Conduction studies 
Tibial 
Sural 
Median 
Done          Not Done 
Done          Not Done 
Done          Not Done 
 
Amplitude 
Latency 
Conduction 
Velocity 
Amplitude 
Latency 
Conduction 
Velocity 
 
Amplitude 
Latency 
Conduction 
Velocity 
Ankle 
 
 
 
 
 
 
Wrist 
 
 
 
Pop 
Fossa 
 
 
Elbow 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 37 of 55 
 
Appendix G: Ultrasound Nerve Diameter Data Form 
 
OnCore PID: __ __ __ __ __ __ __ __  
Date Completed (mm/dd/yy): __ __ / __ __ / __ __ 
 
PI: Nancy E. Avis, PhD 
 Study Number: CCCWFU 97118 
 
Visit: Baseline 
 
          12 week  
 
To be used for determination of tibial, sural and median nerve diameters. 
 
Date of Procedure (mm/dd/yy):  __ __/__ __/__ __ 
 
Nerve 
Probe Location 
and Landmark 
Side 
(circle) 
Area 
(mm2) 
Fascicles Vascularity Mobility 
Sural 
 
left    
right 
 
 
 
 
Superficial 
peroneal 
 
left    
right 
 
 
 
 
Median 
 
left    
right 
 
 
 
N  INC  DEC  A  NA 
Other: 
____________ 
 
 
 
 
 
 
 
 
 
 
 
Person recording information: ________________________________ 
 
 
 
 
 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 38 of 55 
 
Appendix H: Nerve Fiber Density Data Collection Form 
 
OnCore PID: __ __ __ __ __ __ __ __  
Date Completed (mm/dd/yy): __ __ / __ __ / __ __ 
 
PI: Nancy E. Avis, PhD 
 Study Number: CCCWFU 97118 
 
Visit:  Baseline  
          12 week  
 
Instructions 
 
Use the OnCore PID to Identify the Sample 
 
Date is the date of experimentation and listed before the technique. Use the following 
format(mm/dd/yy) 
 
Initials of person performing the assay. 
 
Do not erase entries. If an entry is incorrect, cross the entry out, initial, and write in the 
correct entry. Please write neatly. 
 
Date of Biopsy(mm/dd/yy): __ __/__ __/__ __ 
 
Nerve Fiber Density Form 
Location of Biopsy 
Side 
(circle) 
Nerve Fiber Density 
(IENF/mm) 
 Distal leg 
left   
right 
 
 Other: 
_____________________ 
 
 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 39 of 55 
 
Appendix I: Adverse Events Log 
 
WFBCCC Adverse Event (AE) Log 
PI: _________________    
Subject PID: ___ ___ ___ ___ ___ ___ ___ ___ 
MRN: ___ ___ ___ ___ ___ ___ ___ ___ 
Cycle #: ____   
Cycle Start Date(mm/dd/yyyy): ___ ___/___ ___/___ ___ 
___ ___ 
Cycle Start Time: ___ ___:___ __   
Cycle End Date(mm/dd/yyyy): ___ ___/___ ___/___ ___ 
___ ___  
Cycle End Time: ___ ___:___ ___  
Adverse 
Event 
CTC 
Term 
Lab 
Value 
Grade    
(1-5) 
per 
CTC 
Start 
Date 
Attribution 
DEF=Definite 
PROB=Probable 
POSS=Possible 
UNLK=Unlikely 
UNRL=Unrelated 
Treating MD 
Initials/Date 
End 
Date 
Expected 
N=No   
Y=Yes 
Serious Adverse 
Event Detail        
NO=No               
LT=Life Threatening 
DTH=Death 
DIS=Disability 
HOS=Hospitalization    
CA=Caused 
congenital anomaly     
RI=Required 
intervention to 
prevent impairment 
Dose 
Limiting 
Toxitity 
(DLT)      
N=No      
Y=Yes 
Action Taken 
NO=None          
DR=Dose 
Reduced 
RI=Regimen 
Interrupted          
TD=Therapy 
discontinued 
INTR=Interrupted 
then reduced 
Therapy Given   
NO=None  
SYM=Symptomatic  
SUP= Supportive    
VSUP=Vigorous 
supportive 
Reportable?    
IRB-IRB       
STRC-STRC    
FDA-FDA      
SPON-
Sponsor 
(Mark all that 
apply) 
Adverse 
Event 
Report 
(AER) 
Filed      
N=No   
Y=Yes 
Outcome  
R=Recovered 
TX=Still under 
treatment/ 
observation 
A=Alive with 
sequalae 
D=Died 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Serious Adverse Event: Hospitalization; Disability; Birth Defect; Life-threatening; Death. 
CTCAE Version 4 - http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf 
STRC- Safety and Toxicity Review Committee 
Version 10/30/17 
 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 40 of 55 
 
Appendix J: Follow-up Form for Skin Biopsy 
 
OnCore PID: __ __ __ __ __ __ __ __  
 
Date Completed(mm/dd/yy): __ __ / __ __ / 
__ __ 
 
PI: . Nancy E. Avis, PhD 
  Study Number: CCCWFU 97118 
 
Instructions: Use this form as follow-up after the skin biopsies to record any 
complications related to the skin biopsy.  If any problems are reported, 
complete the AE log. Appendix J is not required for participants who 
do not receive a skin biopsy (occurring 30 days after baseline and 
30 days after follow-up). 
 
Visit:  Baseline  
12 week  
 
 
* Reason assessment not completed within 30 days:____________________________ 
______________________________________________________________________ 
______________________________________________________________________ 
 
 
** Skin biopsy problems reported by participant:________________________________ 
______________________________________________________________________ 
______________________________________________________________________ 
 
** Date AE log completed: __ __/__ __/__ __ 
Date of Skin 
Biopsy 
(mm/dd/yy) 
Date of Phone /  
In-person 
assessment 
(mm/dd/yy) 
Phone / In-person 
assessment completed 
within 30 days? 
(circle one) 
 
Any skin biopsy problems 
reported by participant? 
(circle one) 
__ __/__ __/__ __ 
 
__ __/__ __/__ __ 
 
Yes   /     No* 
 
*If no, describe reason 
below 
 
 
Yes**     /     No 
 
**If yes, describe problems 
below and complete AE 
log 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 41 of 55 
 
Appendix K: Mandatory STRC SAE Reporting Requirements 
 
Safety and Toxicity Review Committee 
(STRC; previously known as CROC)  Serious 
Adverse Event (SAE) Notification SOP 
     Date: 7/10/2019 
 
 
Mandatory STRC SAE Reporting Requirements in WISER  
This document describes reporting requirements of adverse events 
from WFBCCC Investigator Initiated interventional trials to the Safety and Toxicity 
Review Committee (STRC). A trial is considered a WFBCCC Investigator Initiated 
interventional trial if the following criteria are met:  
  
1. 
The Principal Investigator (PI) of the trial is a member of a department at 
the Wake Forest University Baptist Medical Center.  
2. 
WFBCCC is considered as the primary contributor to the design, 
implementation and/or monitoring of the trial.  
3. 
The trial is designated as “Interventional” using the Clinical Research Categories 
definitions provided by the NCI in the Data Table 
4 documentation. (https://cancercenters.cancer.gov/GrantsFunding/DataGuide#dt4)  
  
There are two distinct types of WFBCCC Investigator Initiated interventional trials 
based on where patient enrollment occurs.  These include:  
  
1. 
Local WFBCCC Investigator Initiated interventional trials defined as trials 
where all patients are enrolled from one of the WFBCCC sites. These include the 
main outpatient Cancer Center clinics (located in Winston-Salem) as well as WFBCCC 
affiliate sites located in Bermuda Run (Davie Medical Center), Clemmons, Lexington, 
High Point, or Wilkesboro.  
2. 
Multi-Center WFBCCC Investigator Initiated interventional trials defined as 
trials where patients are enrolled from other sites in addition to WFBCCC sites.    
There are three types of trials that are included in this category:  
a. 
Trials sponsored by the NCI Community Oncology Research 
Program (NCORP) that are conducted at multiple sites where the PI is a member 
of a department at the Wake Forest University Baptist Medical Center.  
b. 
Trials sponsored by Industry that are conducted at multiple sites and the 
PI is a member of a department at the Wake Forest University Baptist 
Medical Center.  
c. 
Trials sponsored by WFBCCC that are conducted at multiple sites and the 
PI is a member of a department at the Wake Forest University Baptist 
Medical Center.  
  
All Adverse Events (AEs) and Serious Adverse Events (SAEs) that occur on any 
patients enrolled on WFBCCC Investigator Initiated Interventional trials must be entered 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 42 of 55 
 
into the WISER system. The only exception to this requirement is for patients enrolled on 
NCORP trials at non- WFBCCC sites. AEs and SAEs for NCORP patients enrolled at WFBCCC 
sites must be entered into the WISER system. Once these AEs and SAEs are entered in 
WISER, certain actions must be taken regarding the reporting of specific Adverse Events to 
the STRC.  
All Adverse Events that occur during protocol intervention (defined below) and are coded as 
either 1) unexpected grade 4, 2) unplanned inpatient hospitalization > 24 hours (regardless 
of grade), or grade 5 (death) must be reported to the STRC using the using the SAE console 
in WISER.  
  
A research nurse or clinical research coordinator when made aware that an 
adverse event meets one of the above criteria has occurred on a WFBCCC Investigator 
Initiated interventional trial, is responsible for informing a clinical member of the STRC by 
phone (or in-person) about the adverse event. The nurse/coordinator should contact the 
treating physician prior to calling the STRC clinical member to obtain all details of the SAE, as 
well as all associated toxicities to be recorded along with the SAE. In addition, this nurse or 
coordinator is responsible for entering the adverse event information into the SAE console in 
WISER.  Once the adverse event has been entered into the SAE console an email informing 
the entire STRC committee will be generated.  
  
THESE REPORTING REQUIREMENTS APPLY TO any staff member on the study team 
for a WFBCCC Institutional Interventional trial. Ultimately, the protocol PI has 
the primary responsibility for AE identification, documentation, grading and assignment of att
ribution to the investigational agent/intervention. However, when an AE event as described 
above is observed, it is the responsibility of the person who observed the event to be sure 
that it is reported to the STRC.  
  
What is considered during protocol intervention?  
During protocol intervention is considered to be the time period while a patient is 
on study treatment or during the time period within 30 days of last study treatment (even 
if patient begins a new (non-study) treatment during the 30 days). This window of 30 days 
should be the standard window to be used in all protocols unless a specific scientific 
rationale is presented to suggest that a shorter window can be used to identify events. If it is 
a trial sponsored by Industry and the sponsor requires a longer window for monitoring of 
SAEs, then the longer window of time specified by the sponsor should be followed.  
  
What is considered as an Unexpected Grade 4 event?  
Any grade 4 event that was not specifically listed as an expected adverse event in 
the protocol should be considered as unexpected. A grade 4 adverse event can be considered 
to be unexpected if it is an event that would not be expected based on the treatment 
being received or if it is unexpected based on the health of the patient. In either case, if there 
is any uncertainty about whether a grade 4 adverse event is expected or unexpected it 
should be reported to STRC.  

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 43 of 55 
 
  
STRC notification responsibilities of the person (e.g., nurse) handling the 
reporting/documenting of the SAE in WISER:  
1. Make a phone call (or speak in person) to the appropriate clinical member of the STRC 
as listed below (page if necessary)  
2. Enter a new SAE into the SAE module that is located in the Subject>> 
CRA Console in WISER WITHIN 24 HOURS of first knowledge of the event. Information can 
be entered and saved, but the STRC members will not be notified until 
a date is entered into the STRC Notification Date Field. This will ensure that all persons that 
need to be made aware of the event (i.e., study team members and STRC members) will 
be notified; remember to file a copy of the confirmation.  
3. Document that the appropriate person(s) on the STRC has been contacted. 
Indicate the name of the STRC clinician that was contacted in the Event Narrative field in 
the SAE console of the particular subject.  
4. Document whether or not the protocol should be suspended based on 
the discussion with the STRC clinician. This is the major function of the email notification. 
Enter whether the protocol should be suspended in the Event Narrative Field.  
5. Follow up/update the clinical member(s) of STRC regarding any new developments 
or information obtained during the course of the SAE investigation and reporting process.  
  
Elements needed to complete the SAE form in the Subject Console in WISER (see Screen 
Shot 3):  
1. Event Date  
2. Reported Date  
3. Reported by  
4. If Grade 5, enter Death Date  
5. If Grade 5, enter Death occurred: within 30 days  
6. Event Narrative: Brief description (include brief clinical history relevant to 
this event, including therapies believed related to event). Begin narrative with the 
STRC clinician who was notified and Date/Time notified. In addition, state attribution by 
STRC clinician as either “Unrelated”, “Unlikely”, “Possibly”, “Probably”, or 
“Definitely”.  Always include the following here:  
i. STRC clinician name and comments  
ii.Date of last dose before the event  
iii.Is suspension of the protocol needed? Y/N  
7. Treating Physician comments  
8. PI comments, if available  
9. Protocol Attribution after discussion with STRC clinician  
10. 
Outcome 
(Fatal/Died, 
Intervention 
for 
AE 
Continues, 
Migrated 
AE, 
Not Recovered/Not Resolved, Recovered/Resolved with Sequelae, Recovered/Resolved 
without Sequelae, Recovering and Resolving)  
11. 
Consent form Change Required? Y/N  

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 44 of 55 
 
12. 
SAE Classification *This is required in order for the email notification to be sent*  
13. 
Adverse Event Details – Enter all details for each AE associated with the SAE.  
a. Course start date  
b. Category  
c. AE Detail  
d. Comments  
e. Grade/Severity  
f. Unexpected Y/N  
g. DLT Y/N  
h. Attributions  
i. Action  
j. Therapy  
k. Click ADD to attach the AE Detail to the SAE.  
14. 
Enter Date Notified STRC -- *This is required for the email notification to 
be sent*  
15. 
Click Submit. The auto-generated notification email will disseminate within 5 
minutes. If you do not receive an email within 5 minutes, check that you have entered the 
“Date Notified STRC” and the “SAE Classification”. If these have been entered and the 
email still has not been received, take a screen shot of the SAE in WISER and immediately 
email it out to all of the STRC members listed in this SOP. In the subject line, indicate that 
this is a manual transmission of the SAE in lieu of the auto-generated email. It is required 
that a notification goes to the STRC members immediately so that their assessment can be 
obtained within the 24 hour time frame requirement. Contact the Cancer Center 
Programmer/Analyst to alert that there is an issue with the auto-generated email.  
  
The Clinical Members of STRC to Notify by Phone or Page:  
Bayard Powell, MD –  
Glenn Lesser, MD –Stefan Grant, MD, JD 
Jimmy Ruiz, MD- 
Mercedes Porosnicu, MD-  
         Michael Farris, MD – 
  
Definition of Unavailable:  
As a general guideline if the first clinician that is contacted does not respond to the 
phone call or page within 30 minutes, then initiate contact with a different STRC clinician. 
Allow up to 30 minutes for the new STRC clinician to respond to a phone call or page 
before contacting another member. These times (30 minutes) are a general guideline. Best 
judgment as a clinical research professional should be used giving considerations of the time 
of day, severity of the SAE, and other circumstances as to when it is appropriate to contact 
backup clinicians. If the event occurs near the end of day, then leave messages (voice or 
email) as appropriate and proceed with submitting the STRC notification form. It is important 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 45 of 55 
 
to take reasonable steps and to document that some type of contact has been initiated to 
one or more of the clinical members of STRC.  
  
STRC CLINICAN RESPONSIBILITY:  
It is the responsibility of the STRC clinician to review all reported events, evaluate the 
events as they are reported; and communicate a response to the Investigator, event reporter 
and the members of STRC. The review will include but not be limited to the information 
reported; there may be times when additional information is needed in order for an 
assessment to be made and further communication directly with the investigator may be 
warranted. STRC reserves the right to disagree with the Investigator's assessment. If STRC 
does not agree with the 
Investigator, STRC reserves the right to suspend the trial pending further investigation. If ther
e is any immediate danger or harm that could be present for a future patient based on 
the information provided in the STRC report then an immediate suspension of enrollment 
should be considered.  
  
AMENDMENTS TO PREVIOUS REPORTS  
If all pertinent information is unavailable with the initial submission, once the 
additional information is available do not submit a new report. Rather, go to the original 
email that was sent to the STRC and using that email “reply to all”. Entitle this new email 
“Amendment for (list date of event and patient ID)” this will avoid duplications of the same 
event. List the additional information being reported. This information needs to be entered 
into WISER as well. To do this, go to the Subject console and click SAEs on the left column. 
Click on the 
appropriate SAE number that needs updating. Then click update. This will allow additional in
formation to be added  
  
  
   
Acronyms  
AE – Adverse Event  
STRC-Safety and Toxicity Review Committee  
SAE-Serious Adverse Event  
WFBCCC – Wake Forest Baptist Comprehensive Cancer Center  
NCI-National Cancer Institute  
WISER –Wake Integrated Solution for Enterprise Research  
Screen Shots:  
  
The following screen shots come from the SAE Console within the Subject Console in WISER.  
 
 
 Screen Shot 1: 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 46 of 55 
 
 
  
Screen Shot 2:
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 47 of 55 
 
 
Screen Shot 3:  
  
  
 
Screen Shot 4:  
 
  
 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 48 of 55 
 
 
Appendix L: Patient Pre-Neuropathy Grading Instructions Card 
 
 
 
The following information card will be handed to the patient at the end of treatment 
assessment encounter by the nurse, technologist, or coordinator prior to clinical 
assessment of neuropathy grade. End of treatment neuropathy grading will occur by 
one of the neurologists on the study team who will be blinded to the patient’s 
randomization and treatment allocation at the time of the assessment. 
 
 
 
Thank you for participating in this study.  A doctor will be coming 
in to ask you some questions about your neuropathy.  The doctor 
will use this information to grade your neuropathy.  This doctor will 
not know whether you have been receiving acupuncture or not.  
You may answer all questions.  Please do not provide any 
information about whether you have been receiving acupuncture 
treatments or not until the doctor has completed his/her 
assessment.  Thank you. 
 
 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 49 of 55 
 
Appendix M: CTCAE Neuropathy Grading Form 
OnCore PID: __ __ __ __ __ __ __ __  
Date Completed (mm/dd/yy): __ __ / __ __ / __ __ 
 
PI: Nancy E. Avis, PhD  
Study Number: CCCWFU 97118 
Visit: Baseline Date: (mm/dd/yy) __ __/__ __/__ __   
 
          12 week Date: (mm/dd/yy) __ __/__ __/__ __ 
 
As the clinician grading this patient’s neuropathy, you are blinded from the patient’s 
treatment allocation. You may ask the patient questions to understand the grade of their 
neuropathy but should not ask the patient to reveal their treatment arm. 
 
Please select the appropriate grade of the patient’s neuropathy based on your 
assessment today. 
 
After you have selected the neuropathy grade, you may discuss the patient’s prior 
treatment and prior randomization but do not change your selection. 
 
CTCAE 
Grade of 
neuropathy 
Description of CTCAE 
grade 
Question you may consider 
asking: 
Check the box that 
corresponds to 
neuropathy  grade 
Grade 1 
Asymptomatic; clinical or 
diagnostic observations 
only; intervention not 
indicated 
Do you have any numbness or 
tingling in your hands, fingers, 
feet or toes? 
 
Grade 2 
Moderate symptoms; 
limiting instrumental ADL 
Because of your neuropathy, 
are you not able to clean your 
home, cook meals, shop for 
groceries, or use your 
telephone?  
 
Grade 3 
Severe symptoms; limiting 
self-care ADL; assistive 
device indicated 
Because of your neuropathy, 
are you not able to dress 
yourself, button your shirt or 
pants, bath or shower, cut your 
food or eat? 
 
Grade 4 
Life-threatening 
consequences; urgent 
intervention indicated 
 
 
Grade 5 
 
Death 
 
 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 50 of 55 
 
Appendix N: Chemotherapy Form 
OnCore PID: __ __ __ __ __ __ __ __  
Date Completed (mm/dd/yy): __ __ / __ __ / __ __ 
 
PI:. Nancy E. Avis, PhD  
Study Number: CCCWFU 97118 
INSTRUCTIONS: To be completed at the post treatment visit. Use this form to summarize 
regimen type and changes in regimen during the study 
Total chemotherapy cycles completed: 1 2 
3 
4 
5 
6 
Weeks completed (paclitaxel):  1 2  3  4  5  6  7  8  9  10  11  12 
Was the chemotherapy regimen changed during treatment?  Yes    No    
If yes, was it due to CIPN? Yes    No     Partly (explain):__________________ 
 
Name 
Neurotoxic 
Dose 
Start Date 
of regimen 
(mm/dd/yy
) 
Current 
cycle 
number 
Current 
week of  P, 
C, NP 
Standard 
neurotoxic 
dose? 
(circle) 
AC-T 
Doxorubicin/ 
cyclophosphamide 
followed by weekly 
paclitaxel (12 wk) 
80 mg/m2 
 
 
 
Yes    No* 
TC 
Docetaxel and 
cyclophosphamide 
75 mg/m2 
 
 
 
Yes    No* 
TCH 
Docetaxel/carboplatin/ 
trastuzumab 
75 mg/m2 
 
 
 
Yes    No* 
TCHP 
Docetaxel/carboplatin/ 
trastuzumab +pertuzumab 
75 mg/m2 
 
 
 
Yes    No* 
TH 
Paclitaxel (12 weeks) + 
trastuzumab 
80 mg/m2 
 
 
 
Yes    No* 
mFFX6 
mFOLFOX6 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
mFFX4 
FOLFOX 4 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
FFXI 
FOLFOXIRI 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
FFIX 
FOLFIRINOX 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
mFFIX 
mFOLFORINOX 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
FLOT 
FLOT 
T-50 mg/m2 
O-85 mg 
mg/m2 
 
 
 
Yes    No* 
NG 
Nabpaclitaxel and 
Gemcitabibe 
NP- 125 
mg/m2 
 
 
 
Yes    No* 
CP 
Carboplatin and Paclitaxel 
(CROSS regimen) 
C- AUC2 
P- 50 mg/m2  
 
 
Yes    No* 
 Oth 
Other (specify): 
 
 
 
 
 
Yes    No* 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 51 of 55 
 
*If standard dose was not given during all cycles, complete the table below for all cycles/weeks 
of regimen given: 
Dose Reductions During Chemotherapy Treatment 
Regimen (use 
abbreviation above) 
Cycle 
Week 
Taxane Dose 
(mg/m2) 
Reduction due to 
CIPN? 
 
 
 
 
Yes    No   Other** 
 
 
 
 
Yes    No   Other** 
 
 
 
 
Yes    No   Other** 
 
 
 
 
Yes    No   Other** 
 
 
 
 
Yes    No   Other** 
 
 
 
 
Yes    No   Other** 
 
 
 
 
Yes    No   Other** 
 
 
 
 
Yes    No   Other** 
 
 
 
 
Yes    No   Other** 
 
 
 
 
Yes    No   Other** 
 
 
 
 
Yes    No   Other** 
 
 
 
 
Yes    No   Other** 
 
** If other, please explain: _________________________________________________ 
______________________________________________________________________ 
______________________________________________________________________ 
 
 
Person filling out form: ________________________________________ 
Date (mm/dd/yy): ___ ___/___ ___/___ ___ 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 52 of 55 
 
Appendix O: Acupuncture Treatment Summary Form 
 
OnCore PID: __ __ __ __ __ __ __ __  
Date Completed (mm/dd/yy): __ __ / __ __ / __ __ 
 
PI:. Nancy E. Avis, PhD  
Study Number: CCCWFU 97118 
 
Instructions: Complete this form to summarize the acupuncture treatment.  Appendix 
O does not need to be filled out for participants in the control group.  
 
Session 
Number 
Completed 
Date Completed 
Session 
Duration 
(min) 
Number of 
Needles 
Used 
Were any 
side effects 
reported? 
1 
Yes    No 
__ __ / __ __ / __ __ 
 
 
Yes*    No 
2 
Yes    No 
__ __ / __ __ / __ __ 
 
 
Yes*    No 
3 
Yes    No 
__ __ / __ __ / __ __ 
 
 
Yes*    No 
4 
Yes    No 
__ __ / __ __ / __ __ 
 
 
Yes*    No 
5 
Yes    No 
__ __ / __ __ / __ __ 
 
 
Yes*    No 
6 
Yes    No 
__ __ / __ __ / __ __ 
 
 
Yes*    No 
7 
Yes    No 
__ __ / __ __ / __ __ 
 
 
Yes*    No 
8 
Yes    No 
__ __ / __ __ / __ __ 
 
 
Yes*    No 
  
*If Yes, Please describe any side effects in the table below (and report as an adverse 
event): 
Session 
Number 
Description of symptoms 
Did/Will side 
effects 
necessitate a 
treatment 
change? 
 
 
Yes    No 
 
 
Yes    No 
 
 
Yes    No 
 
 
Yes    No 
 
 
Yes    No 
 
 
Yes    No 
 
 
Yes    No 
 
 
Yes    No 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 53 of 55 
 
 
 
Yes    No 
 
 
Comments: 
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________ 
 
Acupuncturist signature: __________________________________________________ 
 
Date (mm/dd/yy): __ __/__ __/__ __ 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 54 of 55 
 
Appendix P: Acupuncture Expectancy Scale 
 
OnCore PID: __ __ __ __ __ __ __ __  
Date Completed (mm/dd/yy): __ __ / __ __ / __ __ 
 
PI:. Nancy E. Avis, PhD  
Study Number: CCCWFU 97118 
 
Every individual may have different expectations for the effects of acupuncture. If we 
use the following sentences to describe your expectation of acupuncture’s effect on 
your neuropathy after the entire course of acupuncture therapy, how much do you 
agree? For each statement, please circle the closest answer.  
 
 
Not at All 
Agree 
A Little 
Agree 
Moderately 
Agree 
Mostly 
Agree 
Completely 
Agree 
1) My neuropathy will 
improve a lot 
1 
2 
3 
4 
5 
2) I will be able to cope with 
my neuropathy better 
1 
2 
3 
4 
5 
3) The symptoms of my 
neuropathy will disappear 
1 
2 
3 
4 
5 
4) My energy level will 
increase 
1 
2 
3 
4 
5 
 
1. Have you ever had previous experience with acupuncture?  
      No   
      Yes   
2a.  What was your acupuncture for? __________________________________ 
2b.  When did you last engage in acupuncture?  ______________________ 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 55 of 55 
 
Appendix Q: Telephone Screening Form 
 
Date Completed (mm/dd/yy): __ __ / __ __ / __ __ 
 
PI:. Nancy E. Avis, PhD  
Study Number: CCCWFU 97118 
 
Personal Identifiers are NOT to be written on this sheet 
 
Hello, my name is ______________________ and I am calling from the Wake Forest 
School of Medicine for the Acupuncture for Chemotherapy Induced Peripheral 
Neuropathy study.  I am a research assistant who is helping to enroll subjects in clinical 
studies. 
 
If not home/answering machine: 
You called requesting information about our study and I am sorry you are not at home.  I 
would like to speak to you about the study in more detail.  Please call me at 
______________/ or I will try you again later. Thank you. 
 
If home: 
You called requesting information about our study. 
 
You may be eligible to participate in this study, but I will first need to ask you some 
questions now on the telephone to find out if you are likely to be eligible.   
 
First, could you tell me how you found out about the study? [Check all that apply] 
 
 
______newspaper/magazine 
______friend/acquaintance 
______flyer/poster 
______clinic/MD 
______online 
______other, specify 
____________________________________________________ 
 
Let me give you some more information about the study itself.  This is approximately a 
12 week study to see what effects (good and bad) acupuncture has on neuropathy 
(nerve pain or tingling in hands or feet). We are recruiting 22 participants with breast or 
GI cancer for this study.  Some participants will get acupuncture right away and others 
will wait 10 weeks to get acupuncture.  All participants will get some acupuncture.  
Whether you get acupuncture now or later will be randomly determined.  I am going to 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 56 of 55 
 
ask you some questions today to see if you meet initial eligibility for the study.  If you 
are eligible, you will be asked to come into the clinic for an initial visit where you will 
receive a physical exam of your nerve sensations and your medical history will be 
reviewed.  If you are still eligible for our study, you will be asked to complete a 
questionnaire about your neuropathy pain. You will also be scheduled for your next 
study visit that will take place in approximately 1-2 weeks.  
 
At your second study visit, you will receive a standard evaluation of your neuropathy. 
This will take place at the Wake Forest Baptist Health Neurology Clinic. This will involve 
a nerve conduction test, ultrasound imaging, skin biopsy, and blood draw. This will last 
approximately 1.5 hours. 
 
After your second visit, you will be randomized into one of two study groups. You will 
have an equal chance of being placed in either group. The two study groups include an 
acupuncture group and a waitlist group. If you are randomized to the acupuncture 
group, your first acupuncture visit will be scheduled by the Study Coordinator to take 
place within 2 weeks. Acupuncture treatments will take place at the Wake Forest Baptist 
Health Integrative Medicine Clinic Center at 755 Highland Oaks Drive in Winston-
Salem, NC. You will then receive 8 acupuncture treatments (approximately 1x/week) 
over a period of 10 weeks. These can be scheduled at your convenience.  
 
If you are randomized to the waitlist group, you will continue to receive your usual 
medical care and treatments with your clinical providers, but you will not receive any 
acupuncture treatments. After your third study visit, which will be 10-12 weeks from the 
second study visit, you will be offered up to 4 acupuncture treatments at the Wake 
Forest Baptist Health Integrative Medicine Clinic. 
 
You will be provided with parking passes for all study visits. You will also receive a $25 
gift card at study visit 2 and a $75 gift card at study visit 3. These are the two visits that 
involve clinical measures. If you live 60 miles or more from WFBMC, you will receive an 
additional $50 gift card upon completion of the baseline peripheral nerve assessment 
and an additional $50 gift card upon completion of the follow-up assessment. 
 
Now, I need to ask you some questions to find out if you might be eligible to participate. 
 
1. Are you willing to receive acupuncture? 
____ No (not eligible) 
____Yes 
2. Are you able to travel to the Center for Integrative Medicine Clinic for treatments? 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 57 of 55 
 
____ No (not eligible) 
____Yes 
 
3. Do you have breast or GI cancer? 
____ No (not eligible) 
____Yes 
 
4. Do you know the stage of your breast or GI cancer? (check one and confirm that it 
is not currently metastatic) 
____ I  
____ II 
____ III 
____ IV (not eligible) 
____ Unknown 
 
5. Did you complete or are you receiving chemotherapy? 
 
____ No (not eligible) 
 
____ Yes, currently (go to a) 
____ Yes, completed (go to b) 
 
 
a. For patients that are currently receiving chemotherapy: 
i.  How many cycles are you supposed to receive?_____ 
ii. How frequently do you receive tx?_____ 
 
b. For patients who have recently completed chemotherapy: 
i. What day did you complete tx? __/__/__ 
ii. How many weeks was it between each tx? 
_____ 
 
6. What kind of chemotherapy have you received/are you receiving? [Note: If 
respondant says paclitaxel, docetaxel, or b=nabpaclitaxel, she is eligible. If she 
says “other” the treatment eligibility will need to be checked by Dr. Thomas].  

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 58 of 55 
 
____ Paclitaxel 
____ Docetaxel 
____ Nabpaclitaxel 
____ Other (please specify): ________________ 
____ Unknown 
 
7. Are you experiencing numbness and tingling in your hands and feet? 
____ No (not eligible) 
____Yes 
 
8. Do you have a history of history of UNRESOLVED pre-existing peripheral 
neuropathy due to diabetes, HIV, or other conditions? 
____ No  
____Yes (not eligible) 
 
9. Are you pregnant? 
____ No  
____Yes (not eligible) 
 
10. Is the patient eligible? 
____  No, refused to complete screener 
____  No, did not meet eligibility criteria.  EXPLAIN  
 
It looks as though you meet initial eligibility for our study. We will need for you to 
come to the medical where your medical history will be reviewed and your eligibility 
confirmed. If you are still eligible for our study, you will be scheduled for your next 
study visit that will take place in approximately 1-2 weeks. At that visit, you will be 
asked to completed the consent process, complete a questionnaire, receive a 
standard evaluation of your neuropathy (including a nerve conduction test, 
ultrasound imaging, skin biopsy and blood draw) and be told whether you are in the 
waitlist group or will start acupuncture right away. The first acupuncture treatment 
will last approximately 1 hour and subsequent visits will last approximately 30 
minutes. If you are in the waitlist group, you will wait approximately 10 weeks before 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 59 of 55 
 
having another neuropathy assessment and being offered 4 acupuncture treatments 
and during this time we request that you do not receive any acupuncture at all. 
 
11. Are you willing to participate in this study? 
 
____ No  (If no, go to question a) 
 
____ Yes  (If yes, go to question 12) 
 
a. If no, why not? (Check all that apply) 
 
 
____not interested 
 
 
____not enough time 
 
 
____don’t want to be randomized 
 
 
____too many visits 
 
 
____no transportation 
 
 
____call back – need time…. 
 
 
____other, specify    _________________________ 
 
 
 
 
Thank patient for their time and end interview 
 
12.  If you qualify for the study, are you willing to accept random assignment to one of 
the 2 groups?  
 
____ No (STOP, thank woman) 
 
____Yes 
 
 

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 97118 
 
Page 60 of 55 
 
SCHEDULE BASELINE VISIT: 
 
Schedule a baseline visit date and time with woman: 
 
Baseline visit:  ____ ____ - ____ ____ - ____ ____ ____ ____ 
 
 
 
 
       Month 
     Day 
 
         Year 
 
 
 
Visit time:      ____ ____: ____ ____ 
 
AM ____ 
 
 
 
 
      Hour 
  Min  
 
PM ____ 
 
Your first visit will include a meeting with the study coordinator who will tell you all about 
the study, review the study risks and procedures, and confirm additional eligibility. 
Should you have any questions, feel free to call Kelsey Shore and she will assist you in 
any way that she can.   
 
We look forward to seeing you for your first study visit. 
 
Thank you for your time. 
 
Clinic Staff: ______________________________________________________ 
 
MAKE SURE YOU OBTAIN PATIENT'S ADDRESS AND COMPLETE CONTACT 
RECORD 
PLEASE VERIFY THAT STUDY ID ON SCREENER AND CONTACT RECORD 
MATCH