Single-arm, Phase II Study Evaluating the Clinical Impact of Navigation on Delays and Racial Disparities Starting Postoperative Radiation Therapy for Adults With Locally Advanced Head and Neck Cancer: The NDURE Study
Phase: NA
Conditions: Cancer of Head and Neck
Sponsor: Medical University of South Carolina

 
 
 
 
 
 
 
 
 
 
 
 
 
Single-arm, Phase II Study Evaluating the Clinical Impact 
of Navigation on Delays and Racial Disparities Starting 
Postoperative Radiation Therapy for Adults with Locally 
Advanced Head and Neck Cancer: The NDURE Study 
Protocol Number: CTO# 102963 
National Clinical Trial (NCT) Identified Number:  NCT03821064 
Principal Investigator (PI): Evan Graboyes, MD 
Sponsor: Hollings Cancer Center (HCC) 
Grant Title: Improving the Timeliness and Equity of Adjuvant Therapy Following 
Surgery for Head and Neck Cancer 
Grant Number: 2K12 CA157688-6 
Funded by: NCI 
Version Number:  v.3  
31 July 2019

 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by 
the recipient that no unpublished information contained herein will be published or disclosed without 
prior approval of the Principal Investigator or other participating study leadership and as consistent with 
the National Institutes of Health (NIH) terms of award. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL VERSION 3  
Section Number & Title 
Description of Change 
Brief Rationale 
5.1 Inclusion Criteria 
Specified differences in staging 
between 7th and 8th edition of 
AJCC as it relates to HPV-positive 
and HPV-negative HNC 
 
Removal of inclusion criteria 
related to willingness to comply 
with study 
Adjuvant therapy decisions for 
surgically-managed  HPV-related 
HNC are based on 7th edition 
staging 
 
Recommendation of MUSC IRB  
in similar type of trial 
5.2 Exclusion Criteria 
Added specific adverse features 
that are indications for adjuvant 
therapy 
Prevent uncertainty about 
eligibility 
5.4 Screen Failures 
Defined screen failure as subject 
who consents to participate in 
this study but is not 
subsequently assigned to the 
study intervention 
Reflect change to efficacy 
analytic population from ITT to 
modified ITT (with modification 
to address patients who were 
previously described as screen 
failures) 
9.3 Populations for Analyses 
Switched from ITT to modified 
ITT for efficacy analyses 
Facilitate analysis of expected 
patients who enroll into study 
but over time develop exclusion 
criteria (and thus analysis for 
efficacy) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

The NDURE Study Trial Protocol 
 
Version 3 
Protocol 102963 
 
31 July 2019 
 
Table of Contents 
STATEMENT OF COMPLIANCE .............................................................................................................................. 6 
INVESTIGATOR’S SIGNATURE ............................................................................................................................... 7 
1 
PROTOCOL SUMMARY ............................................................................................................................... 8 
1.1 
Synopsis ............................................................................................................................................... 8 
1.2 
Schema ............................................................................................................................................... 11 
1.3 
Schedule of Activities ..................................................................................................................... 12 
2 
INTRODUCTION .......................................................................................................................................... 12 
2.1 
Study Rationale ............................................................................................................................... 12 
2.2 
Background ....................................................................................................................................... 13 
2.3 
Risk/Benefit Assessment ............................................................................................................... 14 
2.3.1 
Known Potential Risks ................................................................................................ 14 
2.3.2 
Known Potential Benefits .......................................................................................... 14 
2.3.3 
Assessment of Potential Risks and Benefits ........................................................ 14 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 15 
4 
STUDY DESIGN ............................................................................................................................................ 16 
4.1 
Overall Design .................................................................................................................................. 16 
4.2 
Scientific Rationale for Study Design ........................................................................................ 16 
4.3 
Justification for Intervention ....................................................................................................... 16 
4.4 
End-of-Study Definition ................................................................................................................. 17 
5 
STUDY POPULATION ................................................................................................................................. 17 
5.1 
Inclusion Criteria ............................................................................................................................. 17 
5.2 
Exclusion Criteria ............................................................................................................................. 17 
5.3 
Lifestyle Considerations ................................................................................................................ 18 
5.4 
Screen Failures ................................................................................................................................. 18 
5.5 
Strategies for Recruitment and Retention ............................................................................... 18 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ............................................. 19 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration ........................ 19 
6.1.1 
Study Intervention or Experimental Manipulation Description ..................... 20 
6.1.2 
Administration and/or Dosing ................................................................................. 21 
6.2 
Fidelity ................................................................................................................................................ 21 
6.2.1 
Interventionist Training and Tracking ................................................................... 21 
6.3 
Measures to Minimize Bias: Randomization and Blinding ................................................. 21 
6.4 
Study Intervention/Experimental Manipulation Adherence .............................................. 21 
6.5 
Concomitant Therapy .................................................................................................................... 21 
6.5.1 
Rescue Therapy ............................................................................................................ 21 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ....................................................................................... 21 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ............................... 21 
7.2 
Participant Discontinuation/Withdrawal from the Study ................................................... 21 
7.3 
Lost to Follow-Up ............................................................................................................................ 22 
8 
STUDY ASSESSMENTS AND PROCEDURES .......................................................................................... 22 
8.1 
Endpoint and Other Non-Safety Assessments ........................................................................ 22 
 

The NDURE Study Trial Protocol 
 
Version 3 
Protocol 102963 
 
31 July 2019 
 
9 
STATISTICAL CONSIDERATIONS ............................................................................................................. 25 
9.1 
Statistical Hypotheses ................................................................................................................... 25 
9.2 
Sample Size Determination .......................................................................................................... 25 
9.3 
Populations for Analyses .............................................................................................................. 26 
9.4 
Statistical Analyses ......................................................................................................................... 27 
9.4.1 
General Approach ....................................................................................................... 27 
9.4.2 
Analysis of the Primary Endpoint(s) ....................................................................... 27 
9.4.3 
Analysis of the Secondary Endpoint(s) .................................................................. 28 
9.4.4 
Safety Analyses ............................................................................................................ 28 
9.4.5 
Baseline Descriptive Statistics ................................................................................. 28 
9.4.6 
Planned Interim Analyses ......................................................................................... 28 
9.4.7 
Sub-Group Analyses .................................................................................................... 29 
9.4.8 
Tabulation of Individual Participant Data ............................................................ 29 
9.4.9 
Exploratory Analyses .................................................................................................. 29 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ................................ 29 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ................................................... 29 
10.1.1 
Informed Consent Process ........................................................................................ 29 
10.1.2 
Study Discontinuation and Closure ........................................................................ 29 
10.1.3 
Confidentiality and Privacy ....................................................................................... 30 
10.1.4 
Future Use of Stored Specimens and Data .......................................................... 30 
10.1.5 
Key Roles and Study Governance ........................................................................... 30 
10.1.6 
Safety Oversight .......................................................................................................... 30 
10.1.7 
Clinical Monitoring ...................................................................................................... 30 
10.1.8 
Quality Assurance and Quality Control ................................................................. 30 
10.1.9 
Data Handling and Record Keeping ....................................................................... 31 
10.1.11 
Publication and Data Sharing Policy ...................................................................... 31 
10.2 
Additional Considerations ............................................................................................................ 32 
10.3 
Abbreviations and Special Terms ............................................................................................... 32 
10.4 
Protocol Amendment History ...................................................................................................... 34 
11 
REFERENCES ................................................................................................................................................ 33 
 

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STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with International Council on Harmonisation Good Clinical Practice (ICH GCP), 
applicable United States (US) Code of Federal Regulations (CFR), and the National Cancer Institute (NCI) Terms and 
Conditions of Award. The Principal Investigator will assure that no deviation from, or changes to the protocol will take 
place without prior agreement from the funding agency and documented approval from the Institutional Review Board 
(IRB), and the Investigational New Drug (IND) or Investigational Device Exemption (IDE) sponsor, if applicable, except 
where necessary to eliminate an immediate hazard(s) to the trial participants. All personnel involved in the conduct of 
this study have completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be submitted to the IRB 
for review and approval. Approval of both the protocol and the consent form(s) must be obtained before any participant 
is consented. Any amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study. All changes to the consent form(s) will be IRB approved; a determination will be made 
regarding whether a new consent needs to be obtained from participants who provided consent, using a previously 
approved consent form. 
 
 

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INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary assurances that this study will 
be conducted according to all stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal regulations and ICH guidelines, as 
described in the Statement of Compliance above. 
 
Principal Investigator: 
 
 
Signed: 
 
Date: 
7/31/19 
 
Name:  Evan Graboyes 
 
Title: Single-arm, Phase II Study Evaluating the Clinical Impact of Navigation on Delays and 
Racial Disparities Starting Postoperative Radiation Therapy for Adults with Locally Advanced 
Head and Neck Cancer: The NDURE Study 
 
Investigator Contact Information 
Affiliation: Medical University of South Carolina 
Address: 135 Rutledge Avenue, MSC 550, Charleston, SC 29425 
Telephone: (843)-792-0719 
Email: graboyes@musc.edu 
 
 
 
 
 
 

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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
 
 
Title: 
Single-arm, Phase II Study Evaluating the Clinical Impact of Navigation 
on Delays and Racial Disparities Starting Postoperative Radiation 
Therapy for Adults with Locally Advanced Head and Neck Cancer: The 
NDURE Study 
 
Grant Number: 
2K12CA157688-6 
 
Study Description: 
 
In this study, we evaluate the feasibility, acceptability, preliminary 
clinical impact, and preliminary behavioral impact of NDURE 
(Navigation for Disparities and Untimely Radiation thErapy), our multi-
level, theory-based navigation intervention to improve timely, 
equitable post-operative radiation treatment (PORT) among Head and 
Neck Cancer (HNC) patients. We hypothesize that NDURE will be 
feasible, acceptable, improve the timeliness of PORT for white and 
African American (AA) HNC patients and decrease disparities in delay 
between the two groups by improving system-, interpersonal-, and 
individual-level health behavior constructs. 
 
Objectives: 
 
Primary Objective: 
1. To evaluate the preliminary clinical impact of NDURE on delays 
starting PORT among white and AA HNC patients. 
 
Secondary Objectives: 
1. To evaluate the preliminary clinical impact of NDURE on racial 
disparities in delays starting PORT among white and AA HNC patients. 
 
2. To compare the rate of PORT delay in NDURE to local and national 
historical controls. 
 
3. To evaluate the preliminary clinical impact of NDURE on barriers and 
cancer care delivery processes. 
 
3. To assess the feasibility of NDURE among white and AA HNC 
patients. 
 
4. To assess the acceptability of NDURE to white and AA HNC patients 
and HNC providers. 
 
5. To evaluate the preliminary behavioral mechanism of action of 
NDURE. 
 

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Endpoints: 
Primary Endpoint: 
Initiation of postoperative PORT > 6 weeks after surgery 
 
Secondary Endpoints: 
Racial disparities in initiation of PORT > 6 weeks after surgery 
Days between surgery and the start of PORT 
 
Barriers resolved 
Unresolved barriers 
Pre-Surgical Radiation Consultation 
Pre-Radiation Therapy Dental Extractions 
Surgery to Pathology Report < 7 days 
Surgery to PORT Referral < 10 days 
RT Referral to Consult  < 10 days 
RT Consult to Initiation < 21 days 
 
NDURE Accrual 
NDURE Completion 
Navigation Session Completion 
Navigator Caseload 
Navigator Time Allocation (Direct) 
Navigator Time Allocation (Indirect) 
 
Patient Satisfaction with the Interpersonal Relationship with the 
Navigator Score 
Patient Satisfaction with Logistical Aspects of Navigation Scale Score 
 
Care Transition Measure-15 (CTM-15) Score 
 Interpersonal Support Evaluation List-12 (ISEL-12) Score 
 Perceived Susceptibility Score 
 Illness Perception Questionnaire-Revised (IPQ-R) Consequences Sub-
Scale Score 
 Perceived Barriers Score 
 Communication & Attitudinal Self-Efficacy Scale (CASE)-Cancer Score 
 
Study Population: 
The study population will consist of patients 18 years of age or older, 
self-identified white or AA race, locally advanced HNC (American Joint 
Committee on Cancer [AJCC] clinical stage III-IV) undergoing curative 
intent surgery at the Medical University of South Carolina (MUSC) 
followed by PORT (at MUSC or non-MUSC). 
Phase or Stage: 
II 
 
Description of 
Sites/Facilities Enrolling 
Participants: 
The study will be conducted, and participants enrolled, at the MUSC 
Hollings Cancer Center (HCC) Head and Neck Tumor Center. The Head 
and Neck Tumor Center is a high-volume, multidisciplinary center 
designed for unsurpassed clinical care and optimized for integration of 
research activities. The Head and Neck Tumor Center is a regional 
center of excellence for HNC clinical care. 
 

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Description of Study 
Intervention/Experimental 
Manipulation: 
NDURE is a theory-based, multi-level patient navigation (PN) 
intervention consisting of three in-person, clinic-based sessions of 
manualized PN with multiple intervention components that target 
system- (care coordination), interpersonal- (social support), and 
individual- (health belief model (HBM); perceived susceptibility, 
severity, barriers, self-efficacy) level health behavior theoretical 
constructs to reduce barriers to care, increase HNC care delivery, and 
improve clinical outcomes (timely, equitable PORT). NDURE will be 
delivered from surgical consultation to PORT initiation (~3 months). 
The three in-person NDURE navigation sessions, which are expected to 
take 30-60 minutes each, will coincide with the presurgical consult, 
hospital discharge, and 1st postoperative clinic visit, time points chosen 
to facilitate case identification and coordination across key care 
transitions. 
 
Study Duration: 
18 months  
 
Participant Duration: 
5 months 
 
 
 

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1.2 
SCHEMA  
Flow Diagram 
 

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1.3 
SCHEDULE OF ACTIVITIES  (SOA) 
 
 
2 
 
INTRODUCTION 
2.1 
STUDY RATIONALE  
HNC is responsible for 14,000 deaths annually in the US and has poor survival (50% at 5 years) despite intense treatment 
including surgery, radiation, and chemotherapy1. HNC is also a disease with significant racial disparities in mortality; AAs 
have a 51% relative decrease in survival compared to whites2. Delays starting PORT after HNC surgery are a key driver of 
high mortality for all HNC patients and racial disparities in survival for AAs. As such, the delivery of timely PORT is an 
appealing therapeutic target to address both issues3,4. We have shown that delayed, non-guideline-adherent PORT 
initiation (> 6 weeks after surgery5) affects 56% of HNC patients6, is 31% more common in AA HNC patients than whites6, 
is associated with an 11% absolute decrease in 5-year survival7, and is a key driver of racial differences in mortality3. Our 
pilot qualitative data suggest that treatment toxicity, travel distance, care coordination, finances, support, knowledge, 
and communication are barriers to timely, equitable PORT. Delivering timely PORT to all HNC patients is critical to 
prevent excess mortality and racial disparities in survival. Unfortunately, effective interventions to decrease delays and 
racial disparities starting PORT are unknown8,9, due in part to the lack of understanding of the relevant barriers in this 
clinical setting. One potential strategy to improve timely, equitable PORT is patient navigation (PN), a barrier-focused 
intervention that improves the timeliness and racial equity of initial cancer care (screening, treatment initiation)10,11. 
However, the impact of PN on delays and racial disparities starting PORT, a different point on the cancer care continuum 
than screening and treatment initiation, is unknown12. In this proposal, we extend our work to develop and evaluate the 
 
Pre-screening 
(Pre-consent) 
 
Visit 1 
 
Visit 2 
 
Visit  3 
 
Visit  4 
 
Visit  5 
 
Electronic Medical Record (EMR) 
Review Eligibility 
X 
 
 
 
 
 
Informed Consent 
 
X 
 
 
 
 
Demographics 
 
X 
 
 
 
 
Clinical and oncologic history 
 
X 
 
 
 
 
Cultural Factors 
 
X 
 
 
 
 
Barrier Load 
 
X 
X 
X 
X 
X 
Symptom Severity 
 
X 
X 
X 
X 
X 
Outcome Evaluation 
 
 
 
 
 
 
Barrier Reduction 
 
 
X 
X 
X 
X 
Unresolved Barriers 
 
 
X 
X 
X 
X 
Satisfaction with Navigation- 
Interpersonal 
 
 
 
 
 
X 
Satisfaction with Navigation- 
Logistical 
 
 
 
 
 
X 
Care Transition 
 
 
 
 
 
X 
Interpersonal Support 
 
X 
 
 
 
X 
Perceived Susceptibility 
 
X 
 
 
 
X 
Perceived Consequences 
 
X 
 
 
 
X 
Perceived Barriers 
 
X 
 
 
 
X 
Perceived Self-Efficacy in Cancer Care 
 
X 
 
 
 
X 

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feasibility, acceptability, and preliminary clinical impact of NDURE, our multi-level, theory-based PN intervention to 
improve timely, equitable PORT among HNC patients. 
 
2.2 
BACKGROUND  
Head and Neck Cancer (HNC) is a Disease with High Mortality and Racial Disparities in Survival. HNC, which affects the 
tongue, pharynx, larynx, and neck, is diagnosed in 65,000 patients in the US annually and causes 14,000 deaths per 
year1. No screening tests exist for HNC, and as a result, more than two-thirds of patients present with locally advanced 
disease1. Despite aggressive multimodal therapy consisting of surgery followed by postoperative radiation therapy 
(PORT) and concurrent chemotherapy5, outcomes remain poor with only 50% of patients with locally-advanced HNC 
surviving 5 years1. HNC is also a disease with significant racial disparities in mortality; African Americans (AAs) with HNC 
have a 19% absolute decrease in 5-year survival relative to white HNC patients13 and a 51% relative decrease in survival2. 
 
Delays Starting PORT Contribute to High Mortality in HNC and Racial Disparities in Survival. Delays in cancer care 
delivery are a key driver of mortality for HNC patients14 and a source of racial disparities in survival for AAs3. The critical 
time period for HNC patients is the time from surgery to the start of PORT8,15, the only aspect of timely HNC care 
incorporated in National Comprehensive Cancer Network Guidelines (< 6 weeks after surgery)5. Delays starting PORT are 
associated with increased recurrence and decreased survival7,16,17. The 11% improved 5-year survival seen with timely 
PORT7 is large, comparable in magnitude to the benefit seen from adding Cisplatin to PORT in landmark HNC trials18,19. 
Unfortunately, delays starting PORT affect 56% of HNC patients6. Delays starting PORT also disproportionately affect 
AAs, who are 31% more likely to experience delays than whites after adjusting for insurance, income, education, and 
stage6. The high rate of delayed PORT among AA HNC patients is a source of preventable mortality and contributes to 
racial disparities in survival7. 
 
The Barriers that Contribute to Delays and Racial Disparities Starting PORT After HNC Surgery are Unknown. AA race, 
insurance status, prolonged travel distance, and care fragmentation are associated with delayed PORT6,20-22. However, 
the barriers to timely care delivery at the patient-, provider-, and system-level remain unknown. As a result, the 
development of targeted, multi-level interventions to address barriers and improve the delivery of timely, equitable 
PORT for HNC patients has been impeded. To prevent continued treatment delays, it is critically important to identify 
the barriers to delivering timely, equitable PORT. 
 
Effective Interventions to Decrease Delays and Racial Disparities Starting PORT are Lacking. The care delivery pathway 
for PORT, which is potentially modifiable through a multi-level intervention, represents an appealing target to decrease 
mortality and racial disparities in survival for HNC patients3,4,8. Unfortunately, despite the large clinical impact of delayed 
PORT on mortality and racial disparities in survival, no effective interventions have been described8,9,23. A prior study 
using an atheoretical, provider-centric approach did not find a decrease in the rate of PORT delay24. Improving the 
timeliness of PORT for white and AA HNC patients is crucial to improving survival for all HNC patients and decreasing 
racial disparities in mortality. 
 
Patient Navigation (PN) is a Promising Strategy to Deliver Timely, Equitable PORT after HNC Surgery. PN is a patient-
centered intervention that addresses barriers to cancer care, thereby improving the delivery of timely, equitable cancer 
screening, decreasing racial differences in post-screening diagnostic resolution, and decreasing care fragmentation10,11,25-
27. However, the efficacy of PN in the sequential multimodal cancer care setting (e.g. surgery then PORT) is unknown12; 
care transitions following surgery involve unique care barriers and care coordination challenges28. To address the lack of 
effective interventions to decrease delays and racial disparities starting PORT after HNC surgery8, we will develop and 
test NDURE (Navigation for Disparities and Untimely Radiation thErapy), our multi-level, theory-based PN intervention to 
improve timely, equitable PORT among HNC patients. The underlying scientific premise is that our NDURE PN 
intervention has the potential to decrease delays starting PORT among HNC patients because PN is most effective in 1) 
populations with low adherence rates10 (timely PORT adherence is < 50% overall and <40% among AAs6); 2) racial 
minority populations10,29 (delays starting PORT are 31% more common in AAs6); and 3) the setting of fragmented care10,27 

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(PORT delivery involves coordinating consults with seven medical specialties23, care transitions from inpatient to 
outpatient, and care transitions across healthcare systems [in 51% of cases6]). 
 
2.3 
RISK/BENEFIT ASSESSMENT  
2.3.1 KNOWN POTENTIAL RISKS  
Overall, this research study poses no more than minimal risks to participants. There are no physical, financial, legal, 
social, or cultural, risks to the study participants by joining this study. There are slight psychological risks, as described 
below. There is a slight risk that subjects may experience adverse psychological reactions such as anxiety or stress as a 
result of discussing issues related to cancer or barriers to cancer care. We believe that this risk is minimal. We are using 
survey items that are commonly used in clinical settings and subjects are likely to have had prior exposure to similar 
types of questions as part of their medical care. Furthermore, in our past studies with white and AA men and women 
with HNC, the overwhelming majority of respondents have said they found the questions that we have asked related to 
care have not been upsetting. 
 
There is also a slight risk that confidential information about the participant may be accidentally disclosed as study 
participants may be asked to provide information considered confidential or private during study interviews. The 
likelihood of this risk is low as all the investigators have been involved in similar research in the past and have not 
experienced this problem before due to adequate safeguards. 
 
The decision to participate in this research will be voluntary and individuals may refuse to take part or choose to stop 
taking part at any time. Participants will also be encouraged to take their time when answering questions and may 
decline to answer any question at any time. If patients become upset talking about their cancer and the barriers that 
they faced, they will be offered a referral to the HCC Behavioral Medicine program (which is covered by most health 
insurance programs) or the HCC Social Worker who will offer links to other HCC and community resources. 
 
2.3.2 KNOWN POTENTIAL BENEFITS  
Extrapolating from data about PN in other settings, NDURE may improve the timeliness of PORT after HNC surgery and 
decrease racial disparities in timely HNC care. However, although we hypothesize a direct benefit to participants in the 
NDURE study (in terms of timely HNC care), it is unknown whether patients will experience a direct benefit. Data 
generated from this study are expected to provide benefits to society by providing new knowledge about a practical and 
scalable strategy for addressing racial disparities in the timeliness of PORT in HNC patients. Because timely PORT is 
associated with decreased rates of recurrence and improved survival, it is expected that if we decrease racial disparities 
in delays starting PORT, we will improve survival and racial equity in outcomes. 
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
The decision to participate in this research will be voluntary. Participants will be informed that they can stop 
participating at any time and/or refrain from answering any questions that make them uncomfortable. The interviewers 
are trained researchers with experience conducting interviews related to cancer. By using survey items that are 
commonly used in clinical settings (to which subjects have likely had prior exposure as part of their medical care) we will 
minimize psychological risk. If a participant has a psychological adverse event (AE) talking about his/her cancer and/or 
the barriers that he/she faced during treatment, the participant will be offered a referral to the HCC Behavioral 
Medicine program (which is covered by most health insurance programs) or the HCC Social Worker who will offer links 
to other HCC and community resources as detailed in the Data and Safety Monitoring Plan. Immediate backup and 
support will be available.  
 
To help ensure and protect privacy of participants and confidentiality of research data for the study, we will assign a 
unique study ID number to each subject’s information in place of his/her name and will label data collection forms with 
the ID number. All hard copy and electronic files will be stored appropriately using double-locked methods and 
password-protection. Only the study team members will have access to study records. Participant data will be collected 

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and recorded on either a password-protected electronic data capture format (REDCap) or paper-based forms depending 
upon patient preference. For the paper collection data method, the data collection form will be labeled only with the 
participant's unique study ID number, and then stored within locked drawers in a locked office. 
 
The information on these paper forms will be transferred to a password-protected REDCap database. Any exported data 
for analysis will be de-identified with all privately identifiable information automatically removed. The key linking subject 
ID number to an individual will be stored in the password protected REDCap database. The audio recordings from the 
qualitative interviews will be labeled only with the patient’s unique study ID and stored using password-protected files 
only accessible by the study team through password-protected servers. Once data have been collected, only de-
identified data will be exported for analysis. All study personnel will participate in training on protecting the privacy of 
study participants and personal information will not be disclosed to anyone outside of the research team. Only the 
principal investigator and study staff participating in data collection or analysis will have access to the data. We have no 
plan to use laptops, jump drives, CDs/DVDs to transport data. 
On the whole, given the minimal risks to the study participants and the potential benefit of the research to participants 
and society, we believe that the potential reward to participants and society substantially outweighs the risks to the 
participants. 
 
 
 
 
3 
OBJECTIVES AND ENDPOINTS  
OBJECTIVES 
ENDPOINTS 
Primary 
 
To evaluate the preliminary clinical impact of NDURE 
on delays starting PORT among white and AA HNC 
patients. 
Initiation of PORT > 6 weeks after surgery  
 
 
Secondary 
 
To evaluate the preliminary clinical impact of NDURE 
on racial disparities in delays starting PORT among 
white and AA HNC patients. 
Initiation of PORT > 6 weeks after surgery 
Days between surgery and the start of PORT 
To compare the rate of PORT delay in NDURE to 
local and national historical controls. 
Initiation of PORT > 6 weeks after surgery 
Days between surgery and the start of PORT 
To evaluate the preliminary clinical impact of NDURE 
on barriers and cancer care delivery processes. 
Barriers resolved 
Unresolved barriers 
Pre-surgical Radiation Consultation 
Pre-RT Dental Extractions 
Surgery to Pathology Report < 7 d 
Surgery to PORT Referral < 10 d 
RT Referral to Consult < 10 d 
RT Consult to Initiation < 21 d 
To assess the feasibility of NDURE among white and 
AA HNC patients. 
NDURE Accrual 
NDURE Completion 
Navigation Session Completion 
Navigator Caseload 
Navigator Time Allocation (Direct) 
Navigator Time Allocation (Indirect) 
To assess the acceptability of NDURE to white and 
AA HNC patients and HNC providers. 
Patient Satisfaction with the Interpersonal 
Relationship with the Navigator Score 
Patient Satisfaction with Logistical Aspects of 
Navigation Scale Score 

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OBJECTIVES 
ENDPOINTS 
To evaluate the preliminary behavioral mechanism 
of action of NDURE 
Care Transition Measure-15 (CTM-15) Score 
 Interpersonal Support Evaluation List-12 
Score 
 Perceived Susceptibility Score 
 Illness Perception Questionnaire-Revised 
(IPQ-R) Consequences Sub-Scale Score 
 Perceived Barriers Score 
 Communication & Attitudinal Self-Efficacy 
Scale (CASE)-Cancer score 
 
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
We will conduct a single-site, single-arm phase II clinical trial of NDURE among HNC patients undergoing surgery and 
PORT (n=45; AA n=15; white n=30). NDURE is a theory-based, multi-level PN intervention consisting of three in-person, 
clinic-based sessions of manualized PN with multiple intervention components that target system- (care coordination), 
interpersonal- (social support), and individual- (HBM; perceived susceptibility, severity, barriers, self-efficacy) level 
health behavior theoretical constructs to reduce barriers to care, increase HNC care delivery, and improve clinical 
outcomes (timely, equitable PORT). NDURE will be delivered from surgical consultation to PORT initiation (~3 months). 
The three in-person NDURE navigation sessions, which are expected to take 30-60 minutes each, will coincide with the 
presurgical consult, hospital discharge, and 1st postoperative clinic visit, time points chosen to facilitate case 
identification and coordination across key care transitions. Measures of PORT delay will be analyzed overall (primary 
outcome) and for racial differences (secondary outcome). Measures of the preliminary clinical impact of NDURE on PORT 
barrier reduction and delivery of key HNC care processes will be collected (secondary outcome), feasibility (secondary 
outcome; accrual rate, NDURE completion rate, PN caseload), acceptability (secondary outcome; satisfaction with PN). 
Measures of the theoretical constructs underlying the multi-level, theory-based NDURE intervention will be compared 
pre- and post-intervention. Post-intervention qualitative work with patients and providers will help refine NDURE.  
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
We favor the single-arm design over a single-site randomized control trial (RCT) for the following reasons. First, 
randomizing patients to NDURE vs standard of care within a single site would contaminate the ‘control’ group due to 
unmeasured, off-target effects of NDURE on processes of care PI and culture, thereby producing an underestimation of 
NDURE’s true impact. Second, statistical models have shown that a single-arm design is preferred to a two-arm design 
for phase II trials in situations such as ours when the historical controls are well defined and the sample size is small30. 
Third, our design was chosen not to determine clinical efficacy, but rather to provide preliminary estimates  of clinical 
impact (as determined by the point estimates of rate of PORT delay relative to historical controls) and precision (margin 
of error) to design a larger scale multi-site cluster-randomized clinical trial to test the efficacy of NDURE31. Consistent 
with this study design is our limited sample size and the recognition that our exploratory, early phase trial will not 
produce definitive clinical conclusions32. 
 
4.3 
JUSTIFICATION FOR INTERVENTION 
The three in-person NDURE sessions, which are expected to take 30-60 minutes each, will coincide with the presurgical 
consult, hospital discharge, and 1st postoperative clinic visit, time points chosen to facilitate case identification and 
coordination across key care transitions. These timepoints also promote the feasibility of NDURE delivery as nearly 100% 
of patients attend these three visits (despite travel distance-related barriers33) since patients 1) cannot have surgery 
without their presurgical consult; 2) are hospitalized postoperatively; and 3) return for the 1st postoperative visit for 
drain/tube removal. 
 

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4.4 
END-OF-STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed the baseline assessment, at least two 
NDURE intervention sessions, and the final follow-up assessment.  
 
5 
STUDY POPULATION 
5.1 
INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
 
Patient and disease characteristics 
1. Age > 18 years at the time of screening 
2. Histologically or pathologically confirmed invasive SCC (or histologic variant) of the oral cavity, oropharynx 
(p16 positive, negative, or unknown), hypopharynx, larynx, unknown primary, paranasal sinuses, or nasal cavity. 
a. In situations in which the patient fulfills all other inclusion criteria but the biopsy shows SCC in-situ or 
moderate/severe dysplasia (without definitive evidence of invasive SCC), but the patient is scheduled to 
undergo curative intent surgery by the treating oncologic surgeon due to clinical suspicion of invasive 
SCC, the diagnosis of SCC-in situ or moderate/severe dysplasia is sufficient to full the pathologic 
diagnosis enrollment criterion. 
3. American Joint Committee on Cancer (AJCC) clinical stage grouping III-IV (8th edition) for patients with SCC of 
the oral cavity, p16-negative oropharynx, hypopharynx, larynx, paranasal sinuses, and nasal cavity; or AJCC 
clinical stage grouping III-IV (7th edition) for patients with p16-positive SCC of the oropharynx or unknown 
primary. 
a. At screening, AJCC clinical stage grouping should be determined based on a combination of physical 
exam, diagnostic evaluation with cross sectional imaging of the neck (computerized tomography (CT) 
and/or magnetic resonance imaging (MRI)) and/or 18-F-fluoro-deoxyglucose positron emission 
tomography (FDG PET) CT within 30 days 
b. In situations in which the patient fulfills all other inclusion criteria but the biopsy shows SCC in-situ or 
moderate/severe dysplasia (without definitive evidence of invasive SCC), but would otherwise have an 
appropriate clinical stage grouping as defined in criterion 5, the diagnosis of SCC-in situ or 
moderate/severe dysplasia is sufficient to full the staging enrollment criterion. 
4. No prior exposure to radiation therapy, with or without concurrent chemotherapy, for treatment of HNSCC in 
the definitive or adjuvant therapy settings 
 
Surgery and adjuvant therapy eligibility 
5. Plan for curative intent surgery at MUSC 
a. At screening, plan for curative intent surgical resection of the HNSCC at MUSC must be deemed likely 
by the treating surgeon and/or multidisciplinary tumor board, which must include a fellowship-trained 
head and neck oncologic surgeon 
6. Plan for PORT (at MUSC or non-MUSC) with or without concurrent chemotherapy following curative intent 
surgery 
a. At screening, plan for adjuvant therapy following curative intent surgical resection of the HNSCC at 
MUSC must be deemed likely by the treating surgeon and/or multidisciplinary tumor board, which must 
include a fellowship-trained head and neck oncologic surgeon, based on the clinical expectation of at 
least one of the following adverse features on final pathologic evaluation: extranodal extension (ENE), 
pT3 or pT4 primary, N2 or N3 nodal disease, nodal disease in levels IV or V, perineural invasion (PNI), or 
lymphovascular invasion (LVI) 
 
5.2 
EXCLUSION CRITERIA 
 

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An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Self-identified Hispanic ethnicity 
2. Presence of cognitive impairment that precludes participation 
3. Neoadjuvant immunotherapy or chemotherapy 
4. Failure to undergo curative intent surgery at MUSC 
5. Lack of indication for PORT (with or without concurrent chemotherapy) per National Comprehensive Cancer 
Network (NCCN) Guidelines based on the presence of at least one of the following adverse features on final 
pathologic evaluation: ENE, positive margin, pT3 or pT4 primary, N2 or N3 nodal disease, nodal disease in levels 
IV or V, PNI, or LVI 
 
Individuals across the lifespan will be included with the following exception: children (i.e., individuals under age 18) will 
be excluded. Children are not eligible to participate in the study for the following scientific reasons: 1) HNSCC is a rare 
pediatric malignancy; and 2) the care delivery experiences of children with HNSCC are likely very different from those of 
adults. The age distribution included in the study (all ages >/= 18) will allow us to evaluate the feasibility and 
acceptability of NDURE in individuals of across the lifespan. 
 
Patients of non-white, non-AA racial groups (e.g. Asian American, Native American) will be excluded from the clinical 
trial of NDURE. Our decision to focus only on white and AA patients (and exclude other racial groups) is justified by the 
following considerations: 1) In terms of timely PORT, the racial disparities are largest among white compared to AA 
HNSCC patients (nationally and at MUSC); 2) The barriers causing racial differences in time to PORT among AAs and 
other racial groups may be different, necessitating a different patient navigation intervention; 3) Other non-white, non-
AA racial groups make up only 1% of HNSCC patients treated at MUSC. As a result, finding a sufficient number of 
patients who are non-AA racial minorities to participate in the RCT of NDURE would be challenging. Patients who self-
identify as being of Hispanic ethnicity will be excluded from the clinical trial of NDURE. Although Hispanic ethnicity is a 
risk factor for delayed PORT, we justify our exclusion of Hispanic patients from the clinical trial for the following reasons: 
1) The barriers causing racial differences in time to PORT among AAs and Hispanics are likely different (e.g. language); 2) 
Hispanic HNSCC patients account for only 3% of patients at MUSC. As a result, finding a sufficient number of Hispanic 
patients to participate in the clinical trial of NDURE would be challenging. 
 
5.3 
LIFESTYLE CONSIDERATIONS 
N/A 
 
5.4 
SCREEN FAILURES 
 
Screen failures are defined as participants who consent to participate in this study but are not subsequently assigned to 
the study intervention or entered in the study. Individuals who do not meet the criteria for participation in this trial 
(screen failure) because of meeting one or more exclusion criteria will not be rescreened. 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Recruitment for the single-site, single-arm, pilot trial of NDURE will occur using a clinic-based approach from the MUSC 
Head and Neck Tumor Center, a high-volume academic HNC program at the NCI-designated Hollings Cancer Center. 
Research staff will use cancer center registry data, discussion with the HNC clinical team, and the electronic medical 
record (EMR) to identify patients who meet study inclusion criteria. Research staff will then review clinic rosters to 
identify eligible patients who are scheduled for an appointment in the Head and Neck Tumor Center. Study recruitment 
will be facilitated through the use of tested, structured protocols. Chanita Hughes-Halbert, PhD has evidenced-based 
strategies that have been successfully employed to recruit AA cancer patients to therapeutic trials. We will also use 
structured protocols from the principal investigator (Evan Graboyes, MD) and co-mentor Katherine Sterba, PhD, MPH. 
These protocols have been successfully employed and refined for clinic-based recruitment of patients with HNC to 

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participate in behavioral research during treatment periods. Recruitment is expected to be enhanced by the active 
clinical practice of the PI. 
 
Prior to studying the NDURE intervention in a clinical trial, we will pre-test our intervention in n=3 patients to ensure 
proper implementation into clinical workflow. These patients will participate in the intervention and outcome 
assessment only for the purposes of pre-testing and assessing our implementation into clinical workflow but not for the 
purposes of analysis towards any of the study endpoints. 
 
We propose to accrue 45 patients (white, n=30 and AA, n=15) to the study over 13 months. Based on data from 
MUSC/HCC for 2018, it is expected that 125 patients/year will be eligible for the study, of whom 28 (22%) are expected 
to be AA and 97 (78%) are expected to be white. Based on the PI and study team’s prior experience recruiting and 
enrolling for similar studies embedded into clinical care, we anticipate that 50% of eligible patients will accrue to this 
study. Based on this 50% accrual rate, over the course of 13 months, we would expect to accrue 68 patients (n=15 AAs; 
n=53 white). Thus, by conservative estimates with appropriate over-sampling of AAs, our overall accrual target (n=45) 
and for the AA racial subgroup (n=15) appear highly feasible in the allocated 13 month accrual period. 
 
Because we plan to enroll consecutive patients for this clinic-based intervention, one potential concern relates to 
systematic, non-random differences between patients who participate in NDURE and patients who decline to 
participate. Enthusiastic, health-motivated patients may enroll while marginalized, burdened patients who distrust the 
medical system may preferentially decline. Alternatively, patients with few/no perceived barriers may 
disproportionately decline the intervention due to perceived lack of need while burdened patients participate because 
of the perceived need. Whichever, if any, situation occurs, our approach ensure that we will still be well positioned 
because we will collect information about which patients enroll/decline and their reasons for enrolling/declining to help 
refine NDURE for future dissemination. 
 
Three strategies will be used to ensure retention of enrolled patients in the study. First, supportive and frequent 
interactions between the participant and navigator are expected to occur throughout NDURE, which should help 
mitigate against retention problems (for those in the NDURE arm). Second, we have accounted for the burden of 
surveys/questionnaires while patients are on treatment to ensure that the expected time commitment from surveys is 
reasonable and that the study interactions will be scheduled at a convenient time for patients (usually while at MUSC for 
clinical care already). Finally, remuneration will also occur on a schedule that is weighted towards providing the majority 
of the compensation at the end of the study time period. 
 
Retention of subjects is not expected to be problematic since NDURE is embedded into clinical care and patients will be 
actively on treatment during the study. The scheduled timepoints of navigator-participant interaction (initial surgical 
consultation, prior to hospital discharge, first clinic visit after hospital discharge) were chosen because these are 
situations in which the likelihood of contact is ~100%. Although challenges with retention for cancer studies due to 
mortality (overall and disease-specific) and treatment toxicity are potentially problematic, we do not think that they will 
limit retention in this feasibility study of NDURE. The rate of on-treatment mortality (during surgery or adjuvant therapy) 
is quite low (<5%) and the study follow-up does not extend past the completion of therapy. Thus, lack of retention due 
to mortality is not expected to be significant. Treatment toxicity is potentially a problem, as patients may not want to 
answer surveys while undergoing treatment or choose to withdraw due to competing treatment demands. We do not 
expect this to be a problem, however, because NDURE will be integrated into routine clinical care and thus should not 
create an excess time burden for patients. In fact, it is likely that participation in the intervention, which is expected to 
improve care coordination and decrease barriers to care, will make this potential source of dropout less likely than other 
intervention trials. Using NDURE to address individualized barriers to timely HNC treatment is a significant strength and 
innovation of the study and will likely also improve retention relative to historical rates. 
 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION 

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6.1.1  STUDY INTERVENTION OR EXPERIMENTAL MANIPULATION DESCRIPTION 
NDURE is a theory-based, multi-level PN intervention consisting of three in-person, clinic-based sessions of manualized 
PN with multiple intervention components that target system- (care coordination), interpersonal- (social support), and 
individual- (HBM; perceived susceptibility, severity, barriers, self-efficacy) level health behavior theoretical constructs to 
reduce barriers to care, increase HNC care delivery, and improve clinical outcomes (timely, equitable PORT). The NDURE 
intervention components and targeted theoretical constructs are outlined in Table 1. NDURE will be delivered from 
surgical consultation to PORT initiation (~3 months). The three in-person NDURE navigation sessions, which are expected 
to take 30-60 minutes each, will coincide with the presurgical consult, hospital discharge, and 1st postoperative clinic 
visit, time points chosen to facilitate case identification and coordination across key care transitions. Contact beyond the 
three prescribed in-person sessions will occur with a frequency and modality (e.g. text message, email, etc.) dictated by 
patient and navigator need. During the first in-person session, the navigator will 1) elicit barriers and facilitators to 
timely PORT from the patient, caregiver, and provider, 2) develop the personalized barrier reduction plan (BRP), review 
it with the patient, caregiver, and provider, and 3) implement the BRP. At the two subsequent in-person sessions, the 
navigator will review and update the BRP in an iterative, dynamic fashion, identifying new barriers and systematically 
tracking resolution of prior barriers until the start of PORT. The Navigator Manual provides a structured resource to 
guide intervention delivery and enhance reproducibility. The Patient Guide  is 1) literacy-level appropriate, 2) 
personalized for each patient’s care pathway and BRP, 3) updated longitudinally as the patient progresses along the 
cancer continuum, and 4) available to patients in print and/or electronically via the patient portal in the EMR. 
 
 
Table 1. NDURE Intervention Components 
Component                         Description 
Theoretical Target 
Clinical Tool 
NDURE 
Navigation 
Sessions 
Three manualized sessions in which the navigator 
develops and enacts a personalized BRP. While 
performing the BRP, the navigator will facilitate care 
coordination, 
link 
patients 
to 
resources 
and 
instrumentally assist with barrier mediation, educate 
patients on the risk and health consequences of PORT 
delay, 
and 
provide 
verbal 
reinforcement 
and 
demonstration to enhance patients’ self-confidence to 
achieve timely PORT 
-Care coordination 
-Instrumental support 
-Informational support 
-Perceived susceptibility 
-Perceived severity 
-Perceived barriers 
-Perceived self-efficacy 
NDURE 
Navigator 
Manual 
-Contact information for HNC providers in SC 
-Taxonomy of barriers to timely PORT 
-Resource library matched to key barriers 
-Care coordination 
-Perceived barriers 
-Support 
NDURE Patient Guide 
-Personalized contact information for HNC team 
-Resources to address barriers in BRP 
-Personalized PORT Timeline 
-At-risk population and tailored risk of PORT delay 
-Health consequences of delayed PORT 
-Personalized BRP 
-Care coordination 
-Instrumental support 
-Informational support 
-Perceived susceptibility 
-Perceived severity 
-Perceived barriers 
System Changes 
Documentation 
Structured EMR flowchart to document barriers and 
BRP that is accessible to HNC care team 
Care coordination 
Conferences 
Multi-D weekly review of PORT timeline adherence  
Care coordination 
Patient Tracking 
Real-time EMR tracking of care delivery processes 
Informational support 
Reporting 
Monthly PORT delay run charts at Tumor Board 
Informational support 
BRP: Barrier reduction plan, EMR: electronic medical record, HNC: Head and neck cancer, PORT: Postoperative 
radiation therapy, SC: South Carolina 

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Culture, the set of shared and socially transmitted beliefs and values regarding the nature of time, social relationships, 
and supernatural entities that are passed between generations and shared among members of ethnic and racial 
groups34 is a critical determinant of cancer prevention, control, and treatment behaviors as well as cancer-related 
psychological and behavioral outcomes35. As a result, NDURE navigation sessions and intervention components will be 
delivered in a culturally appropriate manner. We will also use validated measures of key cultural variables to understand 
the role that culture plays in the delivery, acceptability, and clinical impact of NDURE. 
 
6.1.2 ADMINISTRATION AND/OR DOSING 
NDURE will be delivered in one-on-one, face-to-face sessions between the navigator and the participant in a clinic- or 
hospital-based setting. The NDURE intervention consists of three in-person navigation sessions, which are expected to 
take 30-60 minutes each. The three clinic- or hospital-based sessions will coincide with the presurgical consult, hospital 
discharge, and 1st postoperative clinic visit, time points chosen to facilitate case identification and coordination across 
key care transitions. Contact beyond the three prescribed in-person sessions will occur with a frequency and modality 
(e.g. text message, email, etc.) dictated by patient and navigator need. A single dedicated navigator with no competing 
clinical or administrative responsibilities outside of this trial will deliver the NDURE intervention. Full-dose will consist of 
completing all three NDURE navigation sessions. 
 
6.2 
FIDELITY 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
The navigator, supervised by Dr. Graboyes, will keep a tracking log with encounters (number, modality of each session), 
time (direct with patient, indirect to complete BRP), barriers (number, type), and BRP activity (action, outcome)31. In-
person NDURE sessions will be audio-recorded and randomly selected sessions (20%) will be reviewed by Dr. Graboyes 
to ensure fidelity. Bi-monthly case conferences with the navigator, Dr. Graboyes, and Dr. Hughes-Halbert will further 
ensure continued high-quality PN. 
 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
N/A 
 
6.4 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
Participants’ adherence with study procedures will be tracked by attendance at intervention visits. 
 
6.5 
CONCOMITANT THERAPY 
N/A 
 
6.5.1 RESCUE THERAPY 
N/A 
 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL. 
7.1 
DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
N/A 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue a participant from the study for the following reasons: 
 
Significant study intervention non-compliance, unless varying compliance is an aspect of the study objectives  

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 
Lost-to-follow up; unable to contact subject (see Section 7.3, Lost to Follow-Up) 
 
Any event or medical condition or situation occurs such that continued collection of follow-up  study data would 
not be in the best interest of the participant or might require an additional treatment that would confound the 
interpretation of the study 
 
The participant meets an exclusion criterion (either newly developed or not previously recognized) that 
precludes further study participation 
 
The reason for participant discontinuation or withdrawal from the study will be recorded on the Case Report Form (CRF). 
Subjects who sign the informed consent form and are assigned to the study intervention but do not receive the study 
intervention may be replaced.  Subjects who sign the informed consent form and receive the study intervention, and 
subsequently withdraw, or are discontinued from the study, will be replaced in the following circumstances as described 
in (Section 5.4, Screen Failures) 
 
Patient is expected to have surgery and then decides to pursue a nonsurgical treatment 
 
Patient is expected to have surgery at MUSC and then decides to pursue treatment elsewhere 
 
PORT is expected based on the clinical TNM classification, but analysis of the pathology specimen after surgery 
changes the pathologic TNM classification and/or adverse features such that PORT is not indicated per National 
Comprehensive Cancer Network (NCCN) Guidelines. 
 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for two scheduled visits and study staff are 
unable to contact the participant after at least 3 attempts.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
 
The site will attempt to contact the participant, reschedule the missed visit within 2 weeks, counsel the 
participant on the importance of maintaining the assigned visit schedule and ascertain if the participant wishes 
to and/or should continue in the study 
 
Before a participant is deemed lost to follow-up, the investigator or designee will make every effort to regain 
contact with the participant (where possible, 3 telephone calls and, if necessary, a certified letter to the 
participant’s last known mailing address or local equivalent methods). These contact attempts will be 
documented in the participant’s medical record or study file.  
 
Should the participant continue to be unreachable, he or she will be considered to have withdrawn from the 
study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
Primary Endpoint 
Initiation of postoperative PORT > 6 weeks after surgery is defined as more than 42 calendar days from the time of the 
definitive surgical resection to the initiation of radiation therapy. In situations in which the surgical management of the 
primary tumor and the neck are staged (i.e. occur on two different calendar days), the date of the surgery for the 
primary tumor will be used. In situations in which an additional surgical resection is required (e.g. re-resection of 
positive margins to clear residual disease), the date of the earlier (i.e. attempted definitive) surgical procedure will be 
used to determine the target start date for PORT. 
 

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Secondary Endpoints 
Clinical Outcomes 
Racial disparities in initiation of PORT > 6 weeks after surgery is defined as the difference in the rate of initiation of PORT 
> 6 weeks after surgery between white and AA HNC patients. 
 
Days between surgery and the start of PORT is defined as the time, in days, between the date of definitive surgical 
resection to the initiation of radiation therapy. All of the criteria used to adjudicate the date of the definitive surgical 
procedure described for the primary outcome measure will be applied to this measure. 
 
Barriers resolved is the number of barriers identified by the navigator that are resolved during the NDURE intervention, 
as determined by the navigator log. 
 
Unresolved barriers is the number of barriers identified by the navigator that are not resolved during the NDURE 
intervention, as determined by the navigator log. 
 
Pre-Surgical Radiation Consultation is defined as the attendance by the patient at a consultation with a radiation 
oncologist (at MUSC or elsewhere) prior to surgery to discuss RT in the definitive or adjuvant setting 
 
Pre-Radiation Therapy Dental Extractions is defined as the extraction of teeth prior to discharge from the index 
hospitalization for the definitive surgical procedure. Patients who are edentulous are not evaluable for this measure. 
 
Surgery to Pathology Report </= 7 days is defined as the production of the pathology report from the definitive surgical 
procedure within the EMR within 7 calendar days of the definitive surgical procedure. Addenda to the pathology report 
at the request of the HNC team (e.g. tumor p16 status) are not counted in this measure. 
 
Surgery to PORT Referral </=  10 days is defined as the placement of a referral for PORT, at MUSC or elsewhere, within 
10 calendar days of the definitive surgical procedure. 
 
RT Referral to Consult  </=  10 days is defined as the evaluation of the patient at a postoperative consultation with a 
radiation oncologist within 10 calendar days of the referral being placed (or postoperative appointment being scheduled 
in cases in which care has been established and the return visit is no longer a consultation). The consultation may occur 
in the clinic or the hospital depending upon clinical circumstances. 
 
RT Consult to Initiation </= 21 days is defined as the initiation of PORT within 21 calendar days of the patient being 
evaluated by a radiation oncologist for PORT. 
 
Feasibility 
NDURE Accrual is defined as the proportion of eligible patients who enroll in NDURE 
 
NDURE Completion is defined as a participant completing the baseline assessment, at least two NDURE intervention 
sessions, and the final follow-up assessment 
 
Navigation Session Completion is the number of NDURE navigation sessions completed by a participant 
 
Navigator Caseload is the number of simultaneous cases (on-trial participants) being navigated by the NDURE navigator 
 
Navigator Time Allocation (Direct) is the time (in minutes), that the NDURE navigator spends directly interacting with the 
patient to identify and address barriers to timely, equitable postoperative radiation therapy 
 
Navigator Time Allocation (Indirect) is the time (in minutes), that the navigator spends  generating and enacting each 
Barrier Reduction Plan that is not directly interacting with the patient 

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Acceptability 
Satisfaction with the Interpersonal Relationship with the Navigator Scale is, a validated, 9-item measure of the 
satisfaction of the interpersonal relationship with the patient navigator that has been used in prior studies of PN36,37. 
 
Satisfaction with Logistical Aspects of Navigation Scale is a validated, 26-item measure of the satisfaction of the logistical 
aspects of PN that has been used in prior studies of PN38. 
 
Health Behavior Constructs 
Care Transition Measure-15 (CTM-15) is a validated, psychometrically sound 15-item, unidimensional measure of care 
transitions across the healthcare system that is consistent with the concept of patient-centeredness and useful from an 
organization perspective for the purpose of performance measurement and quality improvement39. Higher scores reflect 
higher levers of care integration and coordination. 
 
Communication & Attitudinal Self-Efficacy Scale (CASE)-Cancer is a validated, psychometrically sound 12-item scale that 
addresses three domains of self-efficacy in cancer care (understanding and participating in care, maintaining a positive 
attitude, and seeking and obtaining information)40. The CASE-Cancer scale has been used extensively in PN studies to 
measure perceived self-efficacy10,31,41. Responses are on a 4-point Likert scale with higher scores indicating higher levels 
of self-efficacy. 
 
Interpersonal Support Evaluation List-12 (ISEL-12) is a validated, 12-item assessment of three domains of interpersonal 
support42 that has been used to assess support in prior PN studies43. Items are rated on a 4-point Likert scale with higher 
scores indicating more support. 
 
Perceived Susceptibility Questionnaire is modified version of a validated 3-item perceived susceptibility subscale for 
mammography screening44 to assess perceived susceptibility for delays starting PORT after HNC surgery. Items are rated 
on a 5-point Likert scale with higher scores indicating higher perceived susceptibility. 
 
Illness Perception Questionnaire-Revised (IPQ-R) consequences subscale (HNC modification). The IPQ-R consequences 
subscale is easily modifiable to asses disease-specific perceived severity45.The IPQ-R is a validated assessment of a 
patient’s self-representation of the health consequences of their illness46. It is scored using a 5-point Likert scale with 
higher scores indicate higher perceived severity. 
 
Perceived Barriers Questionnaire is a self-report measure of the presence/absence of pre-specified barriers to cancer 
care (yes/no). The questionnaire has been used extensively to assess perceived barriers in prior PN studies11,31,41,47. 
 
Covariates 
Behavioral Risk Factor Surveillance Survey (BRFSS) Demographics. The BRFSS is the nation’s premier health-related 
survey that collects data about health-related risk behaviors from US residents. The demographic section from the 
BRFSS will be used (in-person) to ascertain participant sex, age, race, marital status, insurance, educational attainment, 
living situation, zipcode, phones for personal use, employment, and annual household income48. 
 
BRFSS Tobacco Use and Alcohol Consumption. The tobacco use and alcohol consumption sections of the BRFSS will be 
used (in-person) to characterize total cigarette exposure, current cigarette use, quit attempts, days of alcohol 
consumption, average drinks/day, frequency of > 5 drinks, and maximum number of drinks. 
 
Clinical and Oncologic Characteristics. Clinical characteristics will include comorbid medical conditions, and cancer 
history. Oncologic characteristics will include HNC tumor subsite, HNC tumor histology, p16/human papillomavirus (HPV) 
tumor status, American Joint Committee on Cancer TNM Class and overall stage grouping, type of ablative surgery, type 
of reconstruction, treatment dates, facility of planned adjuvant therapy, and adjuvant treatment type planned (adjuvant 
radiation or chemoradiation). 

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Figure 1. Margin of Error Rates of 
Delayed PORT. Margin of error for rates 
of delayed PORT for overall cohort and 
white and African American subgroups in 
the single-arm NDURE pilot study. 
 
Barrier Load Survey will measure 1) the number of barriers identified in the BRP during NDURE; and 2) the type of 
barrier in our modified version of existing PN logs11,31,47 
 
Cultural Factor Survey is a validated, psychometrically sound questionnaire consists of three subscales assessing 
temporal orientation (5 items), collectivism (6 items), and religiosity (9 items)49. Prior PN studies have used these scales 
to measure cultural factors50. 
 
MD Anderson Symptom Inventory-Head Neck (MDASI-HN) is a validated, psychometrically sound, 28-item multi-
symptom patient-reported outcome measure for clinical and research use that assesses the severity of symptoms 
experienced by patients with cancer (including 9 HNC-specific symptoms), and the associated interference with daily 
living caused by these symptoms. Higher scores indicate more severe symptom/symptom interference51. 
 
 
9 
STATISTICAL CONSIDERATIONS  
9.1 
STATISTICAL HYPOTHESES 
 
 
Primary Endpoint(s):  
Because this is a pilot study generating preliminary data, our single-arm trial is not powered to detect a pre-specified 
improvement (i.e. reduction) in the rate of delayed PORT with NDURE. As such, the primary endpoint will be assessed via 
descriptive statistics. Hypotheses will be generated from the preliminary data for testing in future studies. 
 
 
Secondary Endpoint(s): 
Initiation of postoperative PORT > 6 weeks after surgery 
We hypothesize that, compared to historical control data for patients undergoing surgery for HNC at MUSC followed by 
PORT between 2014-2016, patients who receive NDURE will have a decreased rate of PORT delays (initiation of PORT > 6 
weeks after surgery). 
 
Alternatively, our null hypothesis is that there will be no difference in the rate of PORT delay between patients who 
receive NDURE when compared to historical control data for patients undergoing surgery for HNC at MUSC followed by 
PORT between 2014-2016. 
 
Initiation of postoperative PORT > 6 weeks after surgery 
We hypothesize that, compared to historical control data for 
patients undergoing surgery for HNC followed by PORT in the 
National Cancer Database between 2006-2014, patients who receive 
NDURE will have a decreased rate of PORT delays (initiation of PORT 
> 6 weeks after surgery). 
 
Alternatively, our null hypothesis is that there will be no difference 
in the rate of PORT delay between patients who receive NDURE 
when compared to historical control data for patients undergoing 
surgery for HNC followed by PORT in the National Cancer Database 
between 2006-2014. 
 
9.2 
SAMPLE SIZE DETERMINATION 
Because this is a pilot study generating preliminary data, our single-
arm trial is not powered to detect a pre-specified improvement (i.e. 
reduction) in the rate of delayed PORT with NDURE. Rather, we 

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justify our sample size based on the desired precision (as measured by the half-width of a 95% CI, also known as the 
margin of error) in estimates of PORT delay rates.  Fig. 1 shows the margin of error for proportions ranging from 0 to 0.5 
for n=15, 30 and 45 the sample sizes for AA and white patient subgroups and the entire cohort, respectively. Because 
the margin of error for proportion p is equivalent to that for proportion 1 – p, we limit Figure 1 to proportions ranging 
from 0 to 0.5.) For PORT delay rate estimates based on the entire sample, the maximum margin of error (smallest 
precision) is 0.15 occurring for a proportion of 0.5, with the margin of error decreasing (precision increasing) for 
proportions closer to 0 or 1. For example, the 95% CI for an observed PORT delay rate of 50% is 35% to 65%, indicating 
an acceptable level of uncertainty in the estimate and providing adequate precision to allow accurate design of a 
randomized trial evaluating the NDURE intervention. The margin of error is greatest for the subpopulation of AA patients 
because of the smaller sample size. Nonetheless, the maximum margin of error at an observed proportion of 50% is 
approximately 0.25 (95% CI = 25% to 75%) which is sufficient information to adequately design a randomized study to 
evaluate the efficacy of NDURE in these subpopulations. We considered extending the study accrual to increase 
enrollment to targets of 75 patients (white, n=50 and AA, n=25). The maximum margin of error for a proportion of 0.5 
would decrease to 0.11 (relative to 0.15 with enrollment targets of n=45), which is a negligible improvement. The 95% CI 
for an observed PORT delay rate of 50% in the larger (n=75) cohort would be 39% to 61% (relative to 35% to 65% in the 
n=45 cohort), which again does not significantly improve precision in terms of accurate design of a randomized trial 
evaluating the NDURE intervention. The AA sub-population has the greatest margin of error because of the smaller 
sample size. By increasing enrollment from n=15 AAs to n=25 AAs, the margin of error would only decrease from 0.25 
(95% CI = 25% to 75%) to 0.20 (95% CI = 30% to 70%) at an observed proportion of 50%, which again does not 
significantly improve the ability to design a randomized study to evaluate the efficacy of NDURE in these subpopulations. 
Given the volume of eligible patients at MUSC33 and historical participation rates52, we consider n=45 (AA n=15; white 
n=30) subjects to be a reasonable sample size target for patients who enroll and complete the study. This approach and 
data analysis plan recognizes that early phase trials do not produce definitive clinical conclusions32, but provide 
information to ascertain whether additional large-scale clinical trials assessing efficacy are warranted and estimates of 
precision to inform future study design53. 
 
Every effort will be made to minimize missing data and lost-to-follow-up participants. Participants will complete 
assessments at baseline and post intervention using an iPad-based REDCap collection method. The program coordinator 
will attempt to contact patients at least three times using a variety of methods of communication (e.g. text message, 
phone call, email, mail, etc) to complete outcome measures. This method resulted in 100% instrument completion in 
prior studies conducted by our team. Patients in the ITT population for whom the primary endpoint is not evaluable due 
to loss to follow-up will be considered NDURE failures, and their time to PORT will be treated as exceeding 6 weeks for 
the purposes of analysis (a very conservative approach for this single-arm, phase II pilot study. In the event that missing 
data occur for other endpoints, we will address them via standard multiple imputation procedures. In general, less than 
10% missing data has little impact on study power and does not induce bias regardless of the missing data mechanism. If 
missing data is greater than 10%, it will be imputed using Markov Chain Monte Carlo (MCMC) methods. The data 
augmentation will be applied to Bayesian inference with missing data by repeating imputation step (i.e., simulating the 
missing values based on the observation) and step for exploring the posterior distribution based on the complete sample 
estimates obtained from the imputation step. 
 
Our plan to accrue 45 patients (white, n=30 and AA, n=15) to the study over 13 months is highly feasible. Based on data 
from MUSC/HCC for 2018, it is expected that 125 patients/year will be eligible for the study, of whom 28 (22%) are 
expected to be AA and 97 (78%) are expected to be white. Based on the PI and study team’s prior experience recruiting 
and enrolling for similar studies embedded into clinical care, we anticipate that 50% of eligible patients will accrue to 
this study. Based on this 50% accrual rate, over the course of 13 months, we would expect to accrue 68 patients (n=15 
AAs; n=53 white). Thus, by conservative estimates with appropriate over-sampling of AAs, our overall accrual target 
(n=45) and for the AA racial subgroup (n=15) appear highly feasible in the allocated 13 month accrual period. 
 
9.3 
POPULATIONS FOR ANALYSES 
 

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Prior to studying the NDURE intervention in a phase II clinical trial, we will pre-test our intervention in n=3 patients to 
ensure proper implementation into clinical workflow. These patients will participate in the intervention and outcome 
assessment only for the purposes of pre-testing and assessing our implementation into clinical workflow but not for the 
purposes of analysis towards any of the study endpoints. 
 
 
For the efficacy analysis, we will utilize a modified intention-to-treat (ITT) population. Participants will be part of the 
modified ITT population as defined by the following criteria: 
1. Randomized to NDURE or Usual Care 
2. Receipt of curative intent surgery at MUSC 
3. Indication for PORT (with or without concurrent chemotherapy) per NCCN Guidelines based on the presence of 
at least one of the following adverse features on final pathologic evaluation: ENE, positive margin, pT3 or pT4 
primary, N2 or N3 nodal disease, nodal disease in levels IV or V, PNI or LVI 
 
As such, the modified ITT analytic population addresses the fact that eligibility, registration, randomization, and delivery 
of a portion of the intervention (NDURE or Usual Care) occur prior to definitive treatment of the HNSCC. However, the 
primary study objective (and endpoint) are defined and evaluable only for patients who undergo surgery for HNSCC and 
have an indication for adjuvant therapy (which can only be definitively known following surgical resection). As such, we 
expect that a predictable subset of patients will be enrolled in the study, based on meeting all inclusion, be randomized 
to NDURE or Usual Care, receive a portion of the intervention (NDURE Visit 1) and then subsequently develop a study 
exclusion criterion based on interval information that becomes available later in the clinical course that cannot be 
known at the time of study enrollment and registration, namely: 
 
failure to undergo curative intent surgery at MUSC (exclusion criteria #4) 
 
lack of indication for PORT (with or without chemotherapy) per NCCN Guidelines (exclusion criteria #5) 
 
As such, patients who meet study inclusion criteria but subsequently develop exclusion criteria #4 or #5 during the 
course of the study will be replaced since the primary endpoint is anchored to findings that occur after analysis of the 
pathologic specimen obtained during surgery. Patients in the modified ITT population for whom the primary endpoint is 
not evaluable due to loss to follow-up will be considered navigation failures, and their time to PORT will be treated as 
exceeding 6 weeks for the purposes of analysis. 
 
We will also perform an efficacy analysis on the per-protocol analytic dataset, a subset of the modified ITT population 
who completed all 3 NDURE study sessions. These patients are judged to have complied with the protocol sufficiently to 
ensure that these data would be likely to represent the effects of the NDURE intervention according to the underlying 
scientific model. 
 
9.4 
STATISTICAL ANALYSES 
9.4.1 GENERAL APPROACH 
We will construct graphical displays and calculate descriptive statistics (e.g. frequencies and percent for categorical 
variables, and mean, median, standard deviation, and range for continuous variables). Covariates will be specified 
below. For inferential tests, we will use a p-value of 0.05, two-sided, and 95% confidence intervals (CIs) to assess 
statistical significance (Type I error). Normality of the data will be assessed before underlying statistical procedures will 
be performed. We will evaluate variable transformations as needed to satisfy assumptions and consider transformations 
of variables to induce approximate normality and stabilize variance as needed. Nonparametric tests will be applied when 
appropriate. 
 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 

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For the primary endpoint, delays starting PORT, the proportion of patients who start PORT more than 6 weeks after 
surgery and corresponding 95% CI will be calculated for the overall cohort and for white and AA subgroups separately. 
We will calculate racial disparities in PORT delay by comparing the difference in the rate of PORT delay (more than 6 
weeks after surgery) between white and AA patients. 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
We will analyze time-to-PORT as a continuous variable and estimate median time-to-PORT for the cohort overall and for 
AA and white subgroups using Kaplan-Meier curves with Greenwood variance estimation for the corresponding 95% CIs. 
We will calculate racial disparities in time-to-PORT by comparing the difference in median time-to-PORT between white 
and AA patients. 
 
We will compare the findings from our phase II trial of NDURE (rate of PORT delay; median time-to-PORT for the cohort 
overall and for racial disparities in each endpoint) to historical controls (at MUSC33 and nationally6) using Fisher’s exact 
test. If the upper bound of the 95% CI for the rate of delayed PORT (and racial disparities in delayed PORT) is at or below 
the lower bound of the 95% CI for the similar endpoint in our historical controls, we can conclude that the preliminary 
estimates of the therapeutic activity of NDURE (i.e. clinical benefit) suggest that further rigorous testing of the efficacy of 
the PN intervention in a larger clinical trial is warranted based on these phase II results. We will nevertheless interpret 
findings relative to historical control cautiously given that the data do not arise from a randomized trial. 
 
For the secondary endpoints of barrier reduction and unresolved barriers, we will calculate the proportion of unresolved 
barriers and the frequency of unresolved barriers (respectively) at the end of NDURE, consistent with prior PN studies47. 
We will use logistic regression to assess the relationship between unresolved barriers and the rate of PORT delay 
(primary endpoint), controlling for covariates listed in Section 8.1. 
 
Secondary endpoints for feasibility, acceptability, fidelity and HNC care delivery will be analyzed as follows. For study 
accrual, we will calculate the proportion and frequency of eligible patients who accrue (overall, white, and AA). Given its 
pilot nature, the study is not designed to evaluate racial differences in accrual, although reasons for study decline will be 
collected, analyzed by race, and used to refine recruitment. NDURE completion will be analyzed as 1) the percentage of 
enrolled patients who attend all three in-person NDURE sessions and 2) the proportion of three in-person NDURE 
sessions that are completed. For navigator caseload, we will consider the frequency of simultaneous cases navigated. 
Navigator time allocation for direct and indirect time, as well as patient-report measures of satisfaction with navigation 
(acceptability) will be summarized as described above for continuous data. NDURE fidelity will be analyzed as the 
proportion of enrolled patients who have a BRP documented in the EMR. For HNC care delivery processes, we will 
calculate the proportion of patients receiving each key HNC care delivery process. 
 
For secondary endpoints evaluating the theoretical constructs underlying NDURE (care coordination, support, perceived 
susceptibility, severity, barriers, and self-efficacy), we will estimate the mean change in each measure (pre-post) as well 
as standard deviations and 95% CIs for each; comparisons will be conducted using Wilcoxon sign-rank test. Baseline 
levels of each dependent variable will be controlled in each model; additional covariates will be considered by examining 
associations between potential covariates and each dependent variable using linear regression (p < .10 where the 
change in each outcome measure is the dependent variable). This method will allow estimation of intervention effects 
while adjusting for potential confounders. 
 
9.4.4 SAFETY ANALYSES 
N/A 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
N/A 
 
9.4.6 PLANNED INTERIM ANALYSES  

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N/A 
9.4.7 SUB-GROUP ANALYSES 
Planned sub-group analyses of the primary endpoint will occur based on age and sex to evaluate the impact of inclusion 
across the lifespan and sex as a biologic variable. Historical data have not established an association between either age 
or sex with the primary endpoint6. Given the importance of race to the study objectives, analysis of the primary 
endpoint by race is evaluated as a secondary objective instead of planned subset analysis. Additional planned subset 
analyses will evaluate the impact of the NDURE intervention on the primary endpoint based on insurance status and 
fragmentation of care between the surgical facility and radiation facility, both of which have been described as risk 
factors for delayed PORT6. As such, both of these variables have the potential to confound the effect of the intervention 
were they to be imbalanced in a future RCT. As such, evaluating their impact on the primary endpoint in this study 
would allow for rational stratification in planned future RCTs. 
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
Individual participant data will not be listed by measure and time point. 
 
9.4.9 EXPLORATORY ANALYSES 
N/A 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
We will obtain full written Informed consent from patients enrolling in the study. Informed consent will occur 
via face-face discussion between one of the study team members designated to perform informed consent and the 
potential study participant.  After describing the study and allowing the potential participants to ask any questions, we 
will schedule interviews with those who are eligible and interested in participating in the study. Participant will have 
time to read the informed consent form and HIPAA document on their own.  Consents will be written in simple, easy-to-
understand language and obtained on the day of enrollment by the trained study coordinator. A study team member 
will answer any questions about the study and participants will be asked to sign the consent and HIPAA forms. All 
participants will sign informed consent forms before the interview.  All participants will receive a copy of their informed 
consent and HIPAA forms for their records. The informed consent process will take place in a private room in the 10th 
floor Rutledge Tower Head and Neck Cancer Clinic or in a private room in the HCC. Only the study participant will 
provide informed consent. Subjects will be allowed up to one week to decide whether to participate in the study. 
 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
[This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. Written 
notification, documenting the reason for study suspension or termination, will be provided by the suspending or 
terminating party to study participants, investigator, funding agency, and regulatory authorities. If the study is 
prematurely terminated or suspended, the PI will promptly inform study participants, the IRB, and sponsor/funding 
agency and will provide the reason(s) for the termination or suspension. Study participants will be contacted, as 
applicable, and be informed of changes to study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
Determination of unexpected, significant, or unacceptable risk to participants 
 
Insufficient compliance of study staff to the protocol (e.g. significant protocol violations) 
 
Data that are not sufficiently complete and/or evaluable 
 

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The study may resume once concerns about safety, protocol compliance, and data quality are addressed, and satisfy the 
funding agency, sponsor, IRB, Food and Drug Administration (FDA), or other relevant regulatory or oversight bodies 
(OHRP, data safety monitoring board (DSMB)). 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
To help protect participant confidentiality, we will assign a unique study ID number to each subject’s information in 
place of his/her name and will label data collection forms only with the ID number. All hard copy and electronic files will 
be stored appropriately using double-locked methods and password-protection. Only the study team member will have 
access to study records. Participant data will be collected and recorded on either a password-protected electronic data 
capture format (Research Electronic Data Capture; REDCap) or paper-based forms depending upon patient preference. 
For the paper collection data method, the data collection form will be labeled only with the participant's unique study ID 
number, and then stored within locked drawers in a locked office. The information on these paper forms will be 
transferred to a password-protected REDCap database such that all data will be stored in the password-protected 
REDCap Database. Only members of the study team will have access to the data. We have no plan to use laptops, jump 
drives, CDs/DVDs to transport data. 
 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
1. 
Data collected for this study will be analyzed and stored. After the study is completed, the de-identified, 
archived data will be transmitted to and stored. 
 
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Principal Investigator 
Evan Graboyes, MD 
Medical University of South Carolina  
135 Rutledge Ave, MSC 550 
Charleston, SC 29425 
843-792-0719 
graboyes@musc.edu 
 
10.1.6 SAFETY OVERSIGHT 
The PI will be responsible for overseeing safety data. Aggregate reviews will occur by the PI for all AEs, UPs, protocol 
violations, audit results, early withdrawals, whether the study accrual pattern warrants continuation/action, and 
endpoint data. Aggregate reviews will occur monthly. 
 
10.1.7 CLINICAL MONITORING 
N/A 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site will perform internal quality management of study conduct, data and biological specimen collection, 
documentation and completion. 
 
Quality control (QC) procedures will be implemented as follows: 
 
Informed consent --- Study staff will review both the documentation of the consenting process as well as a percentage 
of the completed consent documents.  This review will evaluate compliance with GCP, accuracy, and completeness.  
Feedback will be provided to the study team to ensure proper consenting procedures are followed.  
 

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Source documents and the electronic data --- Data will be initially captured on source documents (see Section 10.1.9, 
Data Handling and Record Keeping) and will ultimately be entered into the study database.  To ensure accuracy site 
staff will compare a representative sample of source data against the database, targeting key data points in that review. 
 
Intervention Fidelity — Consistent delivery of the study interventions will be monitored throughout the intervention 
phase of the study. Procedures for ensuring fidelity of intervention delivery are described in Section 6.2.1, 
Interventionist Training and Tracking.  
 
Should independent monitoring become necessary, the PI will provide direct access to all trial related sites, source 
data/documents, and reports for the purpose of monitoring and auditing by the sponsor/funding agency, and inspection 
by local and regulatory authorities. 
 
10.1.9 DATA HANDLING AND RECORD KEEPING  
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection will be the responsibility of the clinical trial staff at the site under the supervision of the site investigator. 
The investigator will be responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data 
reported. All source documents will be completed in a neat, legible manner to ensure accurate interpretation of data. 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for recording data for 
each participant consented/enrolled in the study.  Data recorded in the electronic case report form (eCRF) derived from 
source documents will be consistent with the data recorded on the source documents. 
 
Clinical data (including AEs will be entered into REDCap. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or inaccurate. 
Clinical data will be entered directly from the source documents. 
 
10.1.9.2 STUDY RECORDS RETENTION  
In accordance with Health and Human Services regulation at 45 CFR 46.115(b), we will retain IRB records for at least 
three years. At the end of three years, records will be boxed, labeled, and sent to central storage for another three 
years. Research records will be retained for six years to allow evaluation and repetition by others of the results and to 
investigate an allegation of research misconduct. 
 
 
10.1.10 
PUBLICATION AND DATA SHARING POLICY  
This study will be conducted in accordance with the following publication and data sharing policies and regulations: 
 
NIH Public Access Policy, which ensures that the public has access to the published results of NIH funded research. It 
requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive 
PubMed Central upon acceptance for publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial 
Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be 
registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. In addition, 
every attempt will be made to publish results in peer-reviewed journals.  Data from this study may be requested from 
other researchers x years after the completion of the primary endpoint by contacting <specify person or awardee 
institution, or name of data repository.  Considerations for ensuring confidentiality of these shared data are described in 
Section 10.1.3. 
 

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10.2 ADDITIONAL CONSIDERATIONS 
 
N/A 
 
10.3 ABBREVIATIONS AND SPECIAL TERMS 
 
AA 
African American 
AE 
Adverse Event 
AJCC 
American Joint Committee on Cancer 
BRFSS 
Behavioral Risk Factor Surveillance Survey 
BRP 
Barrier Reduction Plan 
CASE 
Communication & Attitudinal Self-Efficacy 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CRF 
Case Report Form 
CTM-15 
Care Transition Method-15 
DCC 
Data Coordinating Center 
DSMB 
Data Safety Monitoring Board 
eCRF 
Electronic Case Report Forms 
EMR 
Electronic Medical Record 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HBM 
Health Belief Model 
HCC 
Hollings Cancer Center 
HIPAA 
Health Insurance Portability and Accountability Act  
HNC 
Head and Neck Cancer 
ICH 
International Council on Harmonisation  
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IPQ-R 
Illness Perception Questionnaire-Revised 
IRB 
Institutional Review Board 
ISEL-12 
Interpersonal Support Evaluation List-12 
ITT 
Intention-To-Treat 
MDASI-HN 
MD Anderson Symptom Inventory-Head Neck 
MOP 
Manual of Procedures 
MUSC 
Medical University of South Carolina 
NCI 
National Cancer Institute 
NCCN 
National Comprehensive Cancer Network 
NCT 
National Clinical Trial 
NDURE 
Navigation for Disparities and Untimely Radiation thErapy 
NIH  
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
PN 
Patient Navigation 
PORT 
Postoperative Radiation Therapy 
QA 
Quality Assurance 
QC 
Quality Control 
RCT 
Randomized Controlled Trial 
REDCap 
Research Electronic Data Capture 
RT 
Radiation Therapy 
SAE 
Serious Adverse Event 

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SOA 
Schedule of Activities 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

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10.4 PROTOCOL AMENDMENT HISTORY 
 
 
Document 
Date of Issue 
Summary of Change 
Protocol Version 3.0 
31-Jul-2019 
Refined inclusion and exclusion criteria to reflect changes to 8th 
edition AJCC Staging for HPV-related oropharynx carcinoma as well 
screen failure definition; revised screen failure definition and 
efficacy analysis population from ITT to modified ITT 
Protocol Version 2.0 
17-Jun-2019 
Protocol reformatted using the NCI Behavioral Protocol Template. 
In doing so, we refined the study objectives, definitions of 
endpoints, and analytic population. 
Original Protocol 
20-Sept-2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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