Acupuncture vs. Standard of Care for Induction Intravesical BCG-Related Adverse Events in High-Risk Non-Muscle Invasive Bladder Cancer
Phase: PHASE2
Conditions: Bladder Urothelial Carcinoma In Situ, Recurrent Bladder Urothelial Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage 0is Bladder Cancer AJCC v8, Stage I Bladder Cancer AJCC v8, Superficial Bladder Urothelial Carcinoma
Sponsor: Fred Hutchinson Cancer Center

Protocol RG1007421 
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      version 4/23/2021 
FRED HUTCHINSON CANCER RESEARCH CENTER 
UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE 
SEATTLE CANCER CARE ALLIANCE 
Current version:  4/23/2021 
Previous version:  10/23/2020 
Title of Protocol: 
Acupuncture vs. Standard of Care for Induction Intravesical BCG-related Adverse Events in High-Risk Non-Muscle 
Invasive Bladder Cancer  
Investigators List: 
Investigator 
Professional Title 
Phone Number 
Sarah Psutka, MD, MSc 
Assistant Professor of Urology, UW 
Seattle Cancer Care Alliance 
(206) 598-4294
Heather Greenlee, ND, 
PhD, MPH 
Associate Professor, Fred Hutch  
Associate Professor of Medical Oncology, UW 
Medical Director, Integrative Medicine, SCCA 
(206) 667-4502
Jonathan Wright, MD 
Associate Professor of Urology, UW 
Associate Member, Fred Hutch 
(206) 598-4294
Jonathan Siman, DACM, 
LAc, MS 
Staff Supervising Acupuncturist, SCCA 
(206) 606-1928
Susan Veleber, LAc, MS 
Staff Acupuncturist, SCCA 
(206) 606-1905
Biostatistician: 
Sarah Holt, PhD 
Research Consultant, Urology, UW 
(206) 616-2818
Research Coordinator 
Samia Jannat, MPH 
Research Coordinator 
(206) 598-0061
Sponsor: Early Phase Clinical Research Support Application, Cancer Center Support Grant 
Award ID#  P30 CA015704-44 
FHCRC IRB Approval  
APR 26 2021 
Document Released Date

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PROTOCOL SYNOPSIS 
 
Protocol Title 
Acupuncture vs. Standard of Care for Induction Intravesical BCG-related Adverse 
Events in High-Risk Non-Muscle Invasive Bladder Cancer 
Protocol Number 
RG1007421 
Protocol Sponsor 
CCSG 
Trial Phase 
Phase II 
Trial Type 
Randomized Control Feasibility Trial 
Clinical Indication 
Nonmuscle-invasive bladder cancer (NMIBC) receiving induction Bacillus Calmette–
Guerin (BCG) therapy 
Study Objectives 
The overall objectives of this proposal are to evaluate the feasibility and impact of 
weekly acupuncture compared to a no acupunture (“waitlist”) control group among 
patients being treated with BCG for NMIBC.   
 
Primary objective: To test the feasibility and safety of integrating an outpatient 
acupuncture protocal prior to weekly BCG instillations into the Urology Clinic 
workflow. This will be assessed by trial recruitment, retention, protocol adherence, 
patient/provider feedback and evaluation of adverse events.    
 
Rationale: This objective will measure the extent to which the study intervention 
can be successly incorporated into the intravesical induction BCG regimen. 
Recruitment, retention and adherence is also relevant to inform future power 
calculations for a Phase III clinical trial.  Patient/provider feedback will be used to 
evaluate how the intervention impacts clinical workflow and burden to assess 
potential issues that may impact future implementation and the ability to scale up 
the intervention more broadly.  Lastly, this objective will determine the safety and 
tolerability of adjuvant acupuncture in patients undergoing induction intravesical 
BCG for NMIBC. 
 
Secondary objectives: To test whether acupuncture may help patients complete 
the 6-weekly instillations of intravesical BCG. This will be assessed through a 
patient’s completion of BCG regimen, patient-reported outcomes of urinary 
symptoms and overall quality of life (as measured by the EORTC QLQ-NMIBC-24(1) 
and  EORTC QLQ-C30(2) scales, respectively) and quantification of medication use 
for symptom management.  
 
Rationale: A goal of this study is to identify an adjunctive therapy that can help 
patients complete the induction BCG through reduction of urinary and pelvic 
treatment side effects. These data will provide both direct and indirect measures of 
acupuncture as a potential intervention tool and inform future power calculations 
for a Phase III clinical trial. 
Study Design 
Randomized Control Feasibility Trial 
Population 
45 BCG- adults from the UWMC Department of Urology who are scheduled to 
receive 6 weekly doses of intravesical BCG. Eligibility criteria includes 1) age 18 
years or older, 2) English-speaking, 3) diagnosis of American Urological Association 
(AUA) high-risk NMIBC, including high grade (HG) pT1 (invading only the lamina 
propria of the bladder), recurrent HG pTa (superficial tumors), HG pTa >3cm in size 
or multifocal, any carcinoma in situ, any variant histology, any lymphovascular 
invasion, and HG prostatic urethral involvement(3) 4) have not received 
acupuncture in the previous 3 months, and 5) willing and able to participate in trial 
activities. 
Primary Endpoints 
1. Feasibilty, as assessed by recruitment, retention, and adherence to the 
acupuncture protocol. 
2. Safety and tolerability of acupuncture protocol (physician reported CTCAE v5.0 
adverse events). 

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Secondary Endpoints 
1. BCG treatment adherence, interruptions, dose-reductions, completion of 
therapy as intended 
2. Patient reported urinary symptoms (EORTC  QLQ-NMIBC-24) and patient-
reported quality of life (EORTC-QLQ-C30) 
3. Use of medications for symptom management per patient report and per 
prescription 
Type of control 
Waitlist arm – receives no acupuncture prior to BCG  
Investigation Drug 
N/A 
Dose 
Acupuncture: 6 weekly treatments with 30 minute needle retention 
Route of administration 
Acupuncture: filiform needle insertion 
Regimen 
6 weekly sessions treatments prior to BCG 
Trial Blinding 
None 
Treatment Groups  
Arm A: Acupuncture Intervention – Dose given pre-BCG treatment with standard of 
care symptom management. 
Arm B: Waitlist Control Arm – No dose given pre-BCG treatment with standard of 
care symptom management and 4 coupons for acupuncture after study completion. 
Treatment Schedule 
Once weekly for six weeks 
Efficacy Assessments 
Baseline 
Weekly at BCG treatment 
1 week following last treatment 
Number of trial subjects 
45 
Estimated duration of trial 
12 months 
Duration of Participation 
Eight weeks 
 
 
 
 

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ABBREVIATIONS 
 
NMIBC 
Nonmuscle-invasive bladder cancer 
BCG 
Bacillus Calmette–Guerin 
QOL 
Quality of life 
AUA 
American Urological Association 
OAB 
Overactive bladder 
PTNS 
Percutaneous Tibial Nerve Stimulation 
UWMC 
University of Washington Medical Center 
HG 
High grade 
pT1 
Invading only the lamina propria of the bladder 
HG pTa 
Superficial papillary bladder tumors, noninvasive 
TCM 
Traditional Chinese Medicine 
GMP 
Good Manufacturing Practices 
AAMI 
Association for the Advancement of Medical Instrumentation 
ISO 
International Organization for Standardization 
CE Mark 
European Conformity Marking 
WHO 
World Health Organization 
EA 
Electroacupuncture 
FDA 
U.S. Food and Drug Administration 
NCCAOM 
National Certification Commission for Acupuncture and Oriental Medicine 
SCCA 
Seattle Cancer Care Alliance 
BCAN PSN 
Bladder Cancer Advocacy Network Patient Survey Network 
SOC  
Standard of care 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
1.0 
GENERAL INFORMATION .................................................................................................................................................. 8 
1.1 
Protocol Title ........................................................................................................................................................ 8 
1.2 
Sponsor Information ............................................................................................................................................ 8 
1.3 
Investigator Information ...................................................................................................................................... 8 
1.4 
Contractors and Consultants for the Study.......................................................................................................... 8 
2.0 
INTRODUCTION TO THE PROTOCOL ................................................................................................................................. 8 
2.1 
Introduction ......................................................................................................................................................... 9 
2.2 
Preclinical Data .................................................................................................................................................... 9 
2.3 
Clinical Data to Date ............................................................................................................................................ 9 
2.4 
Study Intervention ............................................................................................................................................... 9 
2.5 
Dose Rationale ................................................................................................................................................... 10 
2.6 
Risks/Benefits..................................................................................................................................................... 10 
3.0 
OVERVIEW OF CLINICAL TRIAL ........................................................................................................................................ 10 
3.1 
Study Objectives ................................................................................................................................................ 10 
3.2 
Study Population ................................................................................................................................................ 10 
3.3 
Study Design ...................................................................................................................................................... 11 
3.5 
Name of Sponsor/Funding Source ..................................................................................................................... 15 
4.0 
SAFETY CONSIDERATIONS ............................................................................................................................................... 15 
4.1 
Stopping Rules ................................................................................................................................................... 15 
5.0 
SUBJECT ELIGIBLITY ......................................................................................................................................................... 15 
5.1 
Inclusion Criteria ................................................................................................................................................ 15 
5.2 
Exclusion Criteria ............................................................................................................................................... 15 
6.0 
SUBJECT REGISTRATION .................................................................................................................................................. 17 
7.0 
TREATMENT PLAN ........................................................................................................................................................... 17 
7.1 
Treatment Plan Overview .................................................................................................................................. 17 
7.2 
Waitlist Control .................................................................................................................................................. 18 
7.3 
Concomitant Medication, Interruption of Therapy, and Supportive Care Guidelines ....................................... 18 
7.4 
Duration of Therapy ........................................................................................................................................... 19 
7.5 
Duration of Follow-Up ....................................................................................................................................... 19 
7.6 
Dosing Delays/Dose Modifications .................................................................................................................... 19 
7.7 
End of Treatment (EOT) Visit Schedule and Procedures .................................................................................... 19 
8.0 
SUBJECT EVALUATION..................................................................................................................................................... 19 
8.1 
On-Study Clinical Evaluations ............................................................................................................................ 19 
9.0 
SUBJECT DISCONTINUATION OF ACTIVE TREATMENT .................................................................................................... 22 
10.0 
CONCOMITANT MEDICATIONS ....................................................................................................................................... 22 
11.0 
ADVERSE EVENTS ............................................................................................................................................................ 23 
11.1 
Adverse Event .................................................................................................................................................... 23 
11.2 
Serious Adverse Event ....................................................................................................................................... 23 

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11.3 
Unexpected Adverse Event ................................................................................................................................ 23 
11.4 
Monitoring and Recording Adverse Events ....................................................................................................... 24 
11.5 
Grading Adverse Event Severity ......................................................................................................................... 24 
11.6 
Attribution of an Adverse Event ........................................................................................................................ 24 
11.7 
Adverse Event Recording Period ........................................................................................................................ 24 
11.8 
Adverse Event Reporting Requirements ............................................................................................................ 24 
12.0 
DATA AND SAFETY MONITORING PLAN .......................................................................................................................... 25 
13.0 
DATA MANAGEMENT/CONFIDENTIALITY ....................................................................................................................... 25 
14.0 
STATISTICAL CONSIDERATIONS ....................................................................................................................................... 25 
14.1 
Study Design ...................................................................................................................................................... 25 
14.2 
Primary/Secondary Endpoints/Hypotheses and Analytical Methods ................................................................ 25 
14.3 
Sample Size and Power ...................................................................................................................................... 26 
14.4 
Analysis of Covariates ........................................................................................................................................ 26 
14.5 
Ethnic and Gender Distribution Chart ................................................................................................................ 26 
14.6 
Indications for Stopping ..................................................................................................................................... 27 
15.0 
INVESTIGATOR OBLIGATIONS ......................................................................................................................................... 27 
16.0 
REFERENCES .................................................................................................................................................................... 28 
17.0 
APPENDICES .................................................................................................................................................................... 29 
APPENDIX A – Study Schema ............................................................................................................................................... 30 
APPENDIX B – ECOG Performance Status Scale .................................................................................................................. 31 
APPENDIX C: Acupoint Location Diagram ............................................................................................................................ 32 
 ........................ 32 

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APPENDIX D: STUDY CALENDAR .......................................................................................................................................... 33 
 
 
 
 

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1.0 
GENERAL INFORMATION 
 
The standard of care treatment for high-risk nonmuscle-invasive bladder cancer (NMIBC) is 6-weekly instillations of 
intravesical Bacillus Calmette-Guerin (BCG). However, patients frequently experience treatment interruptions and/or 
discontinuation due to urinary and pelvic side effects of this treatment. Strategies to minimize BCG-associated toxicity are 
needed to improve treatment adherence and subsequent NMIBC clinical outcomes. We will evaluate the feasibility and 
effects of acupuncture compared to a waitlist control on bladder symptoms and overall quality of life, treatment 
adherence, and safety and tolerability among patients treated with BCG for NMIBC. NMIBC patients (n=45) will be recruited 
from the UWMC Uro-oncology Clinic. Baseline data collection will include demographics, clinical characteristics, bladder 
cancer symptoms, quality of life (QOL), and medication use. Patients are randomized 2:1 to acupuncture (Arm A) and a 
waitlist control (Arm B). Patients in Arm A receive 6 weekly acupuncture treatments prior to BCG instillation. Patients in 
Arm B receive coupons for free acupuncture after the completion of treatment. All patients will receive standard symptom 
management. Follow-up data collection includes baseline measures plus healthcare utilization assessments. The primary 
objective tests the feasibility, safety and tolabilty of outpatient acupuncture prior to weekly BCG instillations, as assessed by 
trial recruitment, retention, and adherence to the protocol.  Secondary objectives are to compare completion of BCG 
regimin, urinary symptoms, QOL and use of medications for symptom management between arms. Study results will be 
used to inform the design of a large-scale trial to test the effect on acupuncture in improving NMIBC treatment adherence.    
 
1.1 
Protocol Title 
Acupuncture vs. Standard of Care for Induction Intravesical BCG-related Adverse Events in High-Risk Non-Muscle 
Invasive Bladder Cancer  
 
1.2 
Sponsor Information 
Early Phase Clinical Research Support Application, Cancer Center Support Grant 
 
1.3 
Investigator Information 
Sarah P. Psutka MD, MSc (PI) 
Assistant Professor of Urology, Department of Urology, Division of Urologic Oncology, University of Washington 
School of Medicine, Seattle Cancer Care Alliance  
 
Heather Greenlee, ND, PhD, MPH (Co-I) 
Associate Member, Public Health Sciences and Clinical Research Divisions, Fred Hutchinson Cancer Research Center  
Associate Professor of Medicine, Division of Medical Oncology, University of Washington School of Medicine 
Medical Director of the Integrative Medicine Program, Seattle Cancer Care Alliance (SCCA) 
 
Jonathan Wright, MD (Co-I) 
Associate Professor of Urology, Department of Urology, Division of Urologic Oncology, University of Washington 
School of Medicine 
Associate Member, Public Health Sciences, Fred Hutchinson Cancer Research Center 
 
Sarah Holt, PhD (Co-I)  
Biostatistician, Research Consultant, University of Washington School of Medicine Department of Urology 
 
1.4 
Contractors and Consultants for the Study  
 
Jonathan Siman, DACM, LAc, MS, Staff Lead Acupuncturist, Seattle Cancer Care Alliance  
 
Susan Veleber, LAc, MS, Staff Acupuncturist, Seattle Cancer Care Alliance  
 
Samia Jannat, Research Coordinator  
 
 
2.0 
INTRODUCTION TO THE PROTOCOL 
 

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2.1 Introduction 
In 2019, the American Cancer Society estimates that approximately 80,470 Americans will receive new diagnoses of bladder 
cancer, of which approximately 75% will be new diagnoses of nonmuscle-invasive bladder cancer (NMIBC).(4) As per the 
American Urological Association (AUA) Guidelines, the cornerstone of management of high-risk, NMIBC is an induction 
course of 6 weekly instillations of intravesical Bacillus Calmette–Guerin (BCG) treatment following resection of the tumor. 
(5) Unfortunately, nearly 70% of patients receiving BCG report severe adverse events(6) and approximately 40% of patients 
receiving induction BCG therapy necessitate treatment interruptions secondary to local or systemic adverse events 
including pelvic pain, dysuria, severe urgency, frequency, urge incontinence, nocturia, and/or infectious complications.(7) 
These treatment-associated symptoms are problematic, resulting in decreased ability to adhere to the full course of 
treatment, which is associated with decreased clinical efficacy of BCG in reducing the risk of recurrence and progression of 
bladder cancer, as well as severely negatively impacting patients’ quality of life. Consequently, there is a need for adjunctive 
therapies to minimize BCG-associated side effects in order to maximize the likelihood that patients will be able to adhere to 
the full course of therapy. 
 
Current approaches to managing BCG treatment side effects:  
Many of the side effects associated with induction intravesical BCG mirror those of overactive bladder syndrome (OAB). 
Commonly, the irritiative voiding complaints are managed symptomatically with anticholinergic medications, while bladder 
pain and dysuria are treated with local analgesics, antibiotics, nonnarcotic pain medications and narcotics, which may or 
may not be successful in mitigating the severe adverse events associated with intravesical BCG instillatio, and which, 
furthermore, may be associated with dose-limiting side effects themselves. Indeed, the most commonly prescribed 
anticholinergic, oxybutynin, was demonstrated to be associated with an increase in lower urinary tract symptoms 
compared to placebo in a recent randomized controlled trial.(8) 
  
2.2 Preclinical Data 
Acupuncture as a potential treatment to increase BCG treatment adherence:  
Recently, the use of acupuncture has been shown to be clinically effective in minimizing the severity of OAB symptoms, 
resulting in decreased medication use and decreased need for surgical treatment of OAB, while simultaneously having an 
excellent safety and tolerability profile.(9-14) We hypothesize that acupuncture may be a viable approach to decrease the 
symptoms akin to OAB secondary to intravesical BCG instillations for high-risk bladder cancer.   
Data from animal studies suggest several physiologic mechanisms of action of the beneficial effects of acupuncture on 
overactive bladder (OAB) syndrome, including modulating the voiding reflex by decreasing intravesical (bladder) pressure 
and facilitating storage through inhibiting bladder muscle motor activity.(9) (12) (15) Human trials in OAB show that 
acupuncture is associated with improvements in urgency, frequency, nocturia, incontinence, quality of life and some 
objectively measured improvements in urodynamic testing.(9, 10, 16) Additionally, acupuncture has been shown to have 
comparable effects to anticholinergic drugs in the reduction of micturition episodes in 24 hours, increased void volumes 
and reduction in OAB symptom score with fewer reported side-effects. (9, 10, 16) Percutaneous Tibial Nerve Stimulation 
(PTNS), an established FDA-approved second-line treatment option for refractory OAB, is derived from acupuncture theory 
and techniques. 
 
2.3 Clinical Data to Date 
To our knowledge, there are no specific data on the efficacy of acupuncture on improving treatment adherence to 
induction intravesical BCG. However, as noted above, data on the effect of acupuncture in other related clinical conditions 
suggest that this is a reasonable application of acupuncture to pursue. Data from animal studies suggest several physiologic 
mechanisms of action of the beneficial effects of acupuncture on overactive bladder (OAB) syndrome, including modulating 
the voiding reflex by decreasing intravesical (bladder) pressure and facilitating storage through inhibiting bladder muscle 
motor activity.(9, 12) (15) Human trials in OAB show that acupuncture is associated with improvements in urgency, 
frequency, nocturia, incontinence, quality of life and some objectively measured improvements in urodynamic testing.(9, 
10, 16) Additionally, acupuncture has been shown to have comparable effects to anticholinergic drugs in the reduction of 
micturition episodes in 24 hours, increased void volumes and reduction in OAB symptom score with fewer reported side-
effects. (9, 10, 16) Percutaneous Tibial Nerve Stimulation (PTNS), an established second-line treatment option for refractory 
OAB, is derived from acupuncture theory and techniques. 
 
2.4 Study Intervention 
Acupuncture is a medical intervention in which fine metallic needles are inserted into anatomical locations of the body to 
stimulate the peripheral and the central nervous system. 

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2.5 Dose Rationale 
Acupuncture dose. Clinically, the number of acupuncture treatments required depends on the condition being treated and 
the individual response to acupuncture. The standard course of acupuncture treatment is one to two sessions a week for 
four to ten weeks.(17) Most acupuncture trials in the US have a dose of one to two treatments per week for six to ten 
weeks. Given the standard dosing frequency of BCG instillations is once per week for six weeks, which is also a reasonable 
treatment frequency for acupuncture, the acupuncture dose is once per week for six weeks. 
 
2.6 Risks/Benefits 
Acupuncture is generally considered safe(18) when administred by a trained licensed acupuncturists. The risks of 
acupuncture are few and include minor bruising, bleeding, pain, redness, itchiness, and/or local allergic reactions at the 
insertion site(s). In rare instances, syncope, infection, or organ puncture can occur.(13) 
 
3.0 
OVERVIEW OF CLINICAL TRIAL 
 
The overall objective of this proposal is to evaluate the feasibility and impact of 6 weekly acupuncture treatments 
compared to a waitlist control on patient-reported bladder symptoms and overall quality of life, treatment adherence, and 
safety and tolerability among patients being treated with BCG for NMIBC.   
 
3.1 Study Objectives 
 
3.1.1 
Primary Objectives 
Primary objective: To test the feasibility and safety of integrating an outpatient acupuncture 
protocal prior to weekly BCG instillations into the Urology Clinic workflow. This will be assessed by 
trial recruitment, retention, protocol adherence, patient/provider feedback and adverse events.    
 
 
To achieve this objective, we will: 
1. Evaluate the recruitment, rentention and protocal adherence to acupuncture treatment.  
2. Survey clinic staff regarding the impact of this intervention on clinical workflow, delays, and 
clinic burden.  
3. Measure physician reported CTCAE v5.0 adverse events specific to acupunture.  
 
3.1.2 
Secondary Objectives 
To test whether acupuncture may help patients complete the 6-weekly instillations of intravesical 
BCG. This will be assessed through a patient’s completion of BCG regimen, patient-reported 
outcomes of urinary symptoms and overall quality of life (as measured by the EORTC QLQ-NMIBC-
24(1) and  EORTC QLQ-C30(2) scales, respectively) and quantification of medication use for symptom 
management. 
 
 
To achieve this objective, we will: 
1. Compare rates of BCG treatment adherence between arms, as measured by treatment 
completion, treatment interruptions, and tolerance of treatment retention as measured by 
time retained, and dose reduction.  
2. Compare patient-reported outcomes of urinary symptoms and overall quality of life 
between arms, as measured by the EORTC QLQ-NMIBC-24 and  EORTC  QLQ-C30 scales, 
respectively.  
Quantify and compare use of medications for symptom management in patients in the 
intervention and waitlist control arms, as measured bymedication use questionnaire. 
3.2 Study Population 
The University of Washington Medical Center (UWMC) Department of Urology Clinic administers BCG to high-risk NMIBC 
patients receiving either induction or maintenance therapy approximately 40-50 times monthly. We will recruit 45 BCG- 
adults from the UWMC Department of Urology who are scheduled to receive 6 weekly doses of intravesical BCG. Patients 

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will be indicated to receive BCG by their primary treating urologist following evaluation of histology from bladder biopsy 
and/or transurethral resection of bladder tumor tissue, as part of guideline-based standard of care.  
 
Eligibility criteria includes 1) age 18 years or older, 2) English-speaking, 3) diagnosis of American Urological Association 
(AUA) high-risk NMIBC, including high grade (HG) pT1 (invading only the lamina propria of the bladder), recurrent HG pTa 
(superficial tumors), HG pTa >3cm in size or multifocal, any carcinoma in situ, any variant histology, any lymphovascular 
invasion, and HG prostatic urethral involvement(3), 4) have not received acupuncture in the previous 3 months, and 5) 
willing and able to participate in trial activities. A member of the research team will manually review weekly schedules of 
full-time uro-oncology faculty (n=6) and fellows (2) to identify patients who meet eligibility criteria as potential study 
subjects. Patients eligible to participate in the study will be approached by PI/Attending Physician/Advanced Practice 
Provider/ in the clinic following their post-operative visit during which pathology is discussed and they are counseled 
regarding BCG induction therapy. Study details will be provided to the patient and informed consent will be discussed at 
this time. If informed consent is granted, the patient will enter into this trial. Patients who provide consent will be 
randomized 2:1 to receive weekly acupuncture pre-BCG treatment plus standard of care symptom management (Arm A) or 
to the waitlist control arm (Arm B), standard of care symptom management plus four coupons for acupuncture after study 
completion. 
 
3.3 Study Design 
Baseline data collection. Prior to initiation of induction BCG, baseline data will be collected at the time of randomization, or 
at a subsequent baseline study visit or via the phone,email or mailing, depending on patient preference.  
 
Baseline data collection will include 1) clinicopathologic and demographic data; 2) a patient-reported voiding and symptoms 
assessment using the EORTC QLQ-NMIBC-24 Survey, a validated quality of life questionnaire assessing the domains of 
urinary symptoms including OAB symptoms, malaise, intravesical treatment issues, future worries, bloating/flatulence, 
sexual function/intimacy, concerns regarding risk to partners related to therapies designed specifically for patients with 
NMIBC; 3) patient-reported quality of life as assessed via the EORTC-QLQ-C30 Survey, a validated generic quality of life 
instrument assessing the domains of depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, 
and ability to participate in social roles and activities ranked on a 4-point Likert scale with an additional 7-point rating scale 
for overall health and quality of life; 4) current medication use; and 5) current use of complementary, alternative and 
integrative therapies 6) acupuncture expectancy and treatment preference. 
 
Induction BCG procedures. Patients undergoing induction BCG present once weekly to the UWMC Urology Clinic. They are 
routinely requested to present 1 hour prior to their scheduled intravesical instillation at which time a urinanalysis is 
obtained to rule out gross hematuria or concern for urinary tract infection. They are then brought into the clinic exam room 
where a foley catheter is placed by a nurse or advanced practice provider. The bladder is emptied completely. Then the BCG 
solution (50mL) is instilled into the catheter over 1-3 min by gravity. The catheter is removed, and the patient discharged 
from clinic. Patients are instructed to attempt to maintain the medication in their bladder (avoid voiding) for two hours, at 
which time they may void the medication normally with appropriate precautions to ensure deactivation of the live 
attenuated vaccines. This procedure is repeated weekly for six weeks. If patients report gross blood in the urine or are 
found to have a urinalysis consistent with urinary tract infection at the time presentation, or are having severe symptoms of 
cystitis or bladder pain, treatment is deferred for that week in consultation with their treating physician.  
    
Arm A: Acupuncture intervention. After providing a urinary sample for a screening urinanalysis prior to BCG treatment, 
patients randomized to the acupuncture intervention will be escorted to a consultation room where they will meet with the 
study acupuncturist. Over the next 45-60 minutes the following protocol will be implemented:   
 
Position. The patient will lay in a comfortable position on a portable acupuncture table. Specifically, the patient will lay in 
the lateral recumbent position on their preferred side.   
 
Acupoints. Standard techniques for point location(19) will be utilized and Clean Needle Technique(20) will be followed. See  
Figure 2 for acupoint locations. The acupuncture points will be needled unilaterally at KI3, KI7, KI10, and SP6 on the lower 
leg. On the contralateral sided LI11 and LU7 will be needled on the upper extremity. The points BL31, BL32, and BL33 will be 
needled bilaterally near the sacrum. The points Yin Tang (EX-HN3) and DU20 will be needled on the midline and auricular 
Shen Men will be needled unilaterally on the same side as the upper limb points. There will be a total of 15 needle sites. 
Electro-stimulation will be administered to SP6 and KI7 at 1-10mA with a frequency of 20Hz. Needles will be retained for 30 
minutes. Specific acupoint selection is based on previously published studies,(9, 10, 16) indications according to Traditional 

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Chinese Medicine (TCM) theory(19) and current understanding of innervation and neuromodulation of acupoints.(12),(15) 
After the 30 minute-long treatment, the needles will be removed and the patient will be moved to the treatment room 
where BCG will be administered according to standard protocol.  
 
Acupuncture needles. 32-40-gauge x 30mm-40mm Seirin acupuncture needles will be used on all acupoints. The needles 
and guide tubes are individually packaged and sterile. The manufacturer of Seirin acupuncture needles conforms to with 
GMP, AAMI (American National), ISO 9002, CE Mark (European Common Market), and WHO (World Health Organization) 
guidelines for quality and safety.(21) 
 
Electroacupuncture. (EA) machines used will be FDA compliant medical devices.(22-24) 
Licensing and credentialing of acupuncturists: Acupuncture treatments will be performed by Washington State licensed 
acupuncturists with National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM) certification. 
Study acupuncturists will be credentialed by the Seattle Cancer Care Alliance (SCCA) and UWMC to provide acupuncture to 
oncology patients and will be supervised by the Lead SCCA Acupuncturist. 
 
Symptom management. All patients will receive standard of care medications to treat symptoms (e.g. anticholinergics such 
as oxybutynin, tolterodine, darifenacin, solifenacin, trospium, fesoterodine; Beta-3 adrenergic agonists such as mirabegron, 
local analgesics such as phenazopyridine, narcotic medications such as oxycodone if necessary, nonnarcotic medications 
such as Tylenol and non-steroidal anti-inflamatory medications) as indicated. 
 
Arm B: Waitlist control arm. To minimize differences in experience between the acupuncture intervention and waitlist 
control arms, patients in the waitlist control arm will be escorted to the same Consultation room where the acupuncture is 
performed and asked to lie in a comfortable position (similar to Arm A) prior to their intravesical therapy for an identical 
period of time before being moved to a treatment room for intravesical instillation of BCG, according to the standard 
protocol detailed above. At the conclusion of the trial participants in the waitlist control arm will receive coupons to receive 
4 free acupuncture appointments. All patients will receive standard of care to treat symptoms (e.g. narcotic and 
nonnarcotic medications, local analgesics, anticholinergic medications) as indicated. 
 
Follow-up data collection. On a weekly basis, prior to BCG instillation and adjunctive acupuncture therapy (if applicable), 
patients in both the intervention and waitlist control arms will be assessed using the following metrics:  
Week 1 
EORTC-QLQ-NMIBC-24 
EORTC-QLQ-C30 
Medication Journal 
Assessment of complementary, alternative, and integrative therapies 
Acupuncture expectancy and treatment preference 
Week 2 
EORTC-QLQ-NMIBC-24 
EORTC-QLQ-C30 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the prior week 
Medication Journal  
Week 3 
EORTC-QLQ-NMIBC-24 
EORTC-QLQ-C30 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the prior week 
Medication Journal 
Week 4 
EORTC-QLQ-NMIBC-24 
EORTC-QLQ-C30 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the prior week 
Medication Journal  
Week 5 
EORTC-QLQ-NMIBC-24 
EORTC-QLQ-C30 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the prior week 
Medication Journal 
Week 6 
EORTC-QLQ-NMIBC-244 
EORTC-QLQ-C30 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the prior week 
Medication Journal  
Week 7 
EORTC-QLQ-NMIBC-24 

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EORTC-QLQ-C30 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the prior week 
Medication Journal  
Follow-up-assessment of complementary, alternative, and integrative therapies 
Exit questionnaire 
 
Additionally, weekly, healthcare utilization will be measured by the number of patient phone calls and eCare messages 
regarding intravesical-therapy related complaints and unplanned presentations to the emergency room, clinic, and their 
local providers.   
 
BCG Treatment adherence to each successive BCG therapy will be measured via receipt of complete induction course 
(yes/no), need for delay of therapy (if yes, by how long), need for decrease in BCG-dose, timing of need for decrease in 
BCG-dose.   
 
Intravesical therapy dwell time will be measured by time from BCG instillation to time of first void. Patients will be 
requested to either text or call the research coordinator for the study upon void. If the research coordinator has not heard 
from the patient within 4-5 hours of their clinical appointment, they will contact the patient by phone call, text, or email to 
inquire as to what time the patient voided following BCG instillation. 
 
Adverse events will be recorded on a weekly basis using the CTCAE v5. Patients in the acupuncture arm will be surveyed 
weekly prior to acupuncture treatments regarding side effects and potential adverse events associated with the 
intervention using a standardized symptom assessment form.   
 
Intervention implementation metrics will be assessed via the following:   
 
Burden to physicians/healthcare providers will be assessed at bimonthly intervals via surveys on the burden of the 
acupuncture procedure to clinic workflow, delays in providing care, and overall assessments of trial implementation 
success.   
 
Timing of visits will be assessed via recording of time of presentation, time of initiation of therapy, and time leaving the 
clinic.   
 
3.3.1 
Primary Endpoint 
Objective:  To demonstrate trial feasibility,  impact of integrating outpatient acupuncture 
(exposure) prior to weekly BCG instillations into the Urology Clinic workflow, and access safety of 
treatment protocal. To evaluate the safety and tolerability of acupuncture compared to best 
supportive care practices in patients with high-risk NMIBC undergoing induction intravesical BCG, 
as measured by physician reported CTCAE v5.0 adverse events. 
 
Analysis plan: The feasibility outcome will be assessed via the following measures:   
1. Compare proportion of patients successfully recruited to the trial from those 
eligible. 
2. Compare proportion of recruited patients successfully retained in the experimental 
(acupuncture) and control arms. 
3. Compare adherence to the protocol (completion of acupuncture treatments in the 
experimental arm). 
4. Describe clinic-staff’s responses to surveys assessing the healthcare burden of this 
protocol and compare timing of patient’s experience within the clinic, time spent 
undergoing the acupuncture therapy for the experimental arm. 
5. Track adverse events associated with acupuncture therapy in the experimental arm 
as completed by a provider administered standardized symptom form across weeks 
of therapy and describe any complications or adverse effects of the therapy. 
 
Expected results and interpretation: We hypothesize that the study is feasible and can 
be integrated into the clinical workflow of the UWMC Urology clinic with relatively 
minimal disturbance of the current procedures given that we will be using a consultation 

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room which is currently not utilized for clinical visits during the day. Additionally, given 
that patients are requested to be in clinic 1 hour prior to their BCG instillation, we do 
not anticipate that this study will place further undue time burden upon patients. We do 
anticipate problems with study recruitement and retainment in this population and that 
these patients will have a high level of protocal adherence. We hypothesize that the 
acupuncture procedures in the experimental arm will be well tolerated without clinically 
meaningful adverse events other than minimal bruising and occasionally soreness at the 
needling site.(13, 14) 
 
3.3.2 
Secondary Endpoints  
Objective: To demostrate impact of acupuncture on BCG adherence on direct and indirect measures 
that include evaluation of BCG protocal experience, patient-reported outcomes of overall quality of 
life and urinary symptoms, and quantification of medication usage for symptom management.   
 
Analysis plan:  
1. Compare Rates of BCG instillation adherence (out of a possible planned six 
treatments), treatment interruptions, weeks missed, intravesical BCG dwell times 
(as measured in minutes), and requirement for dose reductions between the 
acupuncture and control arms. 
2. Compare the responses of patients in the experimental and control arms to the 
EORTC-QLQ-NMIBC-24 symptom index, which was specifically designed to assess 
bladder and bowel symptoms for patients with NMIBC including assessments of 
impact of intravesical therapy, and the EORTC-QLQ-C30 , which assesses general 
quality of life. These assessments will be compared between patients by week of 
treatment (from week 1 to week 6).     
3. Median weekly pill counts standardized by dosage across medication types will be 
compared between the experimental and control arms by week of therapy. Patients 
will be given a weekly medication diary and asked to record the number of 
pills/doses taken per day of specific medications which are administered for bladder 
symptom management while undergoing intravesical therapies. This pill diary will 
include topical analgesics such as phenazopyridine, anticholinergic medications, 
Beta-3 adrenergic receptor agonists (e.g. mirabegron), systemic pain medications 
including acetaminophen, nonsteroidal anti-inflammatory agents, narcotics, and 
other naturopathic therapies targeted at symptoms of dysuria, bladders spasms, 
and pelvic pain.   
 
Expected results and interpretation: We hypothesize that patients in the experimental 
group will have higher proportion finishing BCG regimen, with less interuptions and 
fwere required dose reductions of BCG. We hypothesize that patients in the 
experimental group will report similar general quality of life and NMIBC-specific 
symptoms initially. However, as patients advance in their treatments from 1 to 6 weeks, 
we anticipate that patients in the experimental arm will endorse improved quality of life 
and lower levels of bladder/bowel symptoms compared to the control arm. 
Furthermore, we predict that patients randomized to the experimental arm will have 
higher rates of protocol retention, treatment adherence, and median intravesical dwell 
times of the BCG at each treatment. We hypothesize that patients in the experimental 
arm will report taking lower amounts of adjunctive medications for bladder-relates 
symptoms and that the discrepancy in adjunctive treatments taken will increase across 
the 6 weeks of therapy as the BCG-related symptoms are expected to increase with each 
subsequent intravesical dose of BCG.   
 
 

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3.4  Estimated Accrual 
The University of Washington Medical Center (UWMC) Department of Urology Clinic administers BCG to high-risk NMIBC 
patients receiving either induction or maintenance therapy approximately 40-50 times monthly. We will recruit 45 BCG- 
adults from the UWMC Department of Urology who are scheduled to receive 6 weekly doses of intravesical BCG. 
 
3.5 Name of Sponsor/Funding Source 
Sponsor: Early Phase Clinical Research Support Application, Cancer Center Support Grant 
Award ID#  P30 CA015704-44 
 
4.0 
SAFETY CONSIDERATIONS 
 
4.1 Stopping Rules 
This trial does not contain stopping rules. 
Patients will be monitored for BCG-related toxicity as per standard of care practice. Modifications to BCG dosing and 
intervals between treatment will be made on a per-patient basis per usual care.  
 
 
5.0 
SUBJECT ELIGIBLITY 
 
5.1 Inclusion Criteria  
5.1.1 
Demographic Data 
1) 18 years of age or older  
2) English-speaking 
5.1.2 
Disease Related Criteria 
3) Diagnosis of American Urological Association (AUA) high-risk NMIBC, including high grade (HG) 
pT1 (invading only the lamina propria of the bladder), recurrent HG pTa (superficial tumors), HG 
pTa >3cm in size or multifocal, any carcinoma in situ, any variant histology, any lymphovascular 
invasion, and HG prostatic urethral involvement(3)  
4) Diagnosis with urothelial carcinoma (primary histologic subtype), localized ot the bladder, in the 
absence of nodal or other visceral metastases.  
5) Patients who have been indicated for induction intravesical BCG in shared-decision-making with 
their primary urologist. 
5.1.3 
Prior/Current Related Criteria 
6) Have not received acupuncture in the previous 3 months.  
5.1.4 
Accessibility Criteria 
7) Access to phone for study contacts. 
8) Willing and able to participate in trial activities 
 
5.1.5 
Clinical/Laboratory Criteria 
9) Platelets: 20,000/ μL or greater 
10) ANC: 500 cells/μL or greater 
5.1.6 
Ability to understand and the willingness to sign a written informed consent document. 
11) Able to understand and willing to sign written informed consent in English. 
 
5.2 Exclusion Criteria 
5.2.1 
Receipt of prior therapy 
Subjects who have had intravesical or systemic chemotherapy or radiation therapy  for bladder 
cancer or for other malignancies prior to entering the study. 

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5.2.2 
Subjects may not be receiving other investigational agents or other combined intravesical 
therapies. 
Subjects who are indicated to receive other intravesical agents or therapies concurrently with BCG 
will be excluded.  
 
5.2.3 
Disease-specific criteria 
Subjects who have muscle-invasive bladder cancer, radiographic evidence of lymph node metastases 
or metastatic disease involving other organs including brain metastases.  
Patients with predominant histology other than urothelial carcinoma of the bladder who would not 
otherwise be considered candidates for BCG. 
 
5.2.4 
Contraindications to receiving intravesical BCG 
BCG is contraindicated in:  
• 
Patients who are pregnant or lactating 
• 
Patients with active tuberculosis 
• 
Immunosuppressed patients with congenital or acquired immune deficiency, 
whether due to concurrent disease (e.g. AIDS, Lymphoma, Leukemia), concomitant 
cancer therapy (cytotoxic drugs, radiation), or immunosuppressive therapy (e.g. 
corticosteroids, DMARDs).  
• 
Symptomatic urinary tract infection 
• 
Febrile illness 
• 
Patients requiring chronic treatment with certain antibiotics that may interfere 
with the effectiveness of BCG. 
• 
Any previous allergies or severe reactions to BCG 
5.2.5 
Contraindications to Accupuncture/Electrostimulation 
 
• 
Not pregnant or trying to become pregnant. Acupunture points included in the protocol are 
contraindicated with pregnancy. 
• 
Does not have a pacemaker. There is potential of electrostimulaton interfering with the 
operation and function of pacemakers. 
5.2.6 
Address concomitant medications which may have an effect on the pharmacokinetics of 
the investigational agent. 
• 
Patients requiring chronic treatment with certain antibiotics that may interfere 
with the effectiveness of BCG. Fluoroquinolone therapy may decrease the efficacy 
of intravesical BCG. Antibiotic therapy for ongoing treatment of active tuberculosis 
will decrease the efficacy of intravesical BCG. 
5.2.7 
Uncontrolled or concurrent illness including, but not limited to, ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac 
arrhythmia, or psychiatric illness/social situations that would limit compliance with study 
requirements. 
 
5.2.8 
Address excluding pregnant women from the study. 
1) Pregnant women are excluded. Acupunture points included in the protocol are contraindicated 
with pregnancy and BCG is contraindicated in pregnancy. 

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5.2.9 
Any additional exclusion criteria and the rationale. 
2) Pacemaker. Patients with pacemakers are restricted due to the potential of electrostimulaton 
interfering with a pacemakers operation. 
3) Platelets: < 20,000/ μL. Risk of bleeding with acupuncture 
4) ANC: < 500 cells/μL. Risk of infection with acupuncture 
5) Received acupuncture in the previous 3 months. Acupuncture treatment effects persist after a 
course of treatment, previous exposure to the intervention has the potential to affect the 
baseline data for treatment and control arms.(25) 
 
 
6.0 
SUBJECT REGISTRATION 
 
Subjects will be registered by the Fred Hutch/UW Study Coordinator and entered into the OnCore CTMS. A complete, 
signed, study consent and HIPAA consent are required for registration. 
 
 
 
7.0 
TREATMENT PLAN 
 
Briefly outline the major treatment components of this protocol including treatment agents, timing and method of 
administration, setting of administration (inpatient or outpatient), duration of therapy and anticipated toxicities and the 
method of treatment of these toxicities. Also address the administration of prophylactic or supportive care drugs or 
regimens and any interactions with the study agent that prohibit the administration of specific concomitant medications. 
 
For those evaluations or procedures that are somewhat flexible in reference to timing, allow for flexibility by stating in the 
protocol that they may be done “plus or minus” x days.  This will further ensure compliance with the protocol. 
 
Outline Treatment Schedule 
Day 
Treatment 
1 +/- 7 
Acupuncture Treatment #1 
BCG Instillation #1 
8 +/- 7 
Acupuncture Treatment #2 
BCG Instillation #3 
15 +/- 7 
Acupuncture Treatment #3 
BCG Instillation #3 
22 +/- 7 
Acupuncture Treatment #4 
BCG Instillation #4 
29 +/- 7 
Acupuncture Treatment #5 
BCG Instillation #5 
36 +/- 7 
Acupuncture Treatment #6 
BCG Instillation #6 
 
 
7.1 Treatment Plan Overview 
 
 
SCHEMA 

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7.2 Waitlist Control  
At the end of the study, participants randomized to the waitlist control group will receive 4 coupons to receive free 
acupuncture in the Prevention Center at the Fred Hutchinson Cancer Research Center. 
 
7.3 Concomitant Medication, Interruption of Therapy, and Supportive Care Guidelines 
• 
A urine analysis will be performed prior to instillation. If bactiuria is present on high power field or >5 WBCs are 
present on high power field and/or gross hematuria is noted and/or the patient complains of acute cystitis 
symptoms (urinary urgency, frequency, dysuria), instillation is deferred and urine is sent for culture to confirm the 
presence of UTI and sensitivity to culture. Appropriate antibiotic therapy is prescribed per standard of care clinical 
practice. Findings are discussed with the prescribing clinician. Microscopic hematuria only or isolated WBCs in an 
otherwise asymptomatic patient do not preclude treatment.  
• 
For patients complaining of bladder spasms, urinary urgency, or frequency: anticholinergic medications such as 
oxybutynin, tolterodine, darifenacin, solifenacin, trospium, fesoterodine or Beta-3 adrenergic agonists such as 
mirabegron will be prescribed. For severe refractory bladder spasms, other medications such as benzodiazepines, 
may be used to relax the bladder.  
• 
For male patients complaining of obstructive urinary symptoms: alpha-antagonists such as tamsulosin may be 
used.  
• 
For patients complaining of bladder pain, local analgesics such as phenazopyridine may be used. Additionally, 
narcotic medications such as oxycodone if necessary, nonnarcotic medications such as Tylenol and non-steroidal 
anti-inflamatory medications) as indicated. 
• 
Patients with fevers, chills, nausea, vomiting, or other systemic symptoms will be directed to their local 
emergency room, urgent care, urologist’s office, or primary care physician as appropriate for further evaluation 
and management.       
 

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7.4 Duration of Therapy 
Therapy is administered weekly for a total of 6 weeks. If a patient’s therapy is deferred for one week due to 
infection, gross hematuria, symptoms, or other reasons (e.g. travel, personal reasons why a patient may not attend 
a scheduled clinic visit, travel issues), patients will resume therapy the next week they are able to do so.  
 
7.5 Duration of Follow-Up 
For the purposes of this study, symptom and adverse event evaluation as well as patient-reported outcomes will 
be collected weekly, including 1 week following completion of BCG therapy. From a bladder cancer standpoint, 
patients are followed on an ongoing basis, and will generally undergo a subsequent cystoscopy in clinic or the OR 
for the purpose bladder cancer surveillance within 2-6 weeks of completion of induction BCG to assess efficacy of 
the treatment and for bladder cancer response vs. persistence and/or progression. No imaging is indicated as per 
this protocol. However, patients with high risk NMIBC undergo annual CT scans for routine standard of care cancer 
staging.  
 
7.6 Dosing Delays/Dose Modifications 
• 
A urine analysis will be performed prior to instillation. If bactiuria is present on high power field or >5 WBCs are 
present on high power field and/or gross hematuria is noted and/or the patient complains of acute cystitis 
symptoms (urinary urgency, frequency, dysuria), instillation is deferred and urine is sent for culture to confirm the 
presence of UTI and sensitivity to culture. Appropriate antibiotic therapy is prescribed per standard of care clinical 
practice. Findings are discussed with the prescribing clinician. Microscopic hematuria only or isolated WBCs in an 
otherwise asymptomatic patient do not preclude treatment.  
• 
For patients reporting severe bladder pain, bladder spasms, urgency/frequency, in consultation with their primary 
urologist, the dose of BCG may be decreased to half-strength (25mg/50mL) as indicated.  
 
 
7.7 End of Treatment (EOT) Visit Schedule and Procedures 
EOT Visits for all subjects who discontinue from the study will occur at least 7 days, but ≤ 30 days, after the last dose of 
intravesical therapy and prior to beginning other treatment. Procedures to be performed during the EOT Visit include: 
• 
Physical Exam 
• 
Vital Signs 
• 
Performance Status 
• 
Labs:  urine analysis with reflex culture 
• 
AE Assessment 
• 
Patient Surveys: EORTC-QLQ-NMIBC-24, EORTC QLQ-C30 
• 
Medication List 
• 
List of complementary and alternative therapies 
 
 
 
8.0 
SUBJECT EVALUATION 
 
8.1 On-Study Clinical Evaluations 
 
Week  
Visit Purpose 
Procedures/Evaluations 
0 
Enrollment 
Registration, Collection of Baseline Demographic and Clinical Data, Performance 
Status, Details regarding the patient’s pathology.  
-- 
Randomization 
Patient will be randomized to either Arm A (Acupuncture) or Arm B (Waitlist Control) 
1 +/-7 
 BCG Treatment 1 
Patient will receive BCG instillation #1 with/without acupuncture intervention prior 
as per their study arm assignment 
Review of Medication List 
Urinanalysis 
Vital signs to include BP, pulse, temperature 

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Assessment of ability to retain intravesical instillation for the desired dwell time (1-2 
hours). Anticholinergic medications may be prescribed per clinic protocol if the 
patient complains of bladder spasms 
Brief physical exam: perineal and abdominal inspection and pain assessment 
(bladder, back, pelvis) before, during, and after instillation) 
Completely drain the bladder prior to instillation of medication for maximum 
medication concentration in the bladder.  
 
Assessments as per the schedule in Section 3.3 
EORTC-QLQ-NMIBC-24 
EORTC-QLQ-C30 
Medication journal 
Assessment of complementary, alternative, and integrative therapies for the prior 3 
months 
Acupuncture Expectency and Treatment Preference Questionnaire  
2 +/-7 
BCG Treatment 2 
Patient will receive BCG instillation #2 with/without acupuncture intervention as per 
their study arm assignment 
Review of Medication List 
Urinanalysis 
Vital signs to include BP, pulse, temperature 
Assessment of ability to retain intravesical instillation for the desired dwell time (1-2 
hours). Anticholinergic medications may be prescribed per clinic protocol if the 
patient complains of bladder spasms 
Brief physical exam: perineal and abdominal inspection and pain assessment 
(bladder, back, pelvis) before, during, and after instillation) 
Completely drain the bladder prior to instillation of medication for maximum 
medication concentration in the bladder.  
 
Assessments as per the schedule in Section 3.3 
EORTC- QLQ-NMIBC-24 
EORTC-QLQ-C30 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the 
prior week 
Medication journal  
3 +/- 7 
BCG Treatment 3 
Patient will receive BCG instillation #3 with/without acupuncture intervention as per 
their study arm assignment 
Review of Medication List 
Urinanalysis 
Vital signs to include BP, pulse, temperature 
Assessment of ability to retain intravesical instillation for the desired dwell time (1-2 
hours). Anticholinergic medications may be prescribed per clinic protocol if the 
patient complains of bladder spasms 
Brief physical exam: perineal and abdominal inspection and pain assessment 
(bladder, back, pelvis) before, during, and after instillation) 
Completely drain the bladder prior to instillation of medication for maximum 
medication concentration in the bladder.  
 
Assessments as per the schedule in Section 3.3 
EORTC-QLQ-NMIBC-24 
EORTC-QLQ-C30 
 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the 
prior week 
Medication journal  
4 +/- 7 
BCG Treatment 4 
Patient will receive BCG instillation #4 with/without acupuncture intervention as per 
their study arm assignment 

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Review of Medication List 
Urinanalysis 
Vital signs to include BP, pulse, temperature 
Assessment of ability to retain intravesical instillation for the desired dwell time (1-2 
hours). Anticholinergic medications may be prescribed per clinic protocol if the 
patient complains of bladder spasms 
Brief physical exam: perineal and abdominal inspection and pain assessment 
(bladder, back, pelvis) before, during, and after instillation) 
Completely drain the bladder prior to instillation of medication for maximum 
medication concentration in the bladder.  
 
Assessments as per the schedule in Section 3.3 
EORTC- QLQ-NMIBC-24 
EORTC-QLQ-C30 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the 
prior week 
Medication journal 
5 +/- 7 
BCG Treatment 5 
Patient will receive BCG instillation #5 with/without acupuncture intervention as per 
their study arm assignment 
Review of Medication List 
Urinanalysis 
Vital signs to include BP, pulse, temperature 
Assessment of ability to retain intravesical instillation for the desired dwell time (1-2 
hours). Anticholinergic medications may be prescribed per clinic protocol if the 
patient complains of bladder spasms 
Brief physical exam: perineal and abdominal inspection and pain assessment 
(bladder, back, pelvis) before, during, and after instillation) 
Completely drain the bladder prior to instillation of medication for maximum 
medication concentration in the bladder.  
 
Assessments as per the schedule in Section 3.3 
EORTC- QLQ-NMIBC-24 
EORTC-QLQ-C30 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the 
prior week 
Medication journal  
6 +/- 7 
BCG Treatment 6 
Patient will receive BCG instillation #6 with/without acupuncture intervention as per 
their study arm assignment 
Review of Medication List 
Urinanalysis 
Vital signs to include BP, pulse, temperature 
Assessment of ability to retain intravesical instillation for the desired dwell time (1-2 
hours). Anticholinergic medications may be prescribed per clinic protocol if the 
patient complains of bladder spasms 
Brief physical exam: perineal and abdominal inspection and pain assessment 
(bladder, back, pelvis) before, during, and after instillation) 
Completely drain the bladder prior to instillation of medication for maximum 
medication concentration in the bladder.  
 
Assessments as per the schedule in Section 3.3 
EORTC- QLQ-NMIBC-24 
EORTC-QLQ-C30 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the 
prior week 
Medication journal 
7 +/- 14 
Follow-up 
Review of Medication List 

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Vital signs to include BP, pulse, temperature 
Physical exam 
Performance Status 
EORTC- QLQ-NMIBC-24 
EORTC-QLQ-C30 
CTCAE v.50 assessment of Systemic Therapy Toxicity assessing symptoms over the 
prior week 
Medication journal 
Follow-up assessment of complementary, alternative, and integrative therapies 
Exit Questionnaire 
 
 
9.0 
SUBJECT DISCONTINUATION OF ACTIVE TREATMENT 
 
Subjects may be removed from this study at any time at their discretion. Subjects may also be removed from this protocol 
if they develop any untoward side effects from the study treatment (acupuncture).  
If a subject withdraws consent to participate in the study or aspects of the study, we will request permission to record 
survival data up to the protocol-described end of the subject follow-up period.. Documentation in the medical record should 
state that the subject is withdrawing from the study and what, if any, selected data the subject will permit the investigator 
to obtain. 
If a subject withdraws from the study, they will not be replaced. Patients who with-draw or whom are removed from the 
study by their primary urologist (e.g. in whom their primary urologist determines it is not safe or indicated to proceed with 
BCG induction due to side effects, other comorbidities, lack of tolerance, or other patient-related concerns) will be surveyed 
to determine the reason for withdrawal.  I.e. An explanation for discontinuing treatment is recorded for each subject 
discontinuing treatment on the appropriate CRF/eCRF. All subjects, irrespective of treatment status, will continue to be 
followed for survival. Treatment in this study must be discontinued for any of the following reasons: 
• 
if the Sponsor decides to stop the study; 
• 
at Investigator’s discretion; 
• 
at the subject’s request; 
• 
if the subject enrolls in a trial of another investigational agent; 
• 
Grade 4 or life-threatening toxicity (See Section 11, Adverse Events) attributable to acupuncture; 
• 
toxicity reactions of Grade 3 or higher, according to the grading in Appendix X - NAME Grading Scale 
• 
pregnancy; 
• 
development of severe BCG toxicity or side effects, e.g. BCG-sepsis, severe refractory BCG cystitis, that preclude 
the patient from being able to tolerate further BCG instillation.  
 
10.0 CONCOMITANT MEDICATIONS 
Patients will have their medication list reviewed and documented in CRF at study entry. On a weekly basis, medication lists 
will be reevaluated for modifications/changes in presecription. Patients will also be requested to fill out a medication diary 
regarding the medications taken over the prior week for management of bladder symptoms including urinary urgency, 
frequency, dysuria, bladder pain, or systemic symptoms such as myalgias, fevers, chills, nausea, vomiting.  
Patients may continue to take all of their routine medications:  
 
• 
Subjects may take doses of nonprescription strength NSAIDS, acetaminophen (paracetamol), ibuprofen or 
acetylsalicylic acid (aspirin) for non-chronic headache, muscle pain, trauma or prophylaxis as long the dosing 
regimens comply with the recommended dose in the product labeling. 
• 
Subjects may receive antihistamine therapy for colds or allergies at non-prescription doses. 
• 
Subjects may take vitamin supplements within a dose range not associated with toxicity. 
• 
Other treatments and medications that may affect immune function, that have known or suspected anti-tumor 
activity, or that could interfere with the imaging assessment of disease progression are not allowed for subjects 
including any and all chemotherapeutics.  

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• 
The use of other investigational agents is not permitted. 
• 
Active immunotherapy is not allowed for any subject. 
• 
Any antibiotic therapy or antimicrobial therapy will be disclosed at the start of each visit. Patients may take 
antimicrobial therapy as indicated for active infection.  
 
 
11.0 ADVERSE EVENTS 
 
11.1 Adverse Event  
 
According to ICH guidelines (Federal Register. 1997; 62(90):25691-25709) and 21 CFR 312.32, IND Safety Reports, and ICH 
E2A, Definitions and Standards for Expedited Reporting, an adverse event is defined as follows: 
 
An adverse event is any untoward medical occurrence in a clinical investigation subject administered a medicinal product 
and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the medicinal product. 
 
Abnormal laboratory values for laboratory parameters specified in the study should not be recorded as an adverse event 
unless an intervention is required (repeat testing to confirm the abnormality is not considered intervention), the laboratory 
abnormality results in a serious adverse event or the adverse event results in study termination or 
interruption/discontinuation of study treatment. 
 
Medical conditions present at screening (i.e., before the study treatment is administered) are not adverse events and 
should not be recorded on adverse event pages of the CRFs.  These medical conditions should be adequately documented 
on the subject chart.  However, medical conditions present at baseline that worsen in intensity or frequency during the 
treatment or post-treatment periods should be reported and recorded as adverse events. 
  
11.2 Serious Adverse Event  
An adverse event should be classified as an SAE if it meets one of the following criteria: 
 
Fatal 
Adverse event results in death. 
Life threatening:  
The adverse events placed the subject at immediate risk of death. This classification 
did not apply to an adverse event that hypothetically might cause death if it were 
more severe.  
Hospitalization:  
It required or prolonged inpatient hospitalization. Hospitalizations for elective 
medical or surgical procedures or treatments planned before enrollment in the 
treatment plan or routine check-ups are not SAEs by this criterion. Admission to a 
palliative unit or hospice care facility is not considered to be a hospitalization.  
Disabling/incapacitating  
Resulted in a substantial and permanent disruption of the subject’s ability to carry 
out normal life functions.  
Congenital anomaly or birth 
defect:  
An adverse outcome in a child or fetus of a subject exposed to the molecule or 
treatment plan regimen before conception or during pregnancy.  
Medically significant:  
The adverse event did not meet any of the above criteria, but could have 
jeopardized the subject and might have required medical or surgical intervention to 
prevent one of the outcomes listed above.  
 
11.3 Unexpected Adverse Event 
An unexpected adverse event is defined as an event that has a nature or severity, or frequency that is not consistent with 
the applicable investigator brochure, or the prior medical condition of the subject or other treatment given to the subject.  
“Unexpected,” as used in this definition, refers to an adverse drug experience that has not been previously observed and 

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reported in preclinical or clinical studies rather than an experience that has not been anticipated based on the 
pharmacological properties of the study drug. 
 
11.4 Monitoring and Recording Adverse Events 
All AEs will be assessed by the investigator or qualified designee and recorded in the CRFs. The investigator should attempt 
to establish a diagnosis of the event on the basis of signs, symptoms and/or other clinical information. In such cases, the 
diagnosis should be documented as the adverse event and/or serious adverse event and not described as the individual 
signs or symptoms. The following information should be recorded: 
• 
Description of the adverse event using concise medical terminology 
• 
Description as to whether or not the adverse event is serious, noting all criteria that apply  
• 
The start date (date of adverse event onset) 
• 
The stop date (date of adverse event resolution) 
• 
The severity (grade) of the adverse event  
• 
A description of the potential relatedness of the adverse event to study drug, a study procedure, or other causality  
• 
The action taken due to the adverse event 
• 
The outcome of the adverse event 
 
11.5 Grading Adverse Event Severity 
All AEs will be graded in severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 
5.0. If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: Grade 1 (mild), Grade 2 
(moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal) to describe the maximum intensity of the 
adverse event.  
 
11.6 Attribution of an Adverse Event 
Association or relatedness to the study agent will be assessed by the investigator as follows: 
• 
Definite: The event follows a reasonable temporal sequence from exposure to the investigational agent, has been 
previously described in association with the investigational agent, and cannot reasonably be attributed to other 
factors such as the subject’s clinical state, other therapeutic interventions or concomitant medications; AND the 
event disappears or improves with withdrawal of the investigational agent and/or re-appears on re-exposure (e.g., 
in the event of an infusion reaction). 
• 
Probable: The event follows a reasonable temporal sequence from exposure to the investigational agent and has 
been previously been described in association with the investigational agent OR cannot reasonably be attributed 
to other factors such as the subject’s clinical state, other therapeutic interventions or concomitant medications. 
• 
Possible: The event follows a reasonable temporal sequence from exposure to the investigational agent, but could 
be attributable to other factors such as the subject’s clinical state, other therapeutic interventions or concomitant 
medications. 
• 
Unlikely: Toxicity is doubtfully related to the investigational agent(s).  The event may be attributable to other 
factors such as the subject’s clinical state, other therapeutic interventions or concomitant medications. 
• 
Unrelated: The event is clearly related to other factors such as the subject’s clinical state, other therapeutic 
interventions or concomitant medications. 
 
For general AE assessment, an AE is considered related if it is assessed as definitely, probably, or possibly related; unrelated 
if it is assessed as unlikely related or unrelated.  
 
11.7 Adverse Event Recording Period 
AEs will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to 
acupuncture.   
 
11.8 Adverse Event Reporting Requirements  
11.8.1 Reporting to IRB 
The investigator will report events to the FHCRC IRB in accordance with the policies of the IRB. 
 
 

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12.0 DATA AND SAFETY MONITORING PLAN 
 
There will be no external monitoring conducted for this study, given the low risk nature of this trial, minimal risk to 
participants and single institution nature of the study.  The trial will be reviewed at least annually and as needed by the 
Consortium Data and Safety Monitoring Committee. 
 
13.0 DATA MANAGEMENT/CONFIDENTIALITY 
 
 
The investigator will ensure that data collected conform to all established guidelines. Each subject is assigned a unique 
subject number to protect subject confidentiality. Subjects will not be referred to by this number, by name, or by any other 
individual identifier in any publication or external presentation. The licensed medical records department, affiliated with 
the institution where the subject receives medical care, maintains all original inpatient and outpatient chart documents. 
 
Subject research files are stored in a secure place, locked in the Research Coordinator’s office for Urologic Oncology within 
the Urology Clinic at UWMC.  Electronic records will be maintained in a HIPAA compliant, password-protected RedCAP 
database maintained by the study PI and research coordinator. Access is restricted to authorized personnel. Records will 
not be shared with any external personnel.  
 
 
14.0 STATISTICAL CONSIDERATIONS 
14.1 Study Design  
This is a pilot randomized control trial.  Patients who provide consent will be randomized 2:1 to receive weekly acupuncture 
pre-BCG treatment plus standard of care symptom management (Arm A) or to the waitlist control arm (Arm B), standard of 
care symptom management plus four coupons for acupuncture after study completion.  
14.2 Primary/Secondary Endpoints/Hypotheses and Analytical Methods 
14.2.1 
Primary Endpoint 
1. Trial recruitment (proportion enrolled versus eligible, reason for not enrolling) will be described 
via qualitative report.  
2. Trial retention (proportion retained versus all enrolled, reason for not completing) will be 
described via qualitative report. Successful retention is defined as continued participation 
within the trial until 1 week following completion of induction BCG.  
3. Protocol adherence (proportion adhered versus all enrolled, specifics for how protocal was not 
followed and why) will be described via qualitative report. Protocol adherence is defined as 
completion of the acupuncture interventions and follow-up surveys if randomized to the 
acupuncture arm or completion of the follow-up surveys if randomized to the control arm. 
4. Clinic staff’s responses to surveys assessing the healthcare burden of this protocol and time 
spent undergoing the acupuncture therapy for the experimental arm will be described via 
qualitative report. 
5. Adverse events associated with acupuncture therapy in the experimental arm will be 
described via qualitative report. 
14.2.2 
Secondary Endpoints  
1. BCG instillation adherence out of a possible planned six treatments (successful adherance 
defined as the number of successfully administered BCG instillations (of a possible 6 total)), 
treatment interruptions (defined as number of weeks that a BCG instillation was delayed) , 
weeks missed (measured as any vs none, and total weeks that BCG was not administered of the 
planned 6 weekly induction doses of intravesical BCG), intravesical BCG dwell times (measured 

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in minutes), and requirement for dose reductions (measured as yes/no) between the 
acupuncture and control arms will be compared via t-test and chi-square as appropriate. 
2. Responses of patients in the experimental and control arms to the EORTC QLQ-NMIBC-24(1) 
and EORTC QLQ-C30(2) symptom index will be compared via t-test at each time point.     
3. Median weekly pill counts of medications prescribed for the management of BCG-related side 
effects, standardized by dosage across medication types, will be compared via Wilcoxen rank 
sum test.   
14.3 Sample Size and Power 
This study will have a sample size of 45 with 2:1 for treatment to control arm. The primary outcome is feasibility. This 
outcome is assessed through a mix of qualitative reports (trial recruitment, retention, protocol adherence, patient/provider 
feedback and evaluation of adverse events). For the qualitative reports there is no statistical testing, thus there is no formal 
power analysis. Based on prior experience we felt we needed at least 15 patients in each arm are to assess these factors 
quantitatively. For the patient survey, the two arms will be compared using t-test. For a trial designed with 90% power and 
two-sided 5% significance, we did the recommended pilot trial sample sizes per treatment arm of 15 for small standardized 
effect sizes (0.2) with continuous data(26). This sample size should also apply to continuous secondary endpoints. 
Extrapolating this reference point, we then doubled the treatment arm size in order assess some of the secondary 
endpoints within the treatment arm (e.g. responses of patients to the EORTC- QLQ-NMIBC-24 symptom index). Lastly, for a 
two-sample proportions test at 80% power and 5% significance, we calculated being able to observe a 0.4 difference 
between the 2 groups for binomial endpoints.  
 
 
14.4 Analysis of Covariates 
As this is a pilot study we do not have adequate power to adjust for covaraites such as age, gender, and existing 
comorbidities. 
14.5 Ethnic and Gender Distribution Chart 
Projected Target Accrual 
ETHNIC AND GENDER DISTRIBUTION CHART 
 
TARGETED / PLANNED ENROLLMENT: Number of Subjects = 45 
Ethnic Category 
 
Sex / Gender 
 
Females 
Males 
Total 
Hispanic or Latino 
1 
2 
3 
Not Hispanic or Latino 
9 
33 
42 
Ethnic Category Total of All Subjects* 
10 
35 
45 
 
Racial Categories 
 
 
American Indian / Alaska Native 
1 
3 
4 
Asian 
1 
3 
4 
Native Hawaiian or Other Pacific Islander 
1 
1 
2 
Black or African American 
1 
1 
2 
White 
6 
27 
33 
More Than One Race 
0 
0 
0 
Racial Categories: Total of All Subjects* 
10 
35 
45 
 

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14.6 Indications for Stopping 
Patients participation will be terminated for the following indications:  
- 
If they express a preference to no longer part in the study/personal preference.  
- 
For major side effects or toxicities or complications associated with acupuncture resulting in patient request to not 
continue 
- 
If the study investigators determine that it is no longer safe or feasible for a patient to continue to receive BCG or 
acupuncture due to progression of bladder cancer or other comorbid conditions.  
 
15.0 INVESTIGATOR OBLIGATIONS 
The PI is responsible for the conduct of the clinical trial at the site and is responsible for personally overseeing the 
treatment of all study subjects. The PI must assure that all study site personnel, including sub-Investigators and other study 
staff members, adhere to the study protocol and to all applicable regulations and guidelines regarding clinical trials both 
during and after study completion. 
 
All subjects are informed of the nature of the program, its possible hazards, and their right to withdraw at any time, and 
each subject signs a form indicating their consent to participate prior to receiving any study-related procedures (see 
Appendices 1). 
 
 
 
 

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16.0 REFERENCES 
 
1. 
Blazeby JM, Hall E, Aaronson NK, Lloyd L, Waters R, Kelly JD, et al. Validation and reliability testing of the EORTC 
QLQ-NMIBC24 questionnaire module to assess patient-reported outcomes in non-muscle-invasive bladder cancer. Eur Urol. 
2014;66(6):1148-56. 
2. 
Fayers P, Bottomley A, Group EQoL, Quality of Life U. Quality of life research within the EORTC-the EORTC QLQ-
C30. European Organisation for Research and Treatment of Cancer. European journal of cancer. 2002;38 Suppl 4:S125-33. 
3. 
Chang SS, Boorjian SA, Chou R, Clark PE, Daneshmand S, Konety BR, et al. Diagnosis and Treatment of Non-Muscle 
Invasive Bladder Cancer: AUA/SUO Guideline. J Urol. 2016;196(4):1021-9. 
4. 
American Cancer Society. Key Statistics for Bladder Cancer 2019 [Available from: 
https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html. 
5. 
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology - Bladder Cancer Version 
4.2019 2019 [Available from: https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf  
6. 
Joshua JM, Vijayan M, Pooleri GK. A retrospective analysis of patients treated with intravesical BCG for high-risk 
nonmuscle invasive bladder cancer. Ther Adv Urol. 2019;11:1756287219833056. 
7. 
Nummi A, Jarvinen R, Sairanen J, Huotari K. A retrospective study on tolerability and complications of bacillus 
Calmette-Guerin (BCG) instillations for non-muscle-invasive bladder cancer. Scand J Urol. 2019;53(2-3):116-22. 
8. 
Colombel M, Saint F, Chopin D, Malavaud B, Nicolas L, Rischmann P. The effect of ofloxacin on bacillus calmette-
guerin induced toxicity in patients with superficial bladder cancer: results of a randomized, prospective, double-blind, 
placebo controlled, multicenter study. J Urol. 2006;176(3):935-9. 
9. 
Forde JC, Jaffe E, Stone BV, Te AE, Espinosa G, Chughtai B. The role of acupuncture in managing overactive bladder; 
a review of the literature. International urogynecology journal. 2016;27(11):1645-51. 
10. 
Zhao Y, Zhou J, Mo Q, Wang Y, Yu J, Liu Z. Acupuncture for adults with overactive bladder: A systematic review and 
meta-analysis of randomized controlled trials. Medicine. 2018;97(8):e9838. 
11. 
Mak TC, Cho WC, Chen HY. Acupuncture for overactive bladder in adults: a systematic review and meta-analysis. 
Acupunct Med. 2019:acupmed2017011528. 
12. 
de Wall LL, Heesakkers JP. Effectiveness of percutaneous tibial nerve stimulation in the treatment of overactive 
bladder syndrome. Res Rep Urol. 2017;9:145-57. 
13. 
Lao L. Acupuncture practice, past and present: is it safe and effective? Journal of the Society for Integrative 
Oncology. 2006;4(1):13-5. 
14. 
Garcia MK, Driver L, Haddad R, Lee R, Palmer JL, Wei Q, et al. Acupuncture for treatment of uncontrolled pain in 
cancer patients: a pragmatic pilot study. Integrative cancer therapies. 2014;13(2):133-40. 
15. 
Qin Q, Mo Q, Liu K, He X, Gao X, Zhu B. Acupuncture at homotopic acupoints exerts dual effects on bladder motility 
in anesthetized rats. BMC Complement Altern Med. 2015;15:267. 
16. 
Mak TC, Chen HY, Cho WC. Acupuncture for overactive bladder in adults: a systematic review and meta-analysis. 
Acupuncture in medicine : journal of the British Medical Acupuncture Society. 2019;37(6):321-31. 
17. 
MacPherson H, Altman DG, Hammerschlag R, Youping L, Taixiang W, White A, et al. Revised STandards for 
Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): Extending the CONSORT statement. Journal of evidence-
based medicine. 2010;3(3):140-55. 
18. 
Witt CM, Pach D, Brinkhaus B, Wruck K, Tag B, Mank S, et al. Safety of acupuncture: results of a prospective 
observational study with 229,230 patients and introduction of a medical information and consent form. Forschende 
Komplementarmedizin. 2009;16(2):91-7. 
19. 
Deadman P, Al-Khafaji M, Baker K. A Manual of Acupuncture. 1998:256-325. 
20. 
National Acupuncture Foundation. Clean Needle Technique Manual for Acupuncturists: Guidelines and Standards 
for the Clean and Safe Clinical Practice of Acupuncture. 2003. 
21. 
Seirin. Manufacturing 2019 [Available from: http://seirinamerica.com/spinex/. 
22. 
Pantheon Research. Why Pantheon http://pantheonresearch.com/why-pantheon/ [ 
23. 
ITO Physiotherapy & Rehabilitation. Global Company http://www.itocoltd.com [ 
24. 
Tens Plus Industrial Company. About Us. http://www.tensplus.com/aboutus.asp. 
25. 
MacPherson H, Vertosick EA, Foster NE, Lewith G, Linde K, Sherman KJ, et al. The persistence of the effects of 
acupuncture after a course of treatment: a meta-analysis of patients with chronic pain. Pain. 2017;158(5):784-93. 
26. 
Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to 
minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat Methods 
Med Res. 2016;25(3):1057-73. 
 

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17.0 APPENDICES 
 
 
Appendix A: 
Sample Schema 
 
Appendix B: 
ECOG Performance Status Scale 
 
Appendix C: 
Acupoint Location Diagram 
 
Appendix D: 
Study Calendar 
 
 

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APPENDIX A – Study Schema 
 
 
 

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APPENDIX B – ECOG Performance Status Scale 
 
ECOG Performance Status Scale 
 
GRADE 
SCALE 
0 
Fully active, able to carry out all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work 
2 
Ambulatory and capable of all self-care but unable to carry out work activities. Up and about more than 50% of waking hours.  
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.  
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
5 
Dead 
 
 
 

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APPENDIX C: Acupoint Location Diagram 

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APPENDIX D: STUDY CALENDAR 
 
Study Calendar 
 
Screening 
Baseline data 
 
Week 1 
BCG 1 
 
Week 2 
BCG 2 
 
Week 3 
BCG 3 
 
Week 4 
BCG 4 
 
Week 5 
BCG 5 
 
Week 6 
BCG 6 
Week 7 
Follow Up 
Procedure 
within X days 
1 week prior to BCG #1 
+/- X Days 
Day 1 
+/- 7 Days 
+/- 7 Days 
+/- 7 Days 
+/- 7 Days 
+/- 7 Days 
+/- 7 Days 
Physical Exam 
X 
 
X 
X 
X 
X 
X 
X 
X 
Medical History 
Clinicopathologic  
 
X 
 
 
 
 
 
 
 
Demographic Data 
 
X 
 
 
 
 
 
 
 
Current Use of CAM/IM 
 
X 
 
 
 
 
 
 
 
Informed Consent 
 
X 
 
 
 
 
 
 
 
ECOG 
X 
 
 
 
 
 
 
 
X 
EORTC-QLQ-NMIBC-24 
 
 
X 
X 
X 
X 
X 
X 
X 
EORTC-QLQ-C30 
 
 
X 
X 
X 
X 
X 
X 
X 
CTCAE v5 
 
 
 
X 
X 
X 
X 
X 
X 
Assessment of CAM/IM Use 
 
X 
X 
X 
X 
X 
X 
X 
X 
Medication Journal 
 
 
X 
X 
X 
X 
X 
X 
X 
AE to Study Intervention 
 
 
 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
 
X 
X 
X 
X 
X 
X 
X 
UA 
 
 
X 
X 
X 
X 
X 
X 
 
Study Intervention Therapy 
 
 
X 
X 
X 
X 
X 
X 
 
Foley Cath bladder emptied 
 
 
X 
X 
X 
X 
X 
X 
 
BCG 
 
 
X 
X 
X 
X 
X 
X 
 
Bladder Void Time recorded 
 
 
X 
X 
X 
X 
X 
X