A Randomized, Controlled Prospective Trial Evaluating The Impact Of A Nurse Navigation Program on Patients With Gastrointestinal Cancers Undergoing Oncological Treatment
Phase: NA
Conditions: Gastrointestinal Cancer
Sponsor: Wake Forest University Health Sciences

Protocol:  LCI-GI-NOS-NAV-001 
 
 
Version 6: 04/11/2023 
 
 
ACCESS Study 
 
Protocol #:  LCI-GI-NOS-NAV-001 
A Randomized, Controlled ProspeCtive Trial Evaluating The Impact Of A NurSe 
Navigation Program on Patients with GastrointeStinal Cancers Undergoing Oncological 
Treatment  
 
Data Coordinating Center: 
Levine Cancer Institute 
1021 Morehead Medical Drive 
Charlotte NC, 28204 
 
Sponsor-Investigator: 
Mohamed Salem, MD 
Levine Cancer Institute 
1021 Morehead Medical Drive 
Charlotte NC, 28204 
Phone: (704) 355-2000 
Mohamed.Salem@atriumhealth.org 
 
Statistician: 
 Jim Symanowski, PhD  
Levine Cancer Institute  
1021 Morehead Medical Drive, Office 20313  
Charlotte NC 28204  
Phone: (980) 442-2371  
James.Symanowski@atriumhealth.org 
 
Patient Navigation: 
Kris Blackley, RN, MSN, BBA, OCN 
Levine Cancer Institute 
1021 Morehead Medical Drive 
Charlotte, NC 28204 
Phone: (980) 442-3247 
Kris.Blackley@atriumhealth.org 
____________________________________________________________________________ 

 
 
Protocol:  LCI-GI-NOS-NAV-001 
 
 
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The study will be conducted in compliance with the protocol, ICH/GCP and any applicable 
regulatory requirements. 
 
 
 
Throughout this document, symbols indicating proprietary names (®, TM) are not displayed. 
Hence, the appearance of product names without these symbols does not imply that these names 
are not proprietary. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confidential 
The information provided in this document is strictly confidential and is intended solely for the 
guidance of the clinical investigation. Reproduction or disclosure of this document - whether in part 
or in full - to parties not associated with the clinical investigation, or its use for any other purpose, 
without the prior written consent of the Sponsor-Investigator is not permitted. 

 
 
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PROTOCOL SIGNATURE PAGE 
 
PROTOCOL TITLE: A Randomized, Controlled ProspeCtive Trial Evaluating The 
Impact Of A NurSe Navigation Program on Patients with GastrointeStinal Cancers 
Undergoing Oncological Treatment 
 
THE ACCESS TRIAL  
 
 
  
 
The signature below constitutes the approval of this protocol and the attachments and provides 
the necessary assurances that this trial 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 U.S. federal regulations and ICH guidelines. 
 
 
 
 
 
 
 
___________________________________  
_____________________ 
Signature of Investigator 
 
 
            Date 
 
 
MOHAMED SALEM, MD  
Investigator Name (printed) 
 
 

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SYNOPSIS 
TITLE 
A randomized controlled prospective trial evaluating the effectiveness of a nurse navigation 
program for gastrointestinal cancer patients undergoing oncological treatment. 
STUDY POPULATION 
Gastrointestinal cancer patients who are receiving oncologic treatments at LCI. 
SUMMARY OF STUDY 
RATIONALE 
We hypothesize that the prompt and effective coordination of care provided by Oncology Nurse 
Navigation (ONN) service will reduce the number of avoidable, unplanned ED visits and 
hospitalizations, as well as adding measurable value to cancer care, and improve patient overall 
survival. 
STUDY DESIGN  
This trial is designed to evaluate the impact of ONN together with standard care (compared to 
standard of care alone) in terms of clinical outcomes in gastrointestinal cancer patients. 
 
Enrollment of subjects onto this study will not affect the course of their cancer treatment in any 
way; however, we aim to examine if those randomized to ONN will potentially have less utilization 
of acute care services, better experience and improved survival than those receiving standard care 
alone. Subjects will be on the study until the criteria for the final analyses have been met or meet 
any of the other criteria for off study (consent withdrawal, death, etc). Patient overall survival (OS) 
and other patient-related outcomes (listed below) will be assessed. 
 
OBJECTIVES 
Primary Objective:  
The co-primary objectives of this study are to assess the impact of Oncology Nurse Navigation 
service on:  
A) patient acute care utilization (defined as unplanned in-patient admissions, emergency room 
encounters, and/or urgent care visits), and  
B) overall survival (OS) rate at 6 months. 
 
Secondary Objectives:   
Secondary objectives are to compare patients with and without ONN for 
o 
Overall survival  
o 
Rate of OS at 12 months  
o 
Length of hospital stay 
o 
30 days readmission rate 
o 
Referral rate to Palliative Care, Hospice, Nutrition Services, and Social Work Services 
o 
Adherence to clinical care (the number of no-shows as a percent of all scheduled within 
Atrium Health, regardless of visit type) 
o 
Subject satisfaction as assessed by a EORTC IL109 customized questionnaire 
 
KEY INCLUSION 
CRITERIA  
Subjects must meet all of the following applicable inclusion criteria to participate in this study:  
• 
Aged ≥ 18 years at the time of consent, capable of providing written informed 
consent and HIPAA authorization for the release of personal health information.   
• 
Treatment naïve OR adjuvant greater than 6 months ago (except metastatic 
colorectal or small bowel cancer; which may have progressed on or be intolerant 
to fluorouracil/capecitabine, oxaliplatin and irinotecan-based therapy), 
histologically or cytologically confirmed metastatic/recurrent or locally advanced 
GI cancers (metastatic/recurrent fact can be radiologically confirmed) 
• 
Enrollment no later than 30 days after initiation of the systemic therapy 

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• 
Ability of the subject to understand and comply with study procedures for the 
entire length of the study 
• 
Life expectancy is > 3 months 
KEY EXCLUSION 
CRITERIA 
• 
Subjects have previously received or are currently receiving LCI Patient Navigation 
Program services   
• 
Subjects with colorectal cancer enrolled in the Empower Program 
• 
 
• 
Subjects with low grade neuroendocrine tumors 
STATISTICAL 
CONSIDERATIONS 
 
Study is designed with co-primary objectives to evaluate the acute care utilization and 6-month OS 
rate; the study is primarily powered based on the OS landmark objective. The overall type I error 
rate for this study is alpha = 0.05, and the co-primary endpoints were both powered at the 2-sided 
alpha = 0.025 significance level.  It is estimated that treatment with standard therapy results in 
median survival of 8 months, and when assuming an exponential distribution, this corresponds to a 
6-month survival rate of approximately 60%.  The primary OS objective of this study is designed to 
test the null hypothesis that the 6-month OS survival rate is ≤ 60%.  Thus, 300 evaluable subjects, 
randomized in a one-to-one fashion, will provide 80% power, assuming the true 6-month OS rate 
with Nurse Navigation is 80% (a 20% improvement in the 6-month OS rate is considered clinically 
relevant).  This sample size will also provide at least 93% power to detect a 20% reduction in acute 
care visits (assuming there will be 6 acute care utilization visits per year in the control arm).  
 
NUMBER OF SUBJECTS 
 
Up to 347 subjects may need to be enrolled to reach 300 evaluable subjects 
 
 
 

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SCHEMA 
Table 1. 

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GLOSSARY OF TERMS 
 
Abbreviation 
Definition 
COVID-19  
Coronavirus disease 2019  
CTMS 
Clinical Trial Management System 
DMP 
Data Management Plan 
DSMC 
Data Safety Monitoring Committee 
eCRF 
Electronic Case Report Form 
ED 
Emergency Department 
EORTC 
European Organization for Research and Treatment of Cancer  
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEJ 
Gastroesophageal Junction 
GI 
Gastrointestinal 
HIPAA 
Health Insurance Portability and Accountability Act 
ICH 
International Council of Harmonisation 
IRB 
Institutional Review Board 
ITT 
Intent To Treat 
LCI 
Levine Cancer Institute 
LPNP 
LCI Patients Navigation Program 
MDT 
Multidisciplinary Care Team 
NN 
Nurse Navigator 
ONN 
Oncology Nurse Navigation 
OS 
Overall Survival 
OS6 
Overall Survival at 6 months 
QALY 
Quality-adjusted life-year 
SOP 
Standard Operating Procedure 
UAP 
Unanticipated Problems 
 
 

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TABLE OF CONTENTS 
SYNOPSIS ..................................................................................................................................... 4 
SCHEMA ....................................................................................................................................... 6 
GLOSSARY OF TERMS ............................................................................................................. 7 
1. 
BACKGROUND AND RATIONALE ........................................................................ 1110 
1.1 
Background .................................................................................................................... 1110 
1.2 
Study Rationale .............................................................................................................. 1413 
1.3 
Study Design .................................................................................................................. 1514 
2. 
STUDY OBJECTIVES ................................................................................................ 1514 
2.1 
Objectives ....................................................................................................................... 1514 
3. 
SUBJECT SELECTION .............................................................................................. 1615 
3.1 
Subject Identification and Recruitment .......................................................................... 1615 
3.2 
Inclusion Criteria ............................................................................................................ 1615 
3.3 
Exclusion Criteria ........................................................................................................... 1716 
3.4 
Screen Failures ............................................................................................................... 1716 
4. 
SUBJECT ALLOCATION .......................................................................................... 1716 
4.1 
Randomization ................................................................................................................ 1716 
5. 
STUDY PLAN ............................................................................................................... 1817 
5.1 
Study Intervention .......................................................................................................... 1817 
5.2 
Duration of Subject Intervention Status ......................................................................... 1918 
5.3 
Patient satisfaction survey .............................................................................................. 1918 
5.4 
Duration of Data Acquisition ......................................................................................... 1918 
6. 
STUDY CALENDAR ................................................................................................... 2019 
7. 
DETAILS ON STUDY ASSESSMENTS ................................................................... 2120 
7.1 
Screening procedures ..................................................................................................... 2120 
7.2 
During the Intervention .................................................................................................. 2120 
7.3 
Survival Follow-up ......................................................................................................... 2120 
8. 
OFF INTERVENTION AND OFF STUDY .............................................................. 2221 
8.1 
Off Intervention .............................................................................................................. 2221 
8.2 
Off Study ........................................................................................................................ 2221 
8.3 
Special Considerations ................................................................................................... 2221 
9. 
DATA AND SAFETY MONITORING PLANS........................................................ 2221 
10. 
POTENTIAL RISKS/UNANTICIPATED PROBLEMS ......................................... 2322 
10.1 Potential Risks ................................................................................................................ 2322 
10.2 Unanticipated Problems (UAP) ...................................................................................... 2422 
11. 
STATISTICAL CONSIDERATIONS ........................................................................ 2423 
11.1 Milestones ...................................................................................................................... 2423 
11.2 Sample Size .................................................................................................................... 2423 
11.3 Endpoints ........................................................................................................................ 2523 
11.4 Analysis Populations ...................................................................................................... 2726 
11.5 Analysis Methods ........................................................................................................... 2827 

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12. 
STUDY COMPLETION OR TERMINATION ........................................................ 3130 
12.1 Completion ..................................................................................................................... 3130 
12.2 Termination .................................................................................................................... 3130 
13. 
STUDY MANAGEMENT ........................................................................................... 3230 
13.1 IRB Approval ................................................................................................................. 3230 
13.2 Informed Consent ........................................................................................................... 3231 
13.3 Protocol Adherence ........................................................................................................ 3231 
13.4 Other Protocol Deviations .............................................................................................. 3231 
13.5 Retention of Records ...................................................................................................... 3331 
13.6 Ethical and Legal Conduct of the Study ......................................................................... 3331 
13.7 Confidentiality of Records ............................................................................................. 3332 
13.8 Compliance with ClinicalTrials.gov ............................................................................... 3432 
REFERENCES ........................................................................................................................ 3533 
APPENDIX A .......................................................................................................................... 3836 
SYNOPSIS ..................................................................................................................................... 4 
SCHEMA ....................................................................................................................................... 6 
GLOSSARY OF TERMS ............................................................................................................. 7 
2. 
BACKGROUND AND RATIONALE ............................................................................ 10 
1.1 
Background ........................................................................................................................ 10 
1.2 
Study Rationale .................................................................................................................. 13 
1.3 
Study Design ...................................................................................................................... 14 
3. 
STUDY OBJECTIVES .................................................................................................... 14 
2.1 
Objectives ........................................................................................................................... 14 
4. 
SUBJECT SELECTION .................................................................................................. 15 
3.1 
Subject Identification and Recruitment .............................................................................. 15 
3.2 
Inclusion Criteria ................................................................................................................ 15 
3.3 
Exclusion Criteria ............................................................................................................... 16 
3.4 
Screen Failures ................................................................................................................... 16 
5. 
SUBJECT ALLOCATION .............................................................................................. 16 
4.1 
Randomization .................................................................................................................... 16 
6. 
STUDY PLAN ................................................................................................................... 17 
5.1 
Study Intervention .............................................................................................................. 17 
5.2 
Duration of Subject Intervention Status ............................................................................. 17 
5.3 
Patient satisfaction survey .................................................................................................. 18 
5.4 
Duration of Data Acquisition ............................................................................................. 18 
7. 
STUDY CALENDAR ....................................................................................................... 19 
8. 
DETAILS ON STUDY ASSESSMENTS ....................................................................... 20 
7.1 
Screening procedures ......................................................................................................... 20 
7.2 
During the Intervention ...................................................................................................... 20 
7.3 
Survival Follow-up ............................................................................................................. 20 
9. 
OFF INTERVENTION AND OFF STUDY .................................................................. 21 
8.1 
Off Intervention .................................................................................................................. 21 

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8.2 
Off Study ............................................................................................................................ 21 
8.3 
Special Considerations ....................................................................................................... 21 
10. 
DATA AND SAFETY MONITORING PLANS............................................................ 21 
11. 
POTENTIAL RISKS/UNANTICIPATED PROBLEMS ............................................. 22 
10.1 Potential Risks .................................................................................................................... 22 
10.2 Unanticipated Problems (UAP) .......................................................................................... 23 
12. 
STATISTICAL CONSIDERATIONS ............................................................................ 23 
11.1 Milestones .......................................................................................................................... 23 
11.2 Sample Size ........................................................................................................................ 23 
11.3 Endpoints ............................................................................................................................ 24 
11.4 Analysis Populations .......................................................................................................... 26 
11.5 Analysis Methods ............................................................................................................... 27 
13. 
STUDY COMPLETION OR TERMINATION ............................................................ 30 
12.1 Completion ......................................................................................................................... 30 
12.2 Termination ........................................................................................................................ 30 
14. 
STUDY MANAGEMENT ............................................................................................... 30 
13.1 IRB Approval ..................................................................................................................... 30 
13.2 Informed Consent ............................................................................................................... 31 
13.3 Protocol Adherence ............................................................................................................ 31 
13.4 Other Protocol Deviations .................................................................................................. 31 
13.5 Retention of Records .......................................................................................................... 32 
13.6 Ethical and Legal Conduct of the Study ............................................................................. 32 
13.7 Confidentiality of Records ................................................................................................. 32 
13.8 Compliance with ClinicalTrials.gov ................................................................................... 32 
REFERENCES ............................................................................................................................ 33 
APPENDIX A .............................................................................................................................. 36 
APPENDIX B ............................................................................................................................... 40 
 
 

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1. BACKGROUND AND RATIONALE 
1.1 Background 
1.1.1 
Multidisciplinary Cancer Care  
In 2019, an estimated 1,762,450 new cancer cases will be diagnosed in the United States and 606,880 
people will die from the disease (1), having a major impact on society in the United States and across 
the world.  
 
The diagnosis and treatment of cancer is a complex process that requires many different clinical 
specialists to collaborate over a prolonged period. The multidisciplinary care team (MDT) model has 
become the standard approach for cancer care delivery. The introduction of MDTs has improved 
survival (2) and reduced the variability in survival rates between hospitals (3). When an MDT functions 
efficiently, patients are referred for appropriate medical interventions in a timely manner, individual 
patient needs are more likely to be met, and care is coordinated (4-6). Uncoordinated care can 
significantly hinder effective cancer care delivery; it is associated with poor symptom management (7), 
medication errors (8), missed follow-up diagnostic tests (9), and delays in the initiation of therapy. 
Coordination of care is particularly important for patients with poor prognosis to ensure that they are 
treated in a timely manner, their symptoms are well managed, and necessary interventions are provided 
on time. 
1.1.2 
Management Of Gastrointestinal Cancers 
Gastrointestinal cancer patients are very complex to treat, with specific prognosis (10, 11). The 5-year 
relative survival rates for stage IV disease – 3% for pancreatic cancer, 5-10% for gastroesophageal 
cancer and 14% for colorectal cancer – are among the lowest of all cancer types (12). Pancreatic cancer 
is the fourth most common cause of cancer death. The only potentially curative intervention, surgical 
resection, is not an option for most patients because most are diagnosed at a late stage due to paucity of 
early symptoms. Likewise, surgery is the only curative option for other gastrointestinal cancer, and 
because of the vague nature of early symptoms of disease, many patients are diagnosed at a late stage. 
Therefore, prolonging life and maximizing the quality of life are the main treatment goals for most 
patients with these diagnoses. A large MDT is typically needed to provide optimal treatment and care 
for these patients, which ideally comprises gastroenterologists, oncologists, radiologists, radiation 
oncologists, specialized surgeons, nutritionists, palliative care clinicians, social workers, and many 
others.  The sheer volume of providers required makes the coordination of effective care for these 
patients extremely challenging; however, this essential coordination is the pivotal point of the highest 
quality of care for these patients. 
1.1.3 
Healthcare Disparities 
In an ideal situation, all patients would receive an equally high level of quality cancer care, but 
healthcare disparities exist between privileged and under-resourced patient populations. Social 
variables such as income level, racial and ethnic background, and insurance status affect access to care 
and the quality of cancer care received by patients (13-15). These disparities affect almost every aspect 

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of the cancer care experience. Several studies showed that sociodemographic variables influence the 
likelihood of experiencing a delay in the initiation of adjuvant chemotherapy for breast cancer (16), a 
delay in the time from diagnosis to treatment initiation for head and neck cancers (17) and advanced 
bladder cancers (18), and surgery wait times for many cancer types (19). In a study of early-stage 
pancreatic cancer patients, sociodemographic variables appeared to determine how likely a patient was 
to undergo tumor resection, and geographic location was independently associated with disease-specific 
survival after resection (20). In a study of gastric cancer patients, racial background was found to 
influence treatment decisions and survival rates (21).  
1.1.4 
Acute Care Utilization 
Certain populations are more likely than others to use acute care services for cancer-related symptoms. 
A 2018 study showed that pancreatic and gastric cancer patients were more likely than not to be 
frequent emergency department (ED) attenders (22). In addition, a study of advanced cancer patients 
showed that those who missed their first appointment were more likely than patients who kept their 
appointment to have an ED visit within two weeks of the missed appointment (23). These studies 
suggest that certain patient groups especially need additional support to ensure that they get appropriate 
care when they need it, outside of the acute care setting. Initiatives to enhance care coordination and 
easy access to care may help to keep patients out of the ED, improve the quality of cancer care, and 
alleviate the high economic burden of ED attendance and frequent hospitalization on the healthcare 
system. 
1.1.5 
Strategies to Improve Care Coordination 
The MDT model improved the quality of cancer care even though coordinating care for all patients 
within this model is challenging. Several strategies have been applied in an effort to improve care 
coordination. For instance, a centralized phone call reminder system in 10 clinics at a Houston-based 
hospital reduced the number of missed appointments (24). Conversely, a complementary ride sharing 
program in Philadelphia did not reduce rates of missed primary care appointments (25). In a 2018 
review, Handley and colleagues outlined several approaches to reduce acute care utilization among 
cancer patients. Strategies included increasing early access to palliative care, creating standardized 
approaches to symptom management, and enhancing care coordination through programs such as 
patient navigation (26). Improving the coordination of care for vulnerable patient populations is critical 
for reducing healthcare disparities and maximizing the quality of life for patients with a poor prognosis.  
1.1.6 
Patient Navigation Program 
There is a large body of evidence to support the positive impact of patient navigation on many aspects 
of cancer care delivery. Patient navigation was first introduced in 1990, in New York, to address the 
disparities in breast cancer survival for minority populations (27). Since then, oncology patient 
navigation has expanded to many healthcare systems, and this patient-centered service was introduced 
as a new standard by the Commission on Cancer in 2015  with the hope of remedying the apparent 
inequality in cancer care (28). Patient navigation programs aim to identify and address individual 
barriers to care. The scope of work varies widely between different patient navigation programs, most 
notably by the type of navigators employed, which included lay navigators, social workers, or nurse 

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navigators. In the oncology setting, experienced registered nurses that carry out patient navigation 
programs are often referred to as Oncology Nurse Navigators, and the program involving these 
experienced, registered oncology nurse navigators is termed Oncology Nurse Navigation (ONN). Nurse 
navigators serve to provide supportive and coordinated care; they bridge the gap between clinical 
providers in MDTs and patients and ensure that patients have the resources they need to complete the 
recommended series and courses of treatment. In other words, the role of a nurse navigator is to support 
patients as they go through the many stages of their cancer journey. 
 
Many studies demonstrate that patient navigation increases cancer screening (29-31) and shortens the 
time to treatment initiation (32-38).  
 
A few studies have addressed the impact of navigation programs on different aspects of cancer care 
beyond treatment initiation. A secondary analysis of geriatric cancer patients within The University of 
Alabama at Birmingham Health System Cancer Community Network showed that patients in a lay 
navigator program had fewer hospitalizations and ED admissions than a matched cohort; moreover, this 
reduction in resource utilization translated into a sharp decline in treatment costs (39). A nurse 
navigation program for oncology pain management at two German hospitals improved adherence to 
pain medication, reduced pain, and increased quality of life (40). Furthermore, to test the hypothesis 
that navigation increases access to palliative care services for Latino adults with advanced cancer, a 
randomized clinical trial was conducted across multiple healthcare facilities in Colorado. Researchers 
found that navigation increased advance care planning and improved physical symptoms (41).  
1.1.7 
Oncology Nurse Navigation at Levine Cancer Institute 
A nurse navigation program was introduced at Levine Cancer Institute (LCI) in 2011. LCI Patients 
Navigation Program (LPNP) has expanded to all 28 LCI locations and currently employs approximately 
40 Oncology Nurse Navigators – registered nurses with a BSN and two or more years of nursing 
experience, preferably in oncology. LPNP stops active navigation at the time the patient completes 
active treatment and transitions into survivorship. Metastatic/recurrent or advanced, unresectable 
patients are navigated through end of their life.  
 
To assess the potential impact of nurse navigation on clinical outcomes at LCI, several retrospective 
observational studies were conducted. Patients diagnosed with one of eight cancer types associated with 
a poor prognosis (acute myeloid leukemia, esophagus, liver, lung, myeloma, ovary, pancreas, stomach), 
who were assigned oncology nurse navigators were compared to a matched cohort who were not 
assigned navigators. Navigated patients had improved overall survival (OS). The strongest survival 
benefit was observed for patients insured by Medicaid, which suggests that the nurse navigation 
program may reduce disparities in cancer care(42). The impact of nurse navigation on acute care 
utilization was investigated in a separate cohort of patients, each with an advanced-stage cancer 
including bladder, breast, colon, kidney, lung, pancreas, prostate, thyroid, or uterine cancer or 
melanoma. Acute care utilization was significantly reduced for navigated patients compared to those 
who were not navigated (43).  

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1.1.8 
The Role of Oncology Nurse Navigators at LCI 
Oncology Nurse Navigators are usually “tumor site-specific”. At LCI GI clinics, they are currently 
employed to care exclusively for patients with gastrointestinal cancers (GI NN). Regional sites with 
lower volumes have General Nurse Navigators working with all types of cancers (General NN). 
 
Oncology Nurse Navigators at LCI play many roles such as: 
1. Care Coordinator. This encompasses expediting care and facilitating communication between 
providers, the patient, and the family. LCI Navigators communicate across treatment modalities 
and expedite referrals. They oversee the coordination of appointments and ensure that they are 
made in a timely manner. 
2. Patient-centered assessor of barriers to care. This includes assisting patients in overcoming the 
challenges encountered throughout their treatment. These barriers can be logistical, health 
literacy-related, psychosocial, financial, transportation-related, etc.  
3. Patient educator. This involves communicating with the patient to ensure that they understand 
their disease, their care plan, their treatment, and how to manage their symptoms and treatment 
side-effects. 
4. Patient referral specialist. Referral of patients to appropriate resources helps the patients to 
overcome identified barriers related to finances, treatment logistics, psychosocial health, 
transportation, and health literacy, for example. These resources may be within the healthcare 
system or the community. 
5. Patient advocate. Navigators serve as patient advocates and provide a central point of contact 
for the patient as issues and concerns related to their care arise. 
 
Navigation begins at the time of diagnosis and continues throughout active treatment. LCI navigation 
has a standardized patient intake process and all new patients that are referred for navigation are 
promptly assessed to identify any potential barriers to care. Navigators assess each patient’s needs, 
either in person at the patient’s first visit or over the telephone. On the basis of this assessment, 
navigators assign each patient an acuity score that grades the level of support needed. With this grading 
system, Oncology Nurse Navigators can prioritize patient needs and assist with resource management 
at an administrative level. Patient assessments are repeated and reevaluated throughout treatment. All 
assessments are documented in the patient’s Electronic Medical Record using Patient Navigation 
Acuity Grading Scale (See Appendix A). 
1.2 Study Rationale 
As discussed above, our preliminary results from retrospective analyses demonstrated the potential 
impact of our nurse navigation program on survival, enhancement of care coordination and quality of 
care (43).  Furthermore, navigated patients were shown to have improved overall survival (OS) 
compared to those who were not navigated (42). Consistently, these data are supported from studies in 
other centers as well (29-31). 
 
However, it remains unclear whether the improved outcomes are a result of nurse navigation program 
or case selection bias, notwithstanding the propensity matching of our previous study. To this end, we 
propose a prospective, randomized controlled trial to formally examine the effectiveness of nurse 
navigation on cancer patients undergoing oncological treatment. This study particularly aims 

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prospectively to assess the impact of ONN on acute care utilization and clinical outcomes. This study is 
critical to rationalize the continued fiscal support of nurse navigation programs in oncology and is 
likely to affect health care policy and reimbursement strategies if a positive outcome is proven for nurse 
navigation.  It is not our intention to address the differences between nurse navigation and non-nurse 
navigation.  
1.3 Study Design 
In this study, we plan to recruit 300 patients with gastrointestinal cancers, who are receiving care at 
LCI. Upon accrual, patients will be randomized 1:1 to receive standard of care plus ONN service (n = 
150) or standard of care only (without ONN service; n = 150). Patients in both arms will be assessed for 
acute care utilization and overall survival (OS) rate at 6 months as primary objectives. 
 
Anticipated accrual period will be 48 months. 
 
We hypothesize that the implementation of a prompt and effective coordination of care provided by 
ONN will reduce the number of avoidable, unplanned ED visits and hospitalizations, reliance on acute 
care utilization, and may result in an improvement of patient overall survival.  
2. STUDY OBJECTIVES 
2.1 Objectives 
2.1.1 
Primary Objective 
• The co-primary objectives of this study are to examine the impact of Oncology Nurse 
Navigation program on patient Acute Care Utilization, defined as unplanned inpatient 
admissions, emergency room encounters, and/or urgent care visits, and overall survival rate at 
6 months. 
2.1.2 
Secondary Objectives 
• Secondary objectives are to compare patients with and without ONN for 
o Overall survival 
o Overall survival rate at 12 months 
o Length of hospital stay 
o Time from hospice referral to death 
o 30 days readmission rate 
o Referral rate to Palliative Care, Hospice, Nutrition Services, and Social Work Services  
o Adherence to clinical care (the number of no-shows as a percent of all scheduled within 
Atrium Health, regardless of visit type) 
o Subject satisfaction as assessed by a EORTC IL109 customized questionnaire 
2.1.3 
Exploratory objectives 
• To compare outcomes within the ONN arm for subjects navigated by GI specialists versus 
subjects navigated by general oncology nurse navigators. 

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• To describe the distribution of the timing from enrollment to initiation of systemic therapy. 
• To evaluate outcomes within the ONN arm as a function of the time from enrollment to 
initiation of systemic therapy in those evaluable subjects initiating systemic therapy on 
study.   
3. SUBJECT SELECTION 
3.1 Subject Identification and Recruitment 
 Subjects will be recruited at LCI sites where ONN performed under the LCI Patient Navigation 
Program is available. Patients with the diagnosis of GI cancers (as defined in the inclusion criteria) who 
are not previously or currently receiving navigation service in LCI will be identified and enrolled into 
the study. Patients will not be excluded from recruitment based on their gender, race, or ethnic origin.  
3.2 Inclusion Criteria 
Patients Subjects must meet all the following applicable inclusion criteria to participate in this study:  
1. Capable of providing written Iinformed consent and HIPAA authorization for the release of 
personal health information 
2. Aged ≥ 18 years at the time of consent 
3. Subject is planning to receive their cancer care at LCI at the time of consent 
4. Histologically or cytologically confirmed one of the following diagnoses (metastatic/recurrent 
status can be radiologically confirmed): 
a. Treatment naïve* or adjuvant greater than 6 months ago: 
i. Metastatic/recurrent or locally advanced, unresectable or borderline resectable 
(as defined per NCCN, Alliance or other acceptable guidelines criteria) 
pancreatic cancer  
ii. Metastatic/recurrent or locally advanced, unresectable esophageal, 
gastroesophageal junction (GEJ) or gastric cancer patients or those who are not 
eligible for surgery 
iii. Metastatic/recurrent or locally advanced, unresectable hepatocellular carcinoma 
(HCC) 
• radiographic confirmation of the HCC diagnoses is acceptable 
• prior locoregional treatment for subjects with HCC is allowed, but no prior 
systemic therapy is allowed 
iv. Metastatic/recurrent or locally advanced, unresectable biliary cancers (e.g. gall 
bladder cancer, cholangiocarcinoma) 
• prior locoregional treatment for subjects with biliary cancers is allowed, but 
no prior systemic therapy is allowed 
b. Disease progression on or are intolerant to fluorouracil/capecitabine, oxaliplatin, and 
irinotecan-based therapy (e.g. FOLFOX, FOLFIRI, or FOLFOXIRI) 
i. Metastatic colorectal or small bowel cancer  
*Subjects can be enrolled within, but no later than 30 days after initiation of their systemic 
therapy, however every effort will be made to enroll subjects prior to the initiation of 

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systemic therapy. Subjects who have completed or undergoing a current palliative 
radiotherapy are allowed 
5. Ability to read and understand the English or Spanish language 
5.6.As determined by the enrolling physician, ability of the subject to understand and comply with 
study procedures for the entire length of the study. However, refusal to complete a patient 
satisfaction questionnaire IL109 should not refrain a subject from being enrolled.  
6.7.Life expectancy is >3 months 
3.3 Exclusion Criteria 
Subjects meeting any of the criteria below may not participate in the study: 
1. Subjects have previously received or are currently receiving LCI Patient Navigation Program 
services  
1.2.Subjects with colorectal cancer enrolled in the Empower Program 
2.3.Subjects with low grade neuroendocrine tumors 
3.4 Screen Failures 
A consented subject who, for any reason (e.g., fails to satisfy the eligibility criteria or withdraws 
consent for study participation), terminates his/her study participation prior to randomization is 
regarded as a “screen failure.” All screen failures will be tracked. Reasons (e.g. specific 
inclusion/exclusion criteria) for screen failure will be recorded in the CTMS. 
4. SUBJECT ALLOCATION  
4.1 Randomization 
Following informed consent and eligibility check per standard operating procedures, subjects will be 
randomized in a 1:1 fashion to either Arm A (standard of care plus ONN service) or Arm B (standard 
of care only) and assigned a Sequence Number. This will be accomplished utilizing the CTMS whereby 
a list of Sequence Numbers and associated treatment arm assignments randomly generated prior to 
study activation will be uploaded by a member of the Levine Cancer Institute Data Coordinating 
Center.  The Sequence Number will be a four digit randomly generated ID number, ranging from 0001 
to 9999.  A stratified block randomization will be utilized including the following stratification factors 
to reduce confounding of comparisons between the treatment arms: 
 
• COVID-19 study period: 
o Time from study activation to end of pandemic* (Study Period A) 
o End of pandemic to end of study (Study Period B) 
o Note: The time of the start of the post-pandemic era will be determined by a declaration 
from World Health Organization, Center for Disease Control (or other United States 
federal agency), or LCI, whichever comes first.  
 
*On January 30, 2023, the Biden Administration announced its plan to end the COVID-
19 national emergency and public health emergency in the United States on May 11, 

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2023. The end of the pandemic will be defined by the United States declaration of the 
end of the COVID-19 national emergency and public health emergency.  
 
• Disease diagnosis: 
o Metastatic pancreatic 
o Locally advanced unresectable pancreatic 
o Metastatic or unresectable esophageal, gastroesophageal junction (GEJ) or gastric 
cancers 
o Metastatic or unresectable hepatocellular carcinoma 
o Metastatic or unresectable biliary cancer 
o Colorectal cancer patients who had disease progression on or are intolerance to 
fluorouracil, oxaliplatin, and irinotecan-based therapy 
5. STUDY PLAN 
See Schema (Table 1). 
 
This trial is designed to evaluate the impact of ONN in addition to standard care (compared to standard 
care alone without ONN) on GI cancer patients’ acute care utilization as well as clinical outcomes.  
Subjects enrolled to this study will be patients presenting to the GI clinic. 
    
Enrollment of patients onto this study will not affect the course of their cancer treatment in any way; 
however, we hypothesize that those randomized to ONN will have less utilization of acute care and an 
improved survival compared to those receiving standard care only.  
 
Target accrual period is anticipated to be 48 months. 
5.1 Study Intervention 
The study intervention is providing the patient with the service of navigation (ONN) performed under 
LCI Patient Navigation Program (LPNP), led by a registered oncology nurse. When the patient is 
diagnosed with cancer, and after successfully enrolled on the study, subject(s) who are randomized to 
the ONN will be assigned an ONN. Subjects can be enrolled within, but no later than, 30 days after 
initiation of their systemic therapy, however every effort will be made to enroll subjects prior to the 
initiation of systemic therapy. This ONN`s first role will be to assess the subject’s needs either in 
person at the subject’s first visit, over the telephone or utilizing virtual care. The subsequent services 
may be continued the same way. 
 
 
The ONN will aim to perform the following: expedite care, facilitate communication between the 
subject and providers, assist the subject in overcoming challenges throughout their treatment, ensure 
the subject understands their care plan, disease, and treatment, and most importantly, serve as the 
subject’s central point of contact when questions or concerns arise.  
 

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For subject randomized for the control arm intervention will be defined as data collection only, per 
section 5.43. 
5.2 Duration of Subject Intervention Status 
Subject on intervention status will begin on the day of randomization and continue until criteria for off-
intervention is met (Section 8.1).  
5.3 Patient satisfaction survey 
Patient satisfaction will be assessed through EORTC IL109 customized questionnaire. Subjects will be 
offered the option to provide patient satisfaction survey responses electronically or during a clinic visit. 
Completion of EORTC IL109 questionnaire can be declined by a subject at any time-point. Refusal to 
complete a survey will not be a protocol deviation or refrain a subject from being enrolled, and will 
NOT be a criterion for study discontinuation by the Investigator. If subject is not able to complete a 
survey during the study window, they will be asked to complete at the next scheduled in-person visit. 
This will NOT be considered as a protocol deviation.  
5.4 Duration of Data Acquisition  
Underlying primary data needed to support study endpoints will be acquired by trained study conduct 
research staff.  For each subject, this will be done starting at the day of randomization and then on an 
every 3-month basis.  
 
The duration of data acquisition will be as follows: 
• For ACU, readmissions, adherence to clinical care, and subject satisfaction, the duration of data 
acquisition will be until the subject meets the criteria for off-intervention (see Section 8.1) 
• For survival data, the duration of data acquisition will be until the subject becomes off study 
(see Section 8.2). 
 

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6. STUDY CALENDAR 
Table 2. Study Procedures and assessments 
 
 Study Procedures 
 
Registration 
Baseline2 
 
 
During the 
Intervention8  
 
Off-
intervention9   
 
Survival 
Follow-up 
Informed Consent 
X 
 
 
 
 
Demographics1 
 
X 
 
 
 
Medical History3 
 
X 
 
 
 
Adherence to clinical 
care4   
 
 
 
 
 
Continuously throughout the study 
from Randomization to  
Off-intervention every 3 months11 
 
Acute Care Utilization5 
 
 
 
Collection of subject`s 
hospital admission and 
discharge dates6 
 
 
 
Survival assessment  
 
 
X10 
Subject satisfaction 
survey 
 
 
X7 
X7 
 
 
 
Key to Footnotes  
1 Demographic information will include: DOB, sex, race, live-in caregiver status, income, insurance status, education level, zip code. 
2 Screening window is at most 28 days prior to enrollment. 
3 The following baseline medical history information will be manually collected from EMR: smoker status, diabetes, ETOH use, BMI, weight, 
clinically significant pre-existing conditions, and treatment and procedure history. 
4 Collect the number of visits scheduled for the subject and the number of no-shows, to include all visits scheduled within Atrium Health, not 
just oncology related. 
5 Collect unplanned inpatient hospital admissions, emergency room encounters, and urgent care visits. 
6 Hospitalization encounter is temporally defined as a difference between date of discharge and subtracted date of admission. 
7 Assessed by a EORTC IL109 customized questionnaire (Appendix B). It will be collected in two time points. 1st survey will be collected at 
4 weeks +2 weeks after the randomization, 2nd survey at 10-14 weeks from the randomization. Subjects will be offered the option to provide 
survey responses electronically or during a clinic visit. If subject is not able to complete a survey during the study window, they will be asked 
to complete at the next scheduled in-person visit. This will NOT be considered as a protocol deviation.  
8 If subject remains on study after the relocation from one LCI site to another LCI site, subject will remain on their original arm he/she was 
randomized to. 
9 Subject will become off-intervention and enter the survival follow-up after meeting the criteria for off-intervention, Section 8.1. 
10 Survival will be continuously assessed for subjects who are On Intervention (at least every 3 months ± 2 weeks ). For subjects who are Off 
Intervention, best effort will be made to obtain survival information approximately every 6 months ±4 weeks either by phone or during a 
clinic visit   until the off-study criteria are met (Section 8.2). 
11 Research designee will contact the subject by phone every 3 months ± 2 weeks, or during a clinic visit. 

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7. DETAILS ON STUDY ASSESSMENTS  
Please also refer to the Study Calendar (Table 2 in Section 6.) 
7.1 Screening procedures 
Prior to enrollment, subjects will undergo standard screening procedures to confirm whether the subject 
meets eligibility criteria: 
 
• Informed Consent: No protocol-related assessments may be performed prior to obtaining 
informed consent.  
• Medical History: A complete relevant medical history should be obtained, including: smoker 
status, diabetes, ETOH use, BMI, weight, clinically significant pre-existing conditions, and 
treatment and procedure history. 
• Subject demographics (DOB, sex, race, live-in caregiver status, income, insurance status, 
education, zip code) should be recorded. 
7.2 During the Intervention 
• Subject satisfaction survey: a EORTC IL109 customized questionnaire (Appendix B) will be 
collected at two time points.  
1st survey at 4 weeks +2 weeks after the randomization,  
2nd survey at 10-14 weeks from randomization. Patients will be provided with the option to 
provide survey responses electronically or during a clinic visit. 
 
The following assessments will be performed throughout the study from the Randomization to Off-intervention 
every 3 months: 
 
• Acute Care Utilization: unplanned inpatient admissions, emergency room encounters, and 
urgent care visits should be collected continuously throughout the study from the 
randomization. 
Hospital admission and discharge dates should be tracked. 
• Adherence to clinical care: Collect the number of visits scheduled for the subject and the 
number of no-shows, to include all visits scheduled within Atrium Health, not just oncology 
related, continuously throughout the study from the randomization. 
• Survival assessment: Subjects will be assessed during the ONN services continuously 
throughout the study from the randomization. 
7.3 Survival Follow-up 
• 
Survival assessment:  The best effort will be made to obtain survival information after the 
subject comes off-intervention until the off-study criteria are met (Section 8.2). 

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8. OFF INTERVENTION AND OFF STUDY  
8.1 Off Intervention 
Subjects will be removed from Intervention Status when at least one of the following criteria are met: 
• Subject on either arm who permanently discontinues all active anti-cancer therapy 
• Subject on either arm who relocates to a non-LCI institution 
• Subject on either arm who relocates to an LCI site without LPNP  
• Subjects randomized to the ONN arm withdraws consent to participate in the LPNP 
8.2 Off Study 
Subjects may stop their participation in this study at any time if they no longer wish to participate, or if 
the investigator believes this to be in the best interest of the subject.  
 
When subjects are removed from the study, the reason for study removal and date the subject was 
removed should be documented.  
 
Subjects will remain on study until the criteria for final analysis have been met (Section 11.5). 
Reasons a subject may be removed from study prior to meeting the criteria for final analysis include, 
but are not limited to: 
• The subject or legal representative (such as a parent or legal guardian) withdraws study consent 
or study participation  
• Study is terminated early (Section 12) 
• Investigator’s decision to withdraw the subject 
• Subject death 
 
Subjects that are Off Study will not participate in any study related procedures, including data 
collection.  The completion of this study is not related to the continuance of cancer care. 
8.3 Special Considerations 
Subject Relocation: At any point during the conduct of the trial, the subject may desire to relocate from 
their present LCI study site to another LCI facility with LPNP due to travel feasibility or other 
circumstances. If subject relocates away from the study site, the present study site Sub-Investigator will 
consult with relocation-site Sub-Investigator to determine if subject should continue study participation.  
If subject remains on study, subject will remain on their original arm he/she was randomized to. 
9. DATA AND SAFETY MONITORING PLANS 
Data will be collected in electronic case report forms (eCRFs). The database uses fully validated secure 
web-enabled software that conforms with 21CFR Part 11 requirements. Study personnel will be trained 
on data entry by the sponsor and provided protocol-specific eCRF guidelines. 
 
This protocol will be monitored according to the processes in effect for all LCI investigator-initiated 
studies and the protocol-specific monitoring plan, the protocol-specific Data Management Plan (DMP) 

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and will abide by applicable regulations and guidelines (e.g. Good Clinical Practice [GCP]).  It is the 
responsibility of the Sponsor-Investigator to monitor the  studysafety data for this study.  The Sponsor-
Investigator and other sponsor-level team members will meet regularly to monitor subject consents, 
enrollment and retention, studyafety data, and timeliness/validity/integrity of the data. Documentation 
of these meetings will be kept with study records. The Sponsor-Investigator will submit reports to the 
LCI Data and Safety Monitoring Committee according to the institutional Data and Safety Monitoring 
Plan. 
 
This study will be monitored to ensure the study is conducted in compliance with the study protocol, 
SOPs of the LCI and Atrium Health Office of Clinical and Translational Research (and/or other 
participating institutional SOPs), the FDA, and other applicable regulations and guidelines (e.g. GCP).  
 
Investigators and/or their delegated study personnel will be required to be available during the 
monitoring visits. 
10. POTENTIAL RISKS/UNANTICIPATED PROBLEMS  
10.1 
Potential Risks 
10.1.1 Subject Confidentiality 
We do not anticipate any breach of confidentiality as no records will be shared with any personnel 
outside the research team.  All medical information including assessments and other medical records 
will be recorded and stored in a database. The database will exist on a password protected secured 
server. Medical records data will be abstracted by the Research Designee. All records will be kept 
confidential.  
 
All data and records generated during this study will be kept confidential in accordance with 
Institutional policies on subject privacy and HIPAA; the investigators and other site personnel will not 
use such data and records for any purpose other than conducting the study. No breach of confidentiality 
is anticipated because no records will be shared with any personnel outside the research team. All 
medical information including assessments and other medical records will be recorded and stored in a 
database. The database will exist on a password protected secured server. All records will be kept 
confidential. 
 
To minimize risks to confidentiality, data will only be monitored by Sponsor-Investigator and trained 
research staff. At a minimum, research staff will have completed basic human subject protection 
research training. 
10.1.2 Emotional Distress 
Some questions in the questionnaires could create emotional distress or confusion.  If a subject 
experiences distress or confusion, the questionnaire process will be interrupted or discontinued, and the 
Research Designee will follow up with the Sponsor-Investigator. 

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10.2 
Unanticipated Problems (UAP) 
10.2.1 Definition 
A UAP is any incidence, experience or outcome that is unexpected (e.g., a lost or stolen laptop 
computer that contains sensitive study information) given the information provided in research-related 
documentation (e.g., informed consent) and the study population characteristics, that is related or 
possibly related to participation in the research study and places the participant at an increased risk.  
10.2.2 Reporting 
All UAPs occurring during the conduct of a protocol and meeting the definition of a UAP will be 
reported to the Sponsor-Investigator and IRB per IRB reporting requirements.  
11. STATISTICAL CONSIDERATIONS 
11.1 
Milestones  
11.1.1 Registration Date 
The date the subject signs the informed consent. 
11.1.2 Enrollment Date 
The date that the subject is randomized.  
11.1.3 Intervention Discontinuation Date 
The date when S-I becomes aware of the subject meeting any of the criteria in Section 8.1. 
11.1.4 Off Study Date 
The date the subject terminates participation on the study or is removed from the study per the criteria 
in Section 8.2. 
11.2 
Sample Size 
This study is designed with co-primary objectives to evaluate the acute care utilization and 6-month OS 
rate.  Power and sample size calculations were primarily calculated based on the OS landmark 
objective.  The overall type I error rate for this study is alpha = 0.05.  Therefore, the co-primary 
endpoints were both powered at the 2-sided alpha = 0.025 significance level.  We estimate that 
treatment with standard therapy results in median survival of 8 months.  Assuming an exponential 
distribution, this corresponds to a 6-month survival rate of approximately 60%.  Therefore, the primary 
OS objective of this study is designed to test the null hypothesis that the 6-month OS survival rate is ≤ 
60%.  A total of 300 evaluable subjects enrolled in a one-to-one fashion will provide 80% power, 
assuming the true 6-month OS rate with Nurse Navigation is 80%.  A total of 347 subjects may need to 
be enrolled to achieve 300 evaluable subjects. A 20% improvement in the 6-month OS rate is 
considered clinically relevant.  This sample size will also provide at least 93% power to detect a 20% 
reduction in acute care visits (assuming there will be 6 acute care utilization visits per year in the 
control arm).  

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11.3 
Endpoints 
11.3.1 Definition of Primary Endpoints 
Overall survival at 6 months (OS6) will be determined as a binary variable indicating whether or not 
the subject was alive at 6 months following randomization.  
 
Acute care utilization visits will be calculated for each subject as the total number of acute care visits 
normalized to an annual basis. Acute care visits will include unplanned hospital admissions, ED visits, 
and urgent care visits.  
11.3.2 Definition of Secondary Endpoints 
• Overall Survival (OS) 
OS is defined as the duration from enrollment to the study (randomization) to the date of death from 
any cause.  Subjects who are alive or lost to follow-up at the time of the analysis will be censored at 
the last known date they were alive. 
 
• Overall survival at 12 months (OS12) will be determined as a binary variable indicating whether 
or not the subject was alive at 12 months following randomization.  
 
• Length of hospital stay (LOS) 
Length of stay will be calculated for each subject and for each unplanned in-patient admission as 
the difference between the admission date and the discharge date (plus 1).  
 
• Time from hospice referral to death 
Time from hospice referral to death is defined as the duration from hospice referral to the date of 
death from any cause.  Subjects who are alive or lost to follow-up at the time of the analysis will be 
censored at the last known date they were alive. This endpoint will only be calculated for subjects 
referred to hospice. 
 
• 30-day readmission 
The 30-day readmissions will be calculated for each subject as the total number 30-day readmissions.  
This endpoint will only be calculated for subjects with at least one in-patient admission.   
  
• Referral to Supportive Oncology services 
Referral to Supportive Oncology will be binary variables determined for each subject indicating 
whether or not the patient received referrals to Palliative Care, Nutrition Services, and Social Work 
Services offered by the Levine Cancer Institute Department of Supportive Oncology.  
 
• Adherence to clinical care   
Adherence to clinical care will be calculated for each subject in terms of the rate of subject 
compliance with scheduled visits.  For each subject, the number of no-shows will be calculated as a 
percent of all scheduled within Atrium Health visits, regardless of visit type.   

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• Patient satisfaction 
Patient satisfaction will be assessed through the EORTC IL109 customized questionnaire.  The 
EORTC IL109 customized questionnaire was compiled in the EORTC web-based library system 
and combined selected items from the PATSAT-C33 and OUT-PATSAT7 questionnaires.  The 
selected scales and individual items included in the IL109 questionnaire are shown in Table 11.3.2 
 
 
 
Table 11.3.2 Scoring the IL109 customized questionnaire (Appendix B) 
Scoring the PATSAT IL109 
Number of items (n) 
Item range* 
item numbers 
(I1, I2, …, In ) 
Scales 
  
D/Technical Skills from PATSAT-C33  
3 
4 
1 – 3 
D/Information Exchange from PATSAT-C33 
3 
4 
4 – 6 
D/Affective Behaviour from PATSAT-C33 
4 
4 
7 – 10 
N Information  from PATSAT-C33 
3 
4 
11 – 13 
N Affective Behaviour from PATSAT-C33 
4 
4 
14 – 17 
Coordination from PATSAT-C33 
4 
4 
18 – 21 
Single items 
Interaction with HCP from PATSAT-C33 altered** 
3 
4 
22,23,24 
Family involvement from PATSAT-C33 
1 
4 
25 
Access/parking from PATSAT-C33 
1 
4 
26 
Access/way from PATSAT-C33 
1 
4 
27 
Continuity from Out-PATSAT7 
1 
4 
28 
Convenience from Out-PATSAT7 altered** 
2 
4 
29,30 
Transition from Out-PATSAT7 altered** 
3 
4 
31,32,33 
Overall care from PATSAT-C33 
1 
4 
34 
D = Doctors; N = Nurses; HCP = health care professional 
* “Item range” is the difference between the possible maximum and the minimum response to 
individual items. All items are scored 1 to 5, giving range = 4. 
**  Altered means selected a subset of items from an multi-item scale and are included as single items in the IL-109 
questionnaire.  
 
Scores derived from the IL109 
 
Raw scores and standardized scores will be derived for each patient for each single-item 
measure and multi-item scale based on the following: 
 
• Raw score 
For each multi-item scale (captured in Table 11.3.2), the responses of the corresponding 
items will be averaged using the following formula: 

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𝑅𝑎𝑤 𝑆𝑐𝑜𝑟𝑒= 𝑅𝑆=
∑𝐼
𝑛1
𝑛, where n represents the number of items in the multi-item scale. 
For each single-item measure, the score of the concerning item corresponds to the raw score.  
 
• Linear transformation 
Raw scores will be standardized to a 0 – 100 range to obtain the score S using the following 
transformation:   
𝑆= (𝑅𝑆−1)
𝑟𝑎𝑛𝑔𝑒∗100 
 
 
The following guidance will be observed to derive the above endpoints for subjects with 
missing response data: 
 
Single-item measures will not be imputed; raw scores and standardized scores for 
unanswered single-item measures will be considered as missing values.   
 
Within a multi-item scale, if at least half of the items have been answered, it will be 
assumed that the missing items have values equal to the average of those items 
which are present for that respondent. This is algebraically equivalent to using all 
the items completed and applying the formulas above to calculate the raw scores 
and standardized scores (i.e., the missing items are ignored when making the 
calculations).   If at least half of the items from the scale have not been answered, 
the raw scores and standardized scores will be considered as missing values.   
 
• Average overall standardized score 
It is acknowledged that the following is not endorsed by the EORTC Data Center: 
 
The average overall standardized score across the six multi-item measures and 13 single-
item measures will be calculated for each subject as the sum of the nonmissing standardized 
scores divided by the number of measures contributing to the sum.  
11.3.3 Definition of Exploratory Endpoint 
Time to initiation of systemic therapy will be calculated as the difference (in days) between the dates of 
enrollment and initiation of systemic therapy (this difference is 0 when treatment initiation occurs on 
the date of enrollment).  A binary variable indicating if the time to initiation of systemic therapy is less 
than 0 (i.e., systemic therapy was initiated prior to date of enrollment) will be determined for each 
subject.  
11.4 
Analysis Populations 
The intent to treat (ITT) population will consist of all randomized subjects.  This population will be 
used to summarize the CONSORT diagram, subject disposition, and baseline subject and disease 

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characteristics.  The evaluable population will consist of all enrolled subjects who meet both of the 
following criteria: 
• Receive at least one dose of standard of care systemic anti-cancer therapy on or after the 
enrollment date 
• Die within six months of enrollment or otherwise are on study for at least 6 months.   
 
The evaluable population will be used for the analyses of all primary, secondary, and exploratory 
endpoints and interim analyses. Select analyses of time to initiation of systemic therapy will be 
conducted on the subset of the evaluable population initiating systemic therapy on study only 
(Section 11.5.6).  Additionally, an intervention-compliant population will be defined as all subjects 
in the evaluable population who meet all of the following criteria: 
 
• Subjects received intervention they were randomized to: 
o Subjects randomized to the ONN arm who have at least one LPNP encounter within 2 
weeks from randomization. 
o Subjects randomized to the control arm who do not have any LPNP encounters within 6 
months from randomization.  
11.5 
Analysis Methods 
11.5.1 Timing of Analysis 
An interim analysis will occur after 100 subjects have been enrolled in the evaluable population. A 
second interim analysis will occur after 85 deaths have occurred in the evaluable population.  A third 
interim analysis will occur after 120 deaths have occurred in the evaluable population. Analyses of the 
primary objectives will occur after 300 subjects have been enrolled in the evaluable population.  A final 
analysis will occur when the OS censoring rate reduces to 20% or when all surviving subjects (who 
remain on study) are on study for at least 30 months (whichever occurs first).     
11.5.2 Subject Disposition 
A summary of all consented subjects will be provided.  This will include a summary of subjects who 
consented, were enrolled, treated, completed study participation, discontinued study participation 
(including reasons), died, were lost to follow-up or withdrew consent.  These summaries will be 
presented in the form of a CONSORT diagram. 
11.5.3 Baseline Subject Characteristics 
A summary of subject demographic, socioeconomic, and disease-related factors will be completed and 
selected subject medical history will be assessed. 
11.5.4 Primary Analysis 
The frequency and proportion of subjects alive at 6 months or better will be calculated for each study 
arm.  Corresponding 95% confidence intervals will be estimated using the Clopper-Pearson method.  A 

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two-sided test for binomial proportions will be carried out, testing the null hypothesis that there is no 
difference in the OS6 rate between the arms.     
 
Poisson regression analyses will be used to analyze acute care utilization visits.  Treatment arm will be 
included in the model as the primary covariate and an asymptotic test of significance will be carried out 
to compare acute care utilization between the arms. 
11.5.5 Secondary Analysis 
Overall survival will be analyzed using Kaplan-Meier techniques.  Tests of statistical significance 
between the arms will be carried out using the log-rank test.  The 12-month survival rate will be 
estimated for each study arm based on the Kaplan-Meier estimates.  A statistical test of significance 
will be carried out to compare the 12-month survival rates between the arms.  This will be 
accomplished by pooling the standard errors of the 12-month OS rates and performing a Chi-Square 
test.  Additional survival analyses and analysis of time from hospice referral to death will be conducted 
using Cox-proportional hazards models.  Thirty-day readmissions will be analyzed using Poisson 
regression.  Length of stay and adherence to clinical care will be analyzed using analysis of variance 
techniques. The frequencies and proportions of subjects referred to Supportive Oncology services will 
be calculated, alongside corresponding 95% confidence intervals estimated using the Clopper-Pearson 
method.  
 
The following models will be estimated for each of the six multi-scale measures, thirteen single-item 
measures, and one average overall standardized score: Linear mixed models for repeated-measures will 
be used to analyze subject-level satisfaction as assessed through the derived endpoints of the EORTC 
IL109 customized questionnaire.  Fixed factors included in the models will be treatment arm, sampling 
time (T1 and T2) and the treatment by time interaction.  A random factor for subject will be included in 
the models to account for repeated observations on the same subject. For single-item measures, mixed-
effects models for repeated ordinal outcomes will be estimated for the thirteen single-item measures 
using ordinal logistic regression. The response outcome may be treated as a 5-level raw score or a 
collapsed version (e.g., 2-level factor as raw scores 1-3 versus 4-5) as appropriate. Similarly, fixed 
factors included in the models will be treatment arm, sampling time (T1 and T2) and the treatment by 
time interaction, and a random factor for subject will be included in the models to account for repeated 
observations on the same subject. 
 
Using the models described above, univariate and multivariable modeling will be conducted to identify 
baseline prognostic factors and to estimate adjusted between-arm treatment effects.  All models will be 
stratified including the stratification factors used in the randomization.  Univariate models will be used 
to identify baseline factors (including subject demographic, socioeconomic, and clinical characteristics) 
that are individually prognostic.  Statistically significance factors identified from the univariate models 
will then be jointly included in a multivariable model.  Backwards elimination will be used to identify 
baseline factors that are independently prognostic.  If it is determined that the sample sizes in some 
stratification strata are too sparse, then strata will be combined prior to analyses.  This will result in a 
smaller number of strata, each with larger sample sizes.     

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11.5.6 Exploratory Analysis 
Descriptive statistics (including, but not limited to, mean and standard deviation, median and range, 
interquartile range) will be calculated to describe the distribution of time to initiation of systemic 
therapy. The frequency and proportion of subjects initiating treatment on study will be calculated for 
each study arm; corresponding 95% confidence intervals will be estimated using the Clopper-Pearson 
method and these proportions will be compared between the arms using Fisher’s Exact tests.   
 
The following will be performed in the subset of evaluable subjects initiating treatment on study only: 
 
Time to initiation of systemic therapy will be compared between the arms using analysis of variance 
techniques. If the distribution is highly skewed, a log transformation may be performed.  
 
Time to initiation of systemic therapy may be summarized as a categorical variable (e.g., time to 
treatment initiation is between 0 and 6 days versus 7+ days) based on the observed distribution in this 
subset of evaluable patients. Outcomes may be evaluated and compared within the ONN arm with 
regards to time to initiation of systemic therapy. Time from enrollment to initiation of systemic therapy 
may assessed separately as both a continuous and categorical measure where appropriate. These 
analyses will be conducted on the primary and secondary endpoints as described above; time from 
enrollment to initiation of systemic therapy may be the comparison/covariate of interest. 
11.5.7 Subset Analysis 
Subset analyses within the ONN arm comparing outcomes for subjects receiving navigation services 
from GI specialist versus general navigation services will be performed.  These analyses will be 
conducted on the primary and secondary endpoints as described above.  
11.5.8 Interim Analysis 
After 100 subjects have been enrolled in the OS evaluable population, a formal interim analysis will be 
conducted.  The interim analysis is designed primarily to assess futility regarding the 6-month OS rate 
objective and will be based on the conditional power.  If the conditional power falls below 50%, the 
OS6 objective may be removed from the co-primary objective.  If this occurs, the primary objective 
will be based only on the acute care utilization objective.  With this revised design, 158 evaluable 
subjects would provide 90% power to detect a 20% reduction in acute care utilization from 6 visits per 
year in the non-navigation arm based on a 2-sided alpha = 0.05 significance level. 
 
If the OS6 conditional power is greater than 50% but less than 80%, the sample size may be increased 
so that the power for the revised sample size is maintained at 80%.  As discussed in Chen et al, 2004, 
this sample size re-estimation will not inflate the type I error. 
 
Sample size re-estimation 
 
As per protocol, the interim futility analysis occurred on 9/22/2022. Based on the results of the interim 
analysis and on the initial statistical design, the trial will proceed with OS6 and ACU as co-primary 

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endpoints. In order to retain 80% power for the OS6 objective, the sample size will be increased from 
107 evaluable subjects per arm to 150 evaluable subjects per arm.   
 
In order to achieve a total of 300 evaluable subjects, it is estimated that approximately a total of 347 
subjects may be enrolled.  
 
Additionally, an interim efficacy analysis analyses will be performed after 85 and 120 deaths in the 
evaluable population have occurred (Interim Efficacy Analysis I and II).  This will be conducted under 
the auspices of the LCI DSMC and will be blinded to the Sponsor-Investigator and the study conduct 
trial site.  If, in the clinical judgement of the LCI DSMC, there are impelling favorable OS trends, the 
study may be terminated due to ethical considerations.  No formal statistical stopping rules will be 
utilized, and no alpha spend will be incurred due to this interim efficacy evaluation.   
 
As per protocol, Interim Efficacy Analysis I occurred on 1/23/2022. Based on the results of the blinded 
survival analysis and the updated statistical design (following the interim futility analysis on 
9/22/2022), the trial will continue and Interim Efficacy Analysis II will be performed after 120 deaths 
in the evaluable population have occurred. 
12. STUDY COMPLETION OR TERMINATION 
12.1 
Completion 
The study will be considered complete when one or more of the following conditions is met: 
• All subjects have withdrawn from the study 
• All subjects have discontinued from the study 
• The IRB, LCI DSMC, or Sponsor-Investigator discontinues the study because of safety 
considerations 
• The Sponsor-Investigator defines an administrative or clinical cut-off date 
12.2 
Termination 
The study will be terminated when one or more of the following conditions occur: 
• If risk-benefit ratio becomes unacceptable owing to, for example, 
o Safety findings from this study 
o Results of parallel clinical studies 
o If the study conduct (e.g., recruitment rate, drop-out rate, data quality, protocol 
compliance) does not suggest a proper completion of the trial within a reasonable time 
frame 
• The Sponsor-Investigator has decided to close the trial at any site and at any time 
 
For any of the above closures, the following applies: 
• Closures should occur only after consultation between involved parties. 
• All affected institutions must be informed as applicable according to local law.   

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• In case of a partial study closure, ongoing subjects, including those in follow- up, must be taken 
care of in an ethical manner. 
13. STUDY MANAGEMENT 
13.1 
IRB Approval  
The study protocol, the informed consent(s) and any other necessary documents must be approved by 
the Sponsor IRB and site(s) IRB of record in accordance with federal regulations and obtained prior to 
implementation.  
 
The Sponsor IRB and sites(s) IRB of record will be informed of any amendment to the protocol, 
informed consent(s), and any other necessary documents in accordance with IRB reporting 
requirements. The study protocol will undergo continuing IRB review based on the level of risk as 
assessed by the IRB no less than annually, or as applicable, in accordance with IRB requirements.  
13.2 
Informed Consent 
Before recruitment and screening/enrollment onto this study, the subject will be given a full 
explanation of the study, the opportunity to review each consent form, and the opportunity to have all 
their questions answered. Prior to a subject’s participation in the trial, the written informed consent(s) 
will be reviewed, signed and personally dated by the subject and by the person who conducted the 
informed consent discussion. Written informed consent may include electronic signatures when use of 
electronic informed consent is obtained from the subject on site or remotely. A copy of each informed 
consent will be given to the subject and each original will be placed in the subject's research record. An 
entry must also be made in the subject's dated source documents to confirm that informed consent was 
obtained prior to any study-related procedures and that the subject received a signed copy.   
13.3 
Protocol Adherence 
Except for an emergency situation in which proper care for the protection, safety, and well-being of the 
study subject requires alternative treatment, the study shall be conducted exactly as described in the 
approved protocol.   
13.3.1 Amendments to the Protocol and Informed Consent 
If it is necessary for the study protocol to be amended and/or the informed consent revised, the 
amendment or a new version of the study protocol and/or revised informed consent must be approved 
by the Sponsor-Investigator and the Sponsor IRB. 
13.4 
Other Protocol Deviations  
If a deviation occurs, the event should be reported promptly to the Sponsor-Investigator promptly. Any 
IRB reportable event that occurs must be reported to the IRB per IRB reporting requirements and to the 
Sponsor-Investigator as soon as possible but no later than 10 business days of awareness. 

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Protocol deviations that, in the Investigator’s judgment, potentially caused harm to participants or 
others or indicates that the participants or others are at an increased risk of harm, or has adversely 
impacted data integrity will be reported promptly to the IRB per IRB reporting requirements.  
Planned protocol deviations should be submitted to the Sponsor for approval prior to the anticipated 
deviation occurring. After Sponsor approval has been obtained, planned deviations should be submitted 
to the IRB prior to the anticipated deviation occurring. IRB approval must be obtained prior to 
deviation occurrence. No exceptions for eligibility criteria are not allowed. 
13.5 
Retention of Records 
Essential documentation (e.g., source documents, Sponsor-Investigator correspondence, monitoring 
reports, and regulatory documents), including all IRB correspondence, will be retained for at least 2 
years after the investigation is completed.  Documentation will be readily available upon request. 
13.6 
Ethical and Legal Conduct of the Study 
The procedures set out in this protocol, pertaining to the conduct, evaluation, and documentation of this 
study, are designed to ensure that the Investigator abide by GCP guidelines.  The study will also be 
carried out in full conformity with Regulations for the Protection of Human Subjects of Research 
codified in the ICH E6 and in keeping with applicable local law(s) and regulation(s). 
 
Documented approval from appropriate agencies will be obtained for all participating centers before the 
start of the study, according to GCP, local laws, regulations and organizations.  
 
Strict adherence to this protocol is required for all aspects of study conduct; the investigators may not 
modify or alter the procedures described in this protocol.   
 
The Sponsor-Investigator is responsible for the conduct of the trial at the sites in accordance with the 
Declaration of Helsinki.  The Sponsor-Investigator is responsible for overseeing all study subjects.  The 
Sponsor-Investigator must assure that all study site personnel, including sub-investigators and other 
study staff members, adhere to the study protocol and all applicable regulations and guidelines 
regarding clinical trials both during and after study completion. 
 
The Sponsor-Investigator will be responsible for assuring that all the required data will be collected and 
properly documented. 
13.7 
Confidentiality of Records 
All records identifying the subject will be kept confidential and, to the extent permitted by the 
applicable laws and/or regulations, will not be made publicly available. 
 

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13.8 
Compliance with ClinicalTrials.gov 
The Sponsor-Investigator is solely responsible for determining whether the trial and its results are 
subject to the requirements for submission to ClinicalTrials.gov (http://www.clinicaltrials.gov).  
 
 

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REFERENCES 
1. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA: A Cancer Journal for Clinicians. 
2019;69(1):7-34. 
2. 
Prades J, Remue E, van Hoof E, Borras JM. Is it worth reorganising cancer services on the basis 
of multidisciplinary teams (MDTs)? A systematic review of the objectives and organisation of MDTs 
and their impact on patient outcomes. Health Policy. 2015;119(4):464-74. 
3. 
Kesson EM, Allardice GM, George WD, Burns HJ, Morrison DS. Effects of multidisciplinary 
team working on breast cancer survival: retrospective, comparative, interventional cohort study of 13 
722 women. BMJ. 2012;344:e2718. 
4. 
Kelly SL, Jackson JE, Hickey BE, Szallasi FG, Bond CA. Multidisciplinary clinic care 
improves adherence to best practice in head and neck cancer. Am J Otolaryngol. 2013;34(1):57-60. 
5. 
Friedman EL, Kruklitis RJ, Patson BJ, Sopka DM, Weiss MJ. Effectiveness of a thoracic 
multidisciplinary clinic in the treatment of stage III non-small-cell lung cancer. J Multidiscip Healthc. 
2016;9:267-74. 
6. 
Bunnell CA, Weingart SN, Swanson S, Mamon HJ, Shulman LN. Models of multidisciplinary 
cancer care: physician and patient perceptions in a comprehensive cancer center. J Oncol Pract. 
2010;6(6):283-8. 
7. 
van Ryn M, Phelan SM, Arora NK, Haggstrom DA, Jackson GL, Zafar SY, et al. Patient-
reported quality of supportive care among patients with colorectal cancer in the Veterans Affairs Health 
Care System. J Clin Oncol. 2014;32(8):809-15. 
8. 
Walsh KE, Dodd KS, Seetharaman K, Roblin DW, Herrinton LJ, Von Worley A, et al. 
Medication errors among adults and children with cancer in the outpatient setting. J Clin Oncol. 
2009;27(6):891-6. 
9. 
Martin J, Halm EA, Tiro JA, Merchant Z, Balasubramanian BA, McCallister K, et al. Reasons 
for Lack of Diagnostic Colonoscopy After Positive Result on Fecal Immunochemical Test in a Safety-
Net Health System. Am J Med. 2017;130(1):93 e1- e7. 
10. 
Fogel EL, Shahda S, Sandrasegaran K, DeWitt J, Easler JJ, Agarwal DM, et al. A 
Multidisciplinary Approach to Pancreas Cancer in 2016: A Review. Am J Gastroenterol. 
2017;112(4):537-54. 
11. 
Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: 
descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 
2014;23(5):700-13. 
12. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. 
13. 
Bilimoria KY, Bentrem DJ, Ko CY, Stewart AK, Winchester DP, Talamonti MS. National 
failure to operate on early stage pancreatic cancer. Ann Surg. 2007;246(2):173-80. 
14. 
Aizer AA, Chen MH, McCarthy EP, Mendu ML, Koo S, Wilhite TJ, et al. Marital status and 
survival in patients with cancer. J Clin Oncol. 2013;31(31):3869-76. 
15. 
Walker GV, Grant SR, Guadagnolo BA, Hoffman KE, Smith BD, Koshy M, et al. Disparities in 
stage at diagnosis, treatment, and survival in nonelderly adult patients with cancer according to 
insurance status. J Clin Oncol. 2014;32(28):3118-25. 

Protocol: LCI-GI-NOS-NAV-001 
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16. 
Chavez-MacGregor M, Clarke CA, Lichtensztajn DY, Giordano SH. Delayed Initiation of 
Adjuvant Chemotherapy Among Patients With Breast Cancer. JAMA Oncol. 2016;2(3):322-9. 
17. 
Graboyes EM, Kompelli AR, Neskey DM, Brennan E, Nguyen S, Sterba KR, et al. Association 
of Treatment Delays With Survival for Patients With Head and Neck Cancer: A Systematic Review. 
JAMA Otolaryngol Head Neck Surg. 2018. 
18. 
Weiner AB, Keeter MK, Manjunath A, Meeks JJ. Discrepancies in staging, treatment, and 
delays to treatment may explain disparities in bladder cancer outcomes: An update from the National 
Cancer Data Base (2004-2013). Urol Oncol. 2018;36(5):237 e9- e17. 
19. 
Bilimoria KY, Ko CY, Tomlinson JS, Stewart AK, Talamonti MS, Hynes DL, et al. Wait times 
for cancer surgery in the United States: trends and predictors of delays. Ann Surg. 2011;253(4):779-85. 
20. 
Shapiro M, Chen Q, Huang Q, Boosalis VA, Yoon CH, Saund MS, et al. Associations of 
Socioeconomic Variables With Resection, Stage, and Survival in Patients With Early-Stage Pancreatic 
Cancer. JAMA Surg. 2016;151(4):338-45. 
21. 
Zhang G, Zhao X, Li J, Yuan Y, Wen M, Hao X, et al. Racial disparities in stage-specific 
gastric cancer: analysis of results from the Surveillance Epidemiology and End Results (SEER) 
program database. J Investig Med. 2017;65(6):991-8. 
22. 
Wong TH, Lau ZY, Ong WS, Tan KB, Wong YJ, Farid M, et al. Cancer patients as frequent 
attenders in emergency departments: A national cohort study. Cancer Med. 2018;7(9):4434-46. 
23. 
Delgado Guay MO, Tanzi S, San Miguel Arregui MT, Chisholm G, De la Cruz MG, Bruera E. 
Characteristics and outcomes of advanced cancer patients who miss outpatient supportive care consult 
appointments. Support Care Cancer. 2014;22(10):2869-74. 
24. 
Kheirkhah P, Feng Q, Travis LM, Tavakoli-Tabasi S, Sharafkhaneh A. Prevalence, predictors 
and economic consequences of no-shows. BMC Health Serv Res. 2016;16:13. 
25. 
Chaiyachati KH, Hubbard RA, Yeager A, Mugo B, Lopez S, Asch E, et al. Association of 
Rideshare-Based Transportation Services and Missed Primary Care Appointments: A Clinical Trial. 
JAMA Intern Med. 2018;178(3):383-9. 
26. 
Handley NR, Schuchter LM, Bekelman JE. Best Practices for Reducing Unplanned Acute Care 
for Patients With Cancer. J Oncol Pract. 2018;14(5):306-13. 
27. 
Freeman HP. Patient navigation: a community centered approach to reducing cancer mortality. J 
Cancer Educ. 2006;21(1 Suppl):S11-4. 
28. 
American College of Surgeons - Commission on Cancer. Cancer Program Standards 2012: 
Ensuring Patient-Centered Care. Chicago, IL2012. 
29. 
Freeman HP, Muth BJ, Kerner JF. Expanding access to cancer screening and clinical follow-up 
among the medically underserved. Cancer Pract. 1995;3(1):19-30. 
30. 
DeGroff A, Schroy PC, 3rd, Morrissey KG, Slotman B, Rohan EA, Bethel J, et al. Patient 
Navigation for Colonoscopy Completion: Results of an RCT. Am J Prev Med. 2017;53(3):363-72. 
31. 
Braun KL, Thomas WL, Jr., Domingo JL, Allison AL, Ponce A, Haunani Kamakana P, et al. 
Reducing cancer screening disparities in medicare beneficiaries through cancer patient navigation. J 
Am Geriatr Soc. 2015;63(2):365-70. 
32. 
Ramirez A, Perez-Stable E, Penedo F, Talavera G, Carrillo JE, Fernandez M, et al. Reducing 
time-to-treatment in underserved Latinas with breast cancer: the Six Cities Study. Cancer. 
2014;120(5):752-60. 

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33. 
Lobb R, Allen JD, Emmons KM, Ayanian JZ. Timely care after an abnormal mammogram 
among low-income women in a public breast cancer screening program. Arch Intern Med. 
2010;170(6):521-8. 
34. 
Castaldi M, Safadjou S, Elrafei T, McNelis J. A Multidisciplinary Patient Navigation Program 
Improves Compliance With Adjuvant Breast Cancer Therapy in a Public Hospital. Am J Med Qual. 
2017;32(4):406-13. 
35. 
Whitley EM, Raich PC, Dudley DJ, Freund KM, Paskett ED, Patierno SR, et al. Relation of 
comorbidities and patient navigation with the time to diagnostic resolution after abnormal cancer 
screening. Cancer. 2017;123(2):312-8. 
36. 
Gordils-Perez J, Schneider SM, Gabel M, Trotter KJ. Oncology Nurse Navigation: 
Development and Implementation of a Program at a Comprehensive Cancer Center. Clin J Oncol Nurs. 
2017;21(5):581-8. 
37. 
Fiscella K, Whitley E, Hendren S, Raich P, Humiston S, Winters P, et al. Patient navigation for 
breast and colorectal cancer treatment: a randomized trial. Cancer Epidemiol Biomarkers Prev. 
2012;21(10):1673-81. 
38. 
Freund KM, Battaglia TA, Calhoun E, Darnell JS, Dudley DJ, Fiscella K, et al. Impact of 
patient navigation on timely cancer care: the Patient Navigation Research Program. J Natl Cancer Inst. 
2014;106(6):dju115. 
39. 
Rocque GB, Pisu M, Jackson BE, Kvale EA, Demark-Wahnefried W, Martin MY, et al. 
Resource Use and Medicare Costs During Lay Navigation for Geriatric Patients With Cancer. JAMA 
Oncol. 2017;3(6):817-25. 
40. 
Jahn P, Kuss O, Schmidt H, Bauer A, Kitzmantel M, Jordan K, et al. Improvement of pain-
related self-management for cancer patients through a modular transitional nursing intervention: a 
cluster-randomized multicenter trial. Pain. 2014;155(4):746-54. 
41. 
Fischer SM, Kline DM, Min SJ, Okuyama-Sasaki S, Fink RM. Effect of Apoyo con Carino 
(Support With Caring) Trial of a Patient Navigator Intervention to Improve Palliative Care Outcomes 
for Latino Adults With Advanced Cancer: A Randomized Clinical Trial. JAMA Oncol. 
2018;4(12):1736-41. 
42. 
Kowalkowski M, Raghavan D, Blackley K, Morris V, Farhangfar CJ. 12 month survival for 
oncology patients with versus without patient navigation. 2016;34(15_suppl):6510-. 
43. 
Kowalkowski M, Blackley K, Farhangfar CJ. Acute care reliance among patients with advanced 
cancer with or without nurse navigation. 2017;35(15_suppl):e18303-e. 
 
 
 

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APPENDIX A 
Patient Navigation Acuity Grading Scale 
 
I. 
PURPOSE: To assess patient acuity level as they are navigated through 
the cancer continuum. To assist the navigator in developing an appropriate 
plan of care and the ability to prioritize patients with the greatest barriers 
to care. To document and track the level of care and effort required based 
on the level of patient need. 
 
II. 
POLICY: The navigator will perform an assessment of the patient acuity 
level and document in the patient record. This assessment will be made using 
the "Acuity Grading Scale" and will be performed at the time the intake form 
is completed. The acuity level of a patient may increase or decrease at any 
time during care due to a change in patient circumstances. If a change occurs, 
it should be documented accordingly in the patient record. 
 
Ill. 
PROCEDURE: 
A. The navigator will assess the patient's level of acuity using the 
Acuity Grading Scale at the time the intake form is completed. 
B. The acuity level will be recorded in the patient's medical record. 
C. The navigator will develop a plan of care based on the patient acuity level. 
D. If the patient acuity changes at any time, the navigator will update 
the acuity level in the patient record. 
E. If the patient has any urgent issues at the time of the assessment, the 
navigator will contact the appropriate staff immediately. 
 
 
 
 
 

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Patient Navigation Acuity Scale 
 
Level I-Initial patient contact when referral received 
--Initial guidance/education/coordination as needed 
--Typically no follow up required 
 
Level 2-Initial patient contact when referral received 
--Initial guidance/education/coordination 
--Basic needs identified* 
--Ongoing guidance/education throughout treatment as 
needed 
 
Level 3-Initial patient contact when referral received 
--Coordination of multimodality treatment 
--Moderate intensity needs identified* 
--Ongoing guidance/education provided throughout treatment 
 
Level 4-Initial patient contact when referral received 
--Coordination of multimodality treatment 
--High intensity needs* 
--Difficulty coping with diagnosis or treatment 
--Ongoing guidance/education/support provided throughout 
the patient's treatment 
 
*Please refer to the provided reference guide (next page) 
 
Reference Guide for Acuity Scale 
Basic  needs:  (including,  but not limited to) 
--Survivorship programs 
--Educational needs 

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--Assistance expediting appointments 
--Genetics referral 
 
Moderate intensity needs: (including, but not limited to) 
--Supply needs 
--Nutritional support 
--Transportation issues 
--Fertility Services 
--Emotional needs 
--Absence of support 
 
High intensity needs: (including, but not limited to) 
--Language barrier 
--Uninsured or under insured 
--Illegal status 
--Low health literacy 
--Psychological issues 
--Unresolved symptoms 
--Frequent hospitalization 
--Coordination with outside facilities 
--Child/elder care 

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• 
Carolinas HealthCare System 
Levine Cancer Institute 
 
Patient Navigation Acuity Grading Scale 
Page 1 of 1 
 
Reviewed: 6/17 
 
I. 
PURPOSE: To assess patient acuity level as they are navigated through 
the cancer continuum. To assist the navigator in developing an appropriate 
plan of care and the ability to prioritize patients with the greatest barriers to 
care. To document and track the level of care and effort required based on 
the level of patient need. 
 
II. 
POLICY: The navigator will perform an assessment of the patient acuity 
level and document in the patient record. This assessment will be made using 
the "Acuity Grading Scale" and will be performed at the time the intake form is 
completed. The acuity level of a patient may increase or decrease at any 
time during care due to a change in patient circumstances. If a change 
occurs, it should be documented accordingly in the patient record. 
 
Ill. 
PROCEDURE: 
A. The navigator will assess the patient's level of acuity using the Acuity 
Grading Scale at the time the intake form is completed. 
B. The acuity level will be recorded in the patient's medical record. 
C. The navigator will develop a plan of care based on the patient acuity level. 
D. If the patient acuity changes at any time, the navigator will update the 
acuity level in the patient record. 
E. If the patient has any urgent issues at the time of the assessment, the 
navigator will contact the appropriate staff immediately. 
 
 
 
 
 
 
 
 
Jeffrey Kneisl, MD and Co-Chairman of the Cancer Committee 
 

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APPENDIX B  
 
 

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