Clinical trial NCT03870529
Conditions: Non Small Cell Lung Cancer Stage I Lung Cancer Stage Ib Lung Carcinoma Stage IA Lung Carcinoma AJCC V7 Stage IIA Lung Carcinoma Stage IIIA Lung Carcinoma
Sponsor: Wake Forest University Health Sciences
Start date: 2019-08-19; Completion date: 2022-12-09
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This trial studies how well high dose vitamin A compound works in treating participants with non-small cell lung cancer that can be removed by surgery. Vitamin A compound may increase the number of germinal centers (immune centers that make antibodies mature) in tumor and lymph tissues which may be beneficial to patients with cancer.

Detailed description:
PRIMARY OBJECTIVES:

I. To compare the percentage of resected cancers containing germinal centers (GCs) in patients who receive neoadjuvant vitamin A compound (vitamin A) to controls.

SECONDARY OBJECTIVES:

I. To compare the abundance of GCs in adjacent lymph nodes in patients who receive neoadjuvant vitamin A to controls.

II. To compare histopathologic responses based on tumor necrosis in lung cancer patients who receive neoadjuvant vitamin A to controls.

III. To compare overall survival of patients who receive neoadjuvant vitamin A to controls.

EXPLORATORY OBJECTIVES:

I. To describe immunophenotypic changes of monocytes including myeloid derived suppressor cells (MDSCs) in pre- and post-treatment blood samples.

OUTLINE: Participants are randomized to 1 of 2 groups.

GROUP I: Participants receive vitamin A compound orally (PO) for 7 consecutive days in the absence of disease progression or unacceptable toxicity. Within 21 days of completing treatment, participants then undergo surgical resection.

GROUP II: Participants undergo surgical resection.

After completion of study treatment, participants are followed up for 30 days.

Arms: arm 1: Participants receive vitamin A compound PO for 7 consecutive days in the absence of disease progression or unacceptable toxicity. Within 21 days of completing treatment, participants then undergo surgical resection. arm 2: Description Participants undergo surgical resection.
Interventions: intervention 1: Vitamin A Compound intervention 2: Therapeutic Conventional Surgery
Intervention descriptions: intervention 1: Participants randomized to this arm will receive 7 consecutive days of of Vitamin A compound without disease progression or unacceptable toxicities. Within 21 days of completion of treatment participants will undergo surgical resection intervention 2: Participants randomized to this arm will receive surgical resection

Protocol documents:
Prot_SAP_001.pdf: 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
ClinicalTrials.gov:  NCT03870529
Co-Principal Investigators: 
W. Jeffrey Petty, MD
Section on Hematology and Oncology
Wake Forest Baptist Medical Center
Medical Center Boulevard
Winston-Salem, NC 27157
Jim Wudel, MD  
Department of Surgical Sciences, Section on 
Cardiothoracic Surgery 
Wake Forest Baptist Medical Center 
Medical Center Boulevard 
Winston-Salem, NC 27157 
Karen M. Haas, PhD 
Department of Microbiology and Immunology 
Wake Forest Baptist Medical Center 
575 N. Patterson Ave. 
2E-024 Biotech Place 
Winston-Salem, NC 27157 
Frank Marini, PhD 
Director, Center for Regenerative Imaging and Cell 
Imaging Shared Resource 
Wake Forest Institute of Regenerative Medicine 
Winston-Salem, NC 27101 
Alexei Mikhailov, MD 
Department of Pathology 
Wake Forest Baptist Medical Center 
Winston-Salem, NC 27101 
Pierre Triozzi, MD 
Section on Hematology and Oncology 
Wake Forest Baptist Medical Center 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
 
 
Co-Investigator(s):  
 
Thomas Lycan, DO 
Hematology & Oncology  
Wake Forest Baptist Medical Center 
Medical Center Boulevard 
Winston-Salem, NC 27157 
  
 
 
Payal Gandhi, PA-C 
Section on Hematology and Oncology 
Wake Forest Baptist Medical Center 
 
 
 
Jennifer Z. Miller, PharmD 
Oncology Clinical Specialist 
Pharmacy Department 
Wake Forest Baptist Medical Center 
Greg Hawkins, PhD 
Center for Human Genomics 
Wake Forest Baptist Medical Center 
 
Biostatistician: 
 
 
Beverly Levine, PhD 
Biostatistics Core 
Comprehensive Cancer Center 
Wake Forest Baptist Medical Center 
Medical Center Boulevard  
Winston-Salem, NC 27157 
 
 
Tissue Procurement Officer: 
Elizabeth McWilliams 
Wake Forest Baptist Medical Center 
 
 
 
 
 
 
Research Nurse: 
 
 
Sharon Averill 
Comprehensive Cancer Center of Wake Forest  
Baptist Medical Center 
 
 
 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
 
 
Study Coordinator:  
 
Jeffrey Kettler 
Comprehensive Cancer Center of Wake Forest  
Baptist Medical Center 
 
 
 
 
 
 
 
 
 
 
 
 
Data Management:  
 
Amy Hughes 
Comprehensive Cancer Center of Wake Forest  
Baptist Medical Center 
 
Regulatory Contact:  
 
Cindy Miller 
Comprehensive Cancer Center of Wake Forest  
Baptist Medical Center 
 
 
 
Participating Institution(s):  
WFBCCC 
 
 
Version Date: 
 
 
07/26/18 
 
Amended: 
 
 
 
05/18/21 
 
 
Confidential


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
 
 
                                              Page 4 of 43 
 
Table of Contents 
Schema ......................................................................................................................................... 6 
1.0 
Introduction and Background ............................................................................................ 7 
2.0 
Objectives ......................................................................................................................... 9 
2.1 
Primary Objective .......................................................................................................... 9 
2.2 
Secondary Objective(s) ................................................................................................. 9 
2.3 
Exploratory Objectives .................................................................................................. 9 
3.0 
Patient Selection ............................................................................................................... 9 
3.1 
Inclusion Criteria............................................................................................................ 9 
3.2 
Exclusion Criteria .......................................................................................................... 9 
3.3 
Inclusion of Women and Minorities ............................................................................. 10 
4.0 
Registration Procedures .................................................................................................. 10 
5.0 
Study Outcomes and Study Measures ............................................................................ 11 
5.1 
Primary Outcome ........................................................................................................ 11 
5.2 
Secondary Outcomes .................................................................................................. 11 
6.0 
Treatment Plan ................................................................................................................ 11 
6.1 
Study-Related Interventions ........................................................................................ 12 
6.2 
Treatment Administration ............................................................................................ 12 
6.2.1 
Dose Modifications ................................................................................................ 12 
6.3 
General Concomitant Medication and Supportive Care Guidelines ............................ 13 
6.4 
Duration of Therapy..................................................................................................... 13 
6.5 
Duration of Follow Up .................................................................................................. 13 
7.0 
Measurement of Effect .................................................................................................... 13 
7.1.1 
Methods for Pathologic Evaluation ........................................................................ 13 
7.1.2 
Assessment for efficacy ........................................................................................ 13 
8.0 
Adverse Events List and Reporting Requirements ......................................................... 14 
8.1 
Adverse Event List for Vitamin A ................................................................................. 14 
8.2 
Adverse Event Characteristics .................................................................................... 14 
8.4 
STRC SAE Reporting Requirements .......................................................................... 15 
8.5  
WFUHS IRB AE Reporting Requirements .................................................................. 15 
9.0 
Pharmaceutical Information ............................................................................................ 16 
9.1 
Pharmaceutical Accountability .................................................................................... 16 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
 
 
                                              Page 5 of 43 
9.2 
Vitamin A ..................................................................................................................... 16 
10.0 
Data Management ........................................................................................................... 17 
11.0 
Statistical Considerations ................................................................................................ 17 
11.1 
Power and Sample Size .............................................................................................. 17 
11.2 
Method of Randomization ........................................................................................... 17 
11.3 
Analysis of Primary Objective ...................................................................................... 17 
11.5 
Analysis of Exploratory Objective ................................................................................ 18 
11.6 
Estimated Accrual Rate ............................................................................................... 18 
11.7 
Estimated Study Length .............................................................................................. 18 
References .................................................................................................................................. 19 
Appendix A – Protocol Registration Form ................................................................................... 21 
Appendix B – Subject Eligibility Checklist ................................................................................... 22 
Appendix C – Mandatory DSMC SAE Reporting Guidelines ...................................................... 24 
Appendix D – Baseline Tobacco Use ......................................................................................... 31 
Appendix E – Adverse Events Log ............................................................................................. 34 
Appendix F – Outcomes Data Collection Form ........................................................................... 35 
Appendix G – Survival Form ....................................................................................................... 36 
Appendix H – Exploratory Outcomes Data Collection Form ....................................................... 37 
Appendix I– Medical History ....................................................................................................... 38 
Appendix J – Vitals Form ............................................................................................................ 39 
Appendix K - Withdrawal of consent for the intervention and medical record use ...................... 41 
Appendix L - Vitamin A Medication Log ...................................................................................... 42 
Appendix M – Pre-Toxicity .......................................................................................................... 43 
 
 
 
 
 
 
 
 
 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
 
 
                                              Page 6 of 43 
Schema 
 
 
 
Vitamin A  
10,000 IU daily for 7 days 
Biopsy– Findings 
Diagnostic or Suspicious 
for NSCLC 
Evaluation by 
Thoracic Surgery 
Screening, Consent, 
Registration, 
Randomization 
Surgical Resection with 21 Days 
of Completing Treatment 
Pathologic Evaluation with 
Quantification of GCs 
Surgical Resection 
Pathologic Evaluation with 
Quantification of GCs 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
 
 
                                              Page 7 of 43 
1.0 
Introduction and Background 
 
Immunotherapy is rapidly replacing chemotherapy as the most effective treatment for 
non-small cell lung cancer.  Immunotherapy resistance is complex and different factors 
may be responsible for individual patients with immunotherapy resistant lung cancers.  
Vitamin A deficiency is associated with increased risk of lung cancer, and this deficiency 
also has been associated with poor immune system function.  Our proposed study seeks 
to improve immune system function in the neoadjuvant setting by treating patients with 
vitamin A prior to surgical resection for non-small cell lung cancer.  The main endpoints 
of the study will be to evaluate the development of germinal centers in resected cancers 
and adjacent lymph nodes, histopathologic responses, and changes in immunologic 
biomarkers. 
 
Vitamin A deficiency was first observed to reduce immune system function and increase 
risk of pulmonary infections in the early 1900s.  This deficiency laterwas found to 
increase lung cancer risk in the 1960s.  This observation gave rise to the concept of 
chemoprevention with the use of vitamin A or its derivatives proposed to reduce lung 
cancer risk [1].  Two chemically distinct but related classes of compounds were 
investigated for this purpose: retinoids and carotenoids.  Retinoids are compounds that 
are highly similar to vitamin A (retinol).  Retinoids have a single cyclic end group and a 
hydrophilic side chain.  These compounds function by binding to retinoid receptors and 
altering transcription [2-7].  The molecular weights of retinoid compounds are similar to 
retinol (mw=286.5 g/mol).  Carotenoids are much larger compounds (for beta carotene, 
mw = 536.9 g/mol) that contain multiple cyclic structures.  These compounds do not 
directly interact with retinoic acid receptors.  Certain carotenoids including beta carotene 
are prodrugs of vitamin A and can be converted to vitamin A through enzymatic 
cleavage in the intestine although the majority of beta-carotene enters the blood stream 
unchanged [8].  Carotenoids are felt to produce beneficial effects by serving as 
antioxidants in addition to functioning as pro-vitamins.  Unfortunately, in the presence of 
tobacco carcinogens, beta-carotene undergoes eccentric cleavage leading to the 
formation of DNA damaging organic molecules, decreased retinoic acid concentrations 
in lung tissue [8, 9].  Unexpectedly, these drugs have also been shown to increase the 
development of epithelial pre-neoplasia [9].      
 
 
Large clinical chemoprevention studies of retinoid or carotenoid supplementation have 
been negative with the indication of harm for beta-carotene supplementation in patients 
who continue to smoke [10-12].  The studies that examined beta-carotene and 
demonstrated increased risk of lung cancer for high risk populations included CARET 
and ATBC [11, 12].  Another study specifically examined the effects of the retinoid, 
retinyl palmitate, which will be used in the current study.  In this study, called 
EUROSCAN, 2592 patients were randomized to receive retinyl palmitate or not and no 
change in cancer risk was observed for patients receiving retinyl palmitate in the entire 
population as well as the smoking and non-smoking cohorts [10]. Based on the concerns 
regarding beta-carotene and the lack of harm observed with retinyl palmitate in 
EUROSCAN, current practice guidelines recommend that patients who currently smoke 
should avoid high dose beta-carotene supplements but no such recommendations are 
made for avoiding vitamin A or retinyl palmitate which will be used in the current study 
[13].   
 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
 
 
                                              Page 8 of 43 
The doses of retinyl palmitate used in prior chemoprevention studies have been much 
higher that what is currently recommended as a vitamin supplement.  In the EURSOCAN 
study, patients received 300,000 IU of retinyl palmitate daily for the first year followed by 
150,000 IU daily for the second year.  To reduce risk of acute toxicity, a fifteen fold lower 
dose, 10,000 IU, was selected for this study.  This dose is recommended for the 
prevention of vitamin A deficiency and is the upper limit of the current recommended 
daily intake. 
 
 
While prior studies dampened enthusiasm in the retinoid chemoprevention field, the use 
of retinoids for lung cancer treatment has shown some promise particularly in 
combination with targeted agents.  In a prior neoadjuvant study, the non-classical 
retinoid, bexarotene, demonstrated biological effects on cancer tissues even with a 
short, one week course of treatment [14].  Vitamin A itself and other classical retinoids 
are known to have beneficial effects on immune system function, and the effectiveness 
of vitamin A in combination with PD-1 drugs has not been adequately studied. 
 
Vitamin A and other retinoids function by activating nuclear receptors including retinoic 
acid receptors (RARs) and retinoid X receptors (RXRs) [3, 6, 7].  Activation of these 
nuclear receptors leads to transcription of target genes and changes in cellular function.  
Several lines of evidence support an important role for vitamin A to support immune 
system function.  Vitamin A deficiency increases risk of infections in experimental 
models.  Also, vitamin A supplementation reduces mortality from infectious 
complications in populations with a high risk of deficiency.  Furthermore, vitamin A 
supplementation has been shown to improve antibody titers in response to vaccination in 
clinical trials.   
 
The mechanisms through which vitamin A promotes immune system function are 
complex and involve both B-cell and T-cell mediated effects.  The focus of the current 
study will be to examine changes in B-cell function although T-cell subsets will also be 
examined.  In published studies from preclinical models, retinoid treatment of B-cells has 
been shown to increase cellular proliferation, improve antibody diversification through 
somatic hypermutation, and increase immunoglobulin production.  In addition, animal 
models have shown that retinoid treatment increases formation of germinal centers 
which are critical for B-cell maturation. 
 
Given the opportunities to improve patient outcomes by improving immunologic function, 
investigation of vitamin A supplementation in patients with lung cancer is an exciting 
opportunity to investigate an immunologic active treatment with minimal toxicities.  
Vitamin A treatment side effects can occur following prolonged exposure to very high 
doses but are extremely uncommon with shorter courses of treatment.  Changes in 
cellular function, however, are quite rapid with target gene expression changes occurring 
within 24 hours.  Increases in germinal center (GC) formation triggered by retinoids are 
seen in animal models following 6 days of retinoid treatment with measurements 
performed on day 10 (4 days after completing retinoid treatment) [15]. For this study we 
will examine a 7-day period of treatment with vitamin A in a window-of -opportunity 
neoadjuvant setting.   
 
In our study, we will examine clinical outcomes including pathologic response and 
overall survival.   The rational for induction of GC formation improving outcomes arises 
from an early study of resected lung cancers found that primary lung cancers with GC 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
 
 
                                              Page 9 of 43 
formation have lower risk of nodal metastases [16].  Although underpowered for 
statistical comparison, the risk of relapse and overall survival appeared improved in 
tumors with GCs in this study as well.  These findings suggest that inducing GC 
formation with vitamin A could lead to improved survival for early stage lung cancer 
patients. 
2.0 
Objectives 
2.1 
Primary Objective 
 
2.1.1 To compare the percentage of resected cancers containing germinal 
centers (GCs) in patients who receive neoadjuvant vitamin A to controls.  
2.2 
Secondary Objective(s) 
2.2.1 To compare the abundance of GCs in adjacent lymph nodes in patients 
who receive neoadjuvant vitamin A to controls.  
 
2.2.2 To compare histopathologic responses based on tumor necrosis in lung 
cancer patients who receive neoadjuvant vitamin A to controls. 
 
2.2.3 To compare overall survival of patients who receive neoadjuvant vitamin 
A to controls.   
2.3 
Exploratory Objectives 
 
2.3.1 To describe immunophenotypic changes of monocytes including myeloid 
derived suppressor cells (MDSCs) in pre- and post-treatment blood 
samples. 
3.0 
Patient Selection 
3.1 
Inclusion Criteria  
 
 
 
 
 
 
 
 
   
 
 
 
 
3.1.1  Patient must be > 18 years of age 
 
3.1.2 Patients must have either biopsy proven or radiographically suspected 
non-small cell lung cancer. 
 
 
 
 
 
 
 
3.1.3 Patients must have disease in the chest that is felt to be surgically 
resectable. 
 
3.1.4 ECOG performance status of 0-2. 
 
3.1.5 Ability to understand and the willingness to sign an IRB-approved 
informed consent document 
3.2 
Exclusion Criteria  
 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
 
 
                                              Page 10 of 43 
3.2.1  Patients < 18 years of age 
 
3.2.2 Women who are pregnant or breast feeding. 
 
3.2.3 Patients may not be receiving any other investigational agents for the 
treatment of NSCLC. 
 
3.2.4  Patients may not be taking the following medications: high dose vitamin 
A supplement (multivitamin supplements prohibited only if vitamin A 
content is greater than 3,500 IU), bexarotene, alitretinoin, tretinoin, 
adapalene, isotretinoin, acetretin, doxycycline, minocycline, or 
demeclocycline,   
 
3.2.5 Uncontrolled intercurrent illness including, but not limited to, pancreatitis, 
ongoing or active infection, symptomatic congestive heart failure, 
unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social 
situations that would limit compliance with study requirements. 
 
3.2.6  Hypervitaminosis A – toxic effects of ingesting too much vitamin A 
3.3 
Inclusion of Women and Minorities 
 
Men and women of all races and ethnicities who meet the above-described 
eligibility criteria are eligible to participate in this study.  
 
The study consent form will also be provided in Spanish for Spanish-speaking 
participants. Based on CCCWFU population estimates, we expect approximately 
40% of participants to be women. Translating this to our sample size estimate of 
180, we plan to enroll at least 48 women. Similarly, we expect approximately 5% 
of study participants to be Hispanic/Latino (N=6). We plan to enroll at least 15% 
Black or African American (N=18), no American Indian/Alaska Natives, 5% Asian 
(N=6). Should we not meet or exceed these estimates, the PI will engage the 
Cancer Center Health Equity Advisory Group to discuss strategies to enhance 
recruitment in these target populations. 
4.0 
Registration Procedures 
 
All patients entered on any CCCWFU trial, whether treatment, companion, or cancer control 
trial, must be linked to a study in EPIC within 24 hours of Informed Consent. Patients must be 
registered prior to the initiation of treatment.   
 
You must perform the following steps in order to ensure prompt registration of your patient: 
 
1. Complete the Eligibility Checklist (Appendix B) 
2. Complete the Protocol Registration Form (Appendix A) 
3. Alert the Cancer Center registrar by phone, and then send the signed Informed 
Consent Form, Eligibility Checklist and Protocol Registration Form to the registrar, 
either by fax or e-mail. 
Contact Information: 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
 
 
                                              Page 11 of 43 
Protocol Registrar PHONE (336) 713-6767 
Protocol Registrar FAX (336) 713-6772 
Protocol Registrar E-MAIL (registra@wakehealth.edu) 
            
*Protocol Registration is open from 8:30 AM - 4:00 PM, Monday-Friday. 
 
4. Fax/e-mail ALL eligibility source documents with registration. Patients will not be 
registered without all required supporting documents. 
Note: If labs were performed at an outside institution, provide a printout of the results. 
Ensure that the most recent lab values are sent. 
 
To complete the registration process, the Registrar will:   
 
• 
assign a patient study number 
• 
register the patient on the study 
• 
assign the patient to treatment arm  
5.0 
Study Outcomes and Study Measures 
5.1 
Primary Outcome 
 
5.1.1 Presence/absence of germinal centers (GCs) in resected cancer tissues 
from patients who receive neoadjuvant vitamin A and controls. 
 
5.2 
Secondary Outcomes 
5.2.1 Measurement of GCs per unit area in adjacent lymph nodes will be 
assessed using semi-quantitative designation (high, moderate, low, or 
absent) in patients who receive neoadjuvant vitamin A and controls. 
 
5.2.2 Pathologic response will be defined by tumor necrosis which will be 
dichotomized as present or absent in patients who receive neoadjuvant 
vitamin A and controls. 
 
5.2.3 Overall survival of patients receiving neoadjuvant Vitamin A and in 
controls.  
 
 
5.3  
Exploratory Outcomes 
 
5.3.1 Immunophenotypic changes among monocytes including quantification of 
MDSCs in pre- and post-treatment blood and tissue samples. Peripheral 
blood samples at 2 time points (before treatment, and after treatment. 
Treatment Plan 
 
 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
 
 
                                              Page 12 of 43 
5.3 
Study-Related Interventions  
 
 
 
 
 
Pre-Studya 
 
After completion  
of Vitamin A 
 
Post-Operative 
 
Informed consent 
 
X 
 
 
 
 
Demographics 
 
X 
 
 
 
 
Medical history 
 
X 
 
 
 
 
Concurrent meds 
 
X 
 
 
 
 
Physical exam 
 
X 
 
 
 
 
Vital signs 
 
X 
X 
 
 
 
Performance Status 
 
X 
 
 
 
 
B-HCGd 
 
X 
 
 
 
Adverse event evaluation 
 
 
X 
 
X 
Research Blood Drawe 
 
X 
X 
 
 
GC Measurement 
 
 
X 
a:  Pre-study requirements listed in table must be completed within 28 days prior to registration.  The 
research blood draw should be collected prior to starting Vitamin A. 
b: Additional monitoring interventions may be done per the treating physician depending on which 
treatment is being given post-assignment. 
c:  Alkaline phosphatase, total bilirubin, BUN, calcium, creatinine, SGOT[AST], SGPT[ALT] 
d:  Serum pregnancy test (women of childbearing potential). 
e:  This procedure is only applicable for patients who chose to participate in the research blood draw 
5.4 
Treatment Administration 
 
Patients who are randomized to receive Vitamin A may start no later than 3 
months from the time of registration in a time frame that allows them to have 
surgery with 10 days of completing treatment Vitamin A treatment.  Vitamin A will 
be administered at 10,000 IU orally for 7 consecutive days. Surgery may occur 
on the day that the last Vitamin A dose is taken.  If surgery is delayed more than 
21 days from completing Vitamin A, the patient will be considered non-evaluable 
and will be replaced. 
6.2.1 Dose Modifications 
 
No dose modifications will be performed.  Patients who have 
unacceptable side effects or withdraw consent prior to undergoing 
surgical resection will discontinue treatment, considered non-evaluable, 
and will be replaced. 
 
 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
 
 
                                              Page 13 of 43 
6.3 
General Concomitant Medication and Supportive Care 
Guidelines 
 
Patients should receive full supportive care, including transfusions of blood and 
blood products, erythropoietin, antibiotics, antiemetics, etc., as clinically 
indicated. Anti-inflammatory or narcotic analgesics may be offered as needed. 
Medications considered necessary for the patient's well-being may be given at 
the discretion of the investigator, i.e., chronic treatments for concomitant medical 
conditions, as well as agents required for life-threatening medical problems, etc. 
The reason(s) for treatment, dosage, and dates of treatment should be recorded 
on the flow sheets.  
6.4 
Duration of Therapy 
 
Treatment will continue for 7 days.  In the absence of treatment delays due to 
adverse events, treatment may continue until one of the following criteria applies: 
 
• 
Disease progression, 
• 
Intercurrent illness that prevents further administration of treatment, 
• 
Unacceptable adverse event(s), specifically if Grade 3 or 4 toxicity is 
observed 
• 
Patient decides to withdraw from the study, or 
• 
General or specific changes in the patient's condition render the 
patient unacceptable for further treatment in the judgment of the 
investigator. 
6.5 
Duration of Follow Up 
 
Patients will be followed for a minimum of 30 days after the last study drug is 
administered for adverse events monitoring. Patients will be followed for a 
minimum of 30 days after removal from study or until death, whichever occurs 
first. Patients removed from study for unacceptable adverse events will be 
followed until resolution or stabilization of the adverse event. Patients will be 
followed until death for monitoring survival study endpoints. 
7.0 
Measurement of Effect 
7.1.1 Methods for Pathologic Evaluation  
 
 
 
 
Standard pathologic evaluation will be performed following surgical 
resection.  This evaluation includes measurement of lymph node 
involvement as well as assessment of histopathologic changes such as 
necrosis within the tumor.  This will be classified as present or absent for 
the purposes of statistical comparison. 
7.1.2 Assessment for efficacy 
Germinal center formation has been observed in 35% of lung cancers 
with the majority of these occurring at the tumor margin.  In the clinical 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
 
 
                                              Page 14 of 43 
laboratory and the laboratory of Dr. Marini, IHC will be performed to 
assess the microenvironment components using an IHC panel.  GCs will 
be assessed as being present or absent and the density GCs at within 
lymph nodes will be estimated using standard digital microscopy and 
automated methods under the supervision of Dr. Marini and Dr. Mikhailov.  
If necessary, manual assessment of GC density within lymph nodes will 
be performed and graded as high, moderate, low, or absen8.0
 
Adverse Events List and Reporting Requirements 
8.1 
Adverse Event List for Vitamin A 
 
Check with your doctor immediately if any of the following side effects 
occur while taking vitamin A: 
• 
Bleeding from gums or sore mouth 
• 
bulging soft spot on head (in babies) 
• 
confusion or unusual excitement 
• 
diarrhea 
• 
dizziness or drowsiness 
• 
double vision 
• 
headache (severe) 
• 
irritability (severe) 
• 
peeling of skin, especially on lips and palms 
• 
vomiting (severe) 
 
Check with your doctor as soon as possible if any of the following side 
effects occur while taking vitamin A: 
• 
Bone or joint pain 
• 
convulsions (seizures) 
• 
drying or cracking of skin or lips 
• 
dry mouth 
• 
fever 
• 
general feeling of discomfort or illness or weakness 
• 
headache 
• 
increased sensitivity of skin to sunlight 
• 
increase in frequency of urination, especially at night, or in amount 
of urine 
• 
irritability 
• 
loss of appetite 
• 
loss of hair 
• 
stomach pain 
• 
unusual tiredness 
• 
vomiting 
• 
yellow-orange patches on soles of feet, palms of hands, or skin 
around nose and lips 
8.2 
Adverse Event Characteristics 
 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
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                                              Page 15 of 43 
• 
CTCAE term (AE description) and grade:  The descriptions and grading 
scales found in the revised NCI Common Terminology Criteria for Adverse 
Events (CTCAE) version 5.0 will be utilized for AE reporting. All appropriate 
treatment areas should have access to a copy of the CTCAE version 5.0. A 
copy of the CTCAE version 5.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov). 
 
• 
‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ (see Section 7.1 
above) for expedited reporting purposes only.   
 
• 
Attribution of the AE: 
 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE is doubtfully related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
8.4 
DSMC SAE Reporting Requirements 
 
The Data Safety and Monitoring Committee (DSMC) is responsible for reviewing SAEs 
for CCCWFU Institutional studies as outlined in Appendix C. DSMC currently requires 
that all unexpected 4 and all grade 5 SAEs on these trials be reported to them for 
review. All CCCWFU Clinical Research Management (CRM) staff members assisting a 
Principal Investigator in investigating, documenting and reporting an SAE qualifying for 
DSMC reporting are responsible for informing a clinical member of the DSMC as well as 
the entire committee via the email notification procedure of the occurrence of an SAE.  
8.5  
WFUHS IRB AE Reporting Requirements 
 
Any unanticipated problems involving risks to subjects or others and adverse events 
shall be promptly reported to the IRB, according to institutional policy. Reporting to the 
IRB is required regardless of the funding source, study sponsor, or whether the event 
involves an investigational or marketed drug, biologic or device. Reportable events are 
not limited to physical injury, but include psychological, economic and social harm. 
Reportable events may arise as a result of drugs, biological agents, devices, procedures 
or other interventions, or as a result of questionnaires, surveys, observations or other 
interactions with research subjects. 
 
All members of the research team are responsible for the appropriate reporting to the 
IRB and other applicable parties of unanticipated problems involving risk to subjects or 
others. The Principal Investigator, however, is ultimately responsible for ensuring the 
prompt reporting of unanticipated problems involving risk to subjects or others to the 
IRB. The Principal Investigator is also responsible for ensuring that all reported 
unanticipated risks to subjects and others which they receive are reviewed to determine 
whether the report represents a change in the risks and/or benefits to study participants, 
and whether any changes in the informed consent, protocol or other study-related 
documents are required. 
 


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Any unanticipated problems involving risks to subjects or others occurring at a site 
where the study has been approved by the WFUHS IRB (internal events) must be 
reported to the WFUHS IRB within 7 calendar days of the investigator or other members 
of the study team becoming aware of the event. 
 
Any unanticipated problems involving risks to subjects or others occurring at another site 
conducting the same study that has been approved by the WFUHS IRB (external 
events) must be reported to the WFUHS IRB within 7 calendar days of the investigator 
or other members of the study team becoming aware of the event. 
 
Any event, incident, experience, or outcome that alters the risk versus potential benefit 
of the research and as a result warrants a substantive change in the research protocol or 
informed consent process/document in order to insure the safety, rights or welfare of 
research subjects. 
9.0 
Pharmaceutical Information 
 
 
A list of the adverse events and potential risks associated with the commercial agent 
administered in this study can be found in Section 8.0. 
9.1 
Pharmaceutical Accountability 
 
All drugs used in this protocol are commercially available.  
9.2 
Vitamin A  
 
Product Description: Vitamin A is provided as retinyl palmitate in 10,000 IU 
capsules from Major Pharmaceuticals. 
 
Storage:  
Vitamin A stock bottles will be purchased and stored in the investigational 
pharmacy.  Temperature conditions will be monitored per standard practice.  
Unopened vials of Vitamin A are stable until the expiration date indicated on the 
package when stored at controlled room temperature. 
 
Route of Administration: Oral 
Drug Accountability:  Patients will be asked to record the time and date of 
medication self-administration with form attached in Appendix. 
 
Disposal: Dispose through the Institutional waste stream and guidelines. 
 
 


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10.0 Data Management 
 
Informed consent document 
EPIC 
Protocol registration form (Appendix A) 
WISER/OnCore 
Baseline Tobacco Use (Appendix D) 
WISER/OnCore  
Adverse Events Log (Appendix E) 
WISER/OnCore  
Outcomes Data Collection (Appendix F) 
WISER/OnCore 
Survival Form (Appendix G) 
WISER/OnCore 
11.0 Statistical Considerations 
 
11.1 Power and Sample Size 
 
Roughly 35% of lung cancers express germinal centers (GC) with the majority of 
GCs being detected at the tumor margin.  Given our target sample size of n=90 
patients per arm, we will have 80% power, using a one-tailed alpha of 0.05, to 
detect an increase to 53% expressing GCs in the treatment arm, given the 
expected “background” 35% in the standard-of-care arm. Given the current 
surgical volume, it is estimated that we will enroll 90 patients per year, so that 
total accrual will last approximately 2 years.  
11.2 Method of Randomization 
 
Patients will be randomized in a 1:1 ratio to receive the vitamin A treatment 
intervention or standard of care.  Patients will be stratified for randomization 
based on pre-operative stage (stage 1, 2, or 3). 
11.3 Analysis of Primary Objective 
 
 
11.3.1 The outcome for our primary objective is dichotomous—GCs 
present/absent. Following basic bivariate analysis in contingency tables of 
presence/absence by treatment arm we will model presence/absence of GCs in a 
logistic regression model as a function of treatment arm, stage, and age at 
diagnosis.  We will first examine the statistical interaction term between stage 
and treatment arm, and if it is significant, we will present findings stratified by 
stage.  If it is not significant, we will remove the interaction term from the final 
model and include stage as a simple covariate only.  
 
11.4  Analysis of secondary objectives 
 
11.4.1 Number of GCs per unit area in lymph nodes will be quantified ordinally 
only, in mutually exclusive ordered groups of high, moderate, low, or absent.  We 
will examine association between treatment arm and rank order of number of 
GCs in contingency table analysis using methods that incorporate the ordinal 
ranking of one of the variables.  We will also model the outcome of rank order of 
number of GCs as a function of treatment arm, age, and stage using ordinal 
logistic regression. As above we will first examine whether there is a significant 


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interaction between stage and treatment arm with respect to the outcome, and if 
so will present findings stratified by stage.   
 
11.4.2 Presence/absence of necrosis will be analyzed in a similar manner as the 
dichotomous outcome of presence/absence of GCs, described above under 
11.3.1. 
 
11.4.3 Overall survival will be estimated in treatment and control groups using 
standard Kaplan-Meier life table analyses and will also be evaluated in the 
multivariable setting using Cox proportional hazards modeling, where covariates 
of age and stage will be included. As described above we will first examine 
whether the statistical interaction between stage and treatment arm is significant.   
11.5 Analysis of Exploratory Objective 
Analyses of changes in lymphocytes will be exploratory in nature.  Changes in T 
regulatory cell concentrations and MDSCs will be assessed in each arm (Dr. 
Triozzi).  These measures will be compared longitudinally between groups using 
a mixed models approach with subjects being considered as random effects and 
time and treatment and time by treatment interaction considered as fixed effects.  
For these analyses the baseline (pre-treatment) assessment of each outcome 
will be included as a covariate in the mixed model.   
 
11.6 Estimated Accrual Rate 
 
 
90  patients per year. 
 
11.7 Estimated Study Length 
Approximately 2 years of accrual plus 6 months for follow-up on last patient and 
data analysis for a total of 2.5 years. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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References 
 
1. 
Sporn MB, Dunlop NM, Newton DL, Smith JM. Prevention of chemical carcinogenesis by 
vitamin A and its synthetic analogs (retinoids). Fed Proc 1976; 35:1332-8.. 
 
2. 
Dragnev KH, I Pitha-Rowe, Y Ma, WJ Petty, D Sekula, B Murphy, M Rendi, N Suh, MB 
Sporn, SJ Freemantle, and E Dmitrovsky. Specific chemopreventive agents trigger 
proteasomal degradation of G1 cyclins: Implications for combination therapy. Clin 
Cancer Res 2004; 10:2570-7.   
 
3. 
Dragnev KH, WJ Petty, and E Dmitrovsky.  Retinoid targets in cancer therapy and 
prevention.  Cancer Biol Ther 2003; 2:S150-6.   
 
4. 
Petty WJ, KH Dragnev, and E Dmitrovsky. Cyclin D1 as a target for chemoprevention. 
Lung Cancer 2003; 41:S155-61.  
 
5. 
Pitha-Rowe I, WJ Petty, Q Feng, PH Koza-Taylor, DA DiMattia, L Pinder, KH Dragnev, N 
Memoli, VA Memoli, T Turi, J Beebe, S Kitareewan, and E Dmitrovsky. Expression 
profiling uncovers UBE1L as a target for lung cancer chemoprevention. Cancer 
Research 2004; 64:8109-8115.   
 
6. 
Dragnev KH, WJ Petty, JR Rigas, and E Dmitrovsky.  Non-classical retinoids and lung 
carcinogenesis.  Clin Lung Cancer. 2005; 6:237-44.  
 
7. 
Petty WJ, N Li, A Biddle, Y Ma, R Bounds, NB Desai, KH Dragnev, S Freemantle, and E 
Dmitrovsky. A novel RARβ isoform and retinoid resistance in lung carcinogenesis. J Natl 
Cancer Inst 2005; 97:1645-51.   
 
8. 
Novotny JA, Harrison DJ, Pawlosky R, Flanagan VP, Harrison EH, Kurilich AC. Beta-
carotene conversion to vitamin A decreases as the dietary dose increases in humans. J 
Nutr. 2010; 140:915-8. 
 
9. 
Wang XD, Liu C, Bronson RT, Smith DE, Krinsky NI, Russell M. Retinoid signaling and 
activator protein-1 expression in ferrets given beta-carotene supplements and exposed 
to tobacco smoke. J Natl Cancer Inst 1999; 91:60-6. 
 
10. 
van Zandwijk N, Dalesio O, Pastorino U, de Vries N, van Tinteren H. EUROSCAN, a 
randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer 
or lung cancer. For the EUropean Organization for Research and Treatment of Cancer 
Head and Neck and Lung Cancer Cooperative Groups. J Natl Cancer Inst 2000; 92:977-
86. 
 
11. 
Goodman GE, Thornquist MD, Balmes J, Cullen MR, Meyskens FL Jr, Omenn GS, 
Valanis B, Williams JH Jr. The Beta-Carotene and Retinol Efficacy Trial: incidence of 
lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping 
beta-carotene and retinol supplements. J Natl Cancer Inst 2004; 96:1743-50. 
 
12.  
Albanes D, Heinonen OP, Huttunen JK, Taylor PR, Virtamo J, Edwards BK, Haapakoski 
J, Rautalahti M, Hartman AM, Palmgren J, et al. Effects of alpha-tocopherol and beta-


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                                              Page 20 of 43 
carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene 
Cancer Prevention Study. Am J Clin Nutr 1995; 62:1427S-1430S. 
 
13. 
Lillenbaum R. (2018). Lung cancer chemoprevention. In T. Post (Ed.) UpToDate. 
Waltham, Mass.: UpToDate. Retrieved from www.uptodate.com 
 
14. 
Dragnev KH, WJ Petty, S Shah, WC Nugent, LD Lewis, CC Black, V Memoli, JR Rigas, 
and E Dmitrovsky.  A proof-of-principle clinical trial of bexarotene in non-small cell lung 
cancer. Clin Cancer Res 2007; 13:1794-1800.   
 
15. 
Yifan Ma and A. Catharine Ross. Toll-Like Receptor 3 Ligand and Retinoic Acid 
Enhance Germinal Center Formation and Increase the Tetanus Toxoid Vaccine 
Response. Clinical and Vaccine Immunology 2009; 16:1476–1484.  
 
16. 
Elizabeth B. Gottlin, Rex C. Bentley, Michael J. Campa, David S. Pisetsky, James E. 
Herndon II, and Edward F. Patz, Jr. The Association of Intratumoral Germinal Centers 
with Early-Stage Non-small Cell Lung Cancer. Journal of Thoracic Oncology 2011;  
6:1687-1690. 
 
 
 
 


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


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Appendix B – Subject Eligibility Checklist 
 
IRB Protocol No. ___ ___ ___ ___ ___ ___ ___ ___  
CCCWFU Protocol No.62218 
Study Title: A Pilot Study of Neoadjuvant Vitamin A for Resectable Non-Small Cell Lung Cancer 
Principal Investigator: W. Jeffrey Petty, MD  
 
Inclusion Criteria 
(as outlined in study protocol) 
Criteria 
is met 
Criteria is 
NOT met 
Source Used to 
Confirm * 
Patient must be >18 years of age 
 
 
 
Patients must have biopsy proven or 
radiographically suspected non-small cell lung 
cancer. 
□ 
□ 
 
Patients must have disease in the chest that is felt 
to be surgically resectable. 
□ 
□ 
 
ECOG performance status of 0-2 
□ 
□ 
 
Ability to understand and the willingness to sign an 
IRB-approved informed consent document 
 
 
 
Exclusion Criteria 
(as outlined in study protocol) 
Criteria 
NOT 
present 
Criteria is 
present 
Source Used to 
Confirm * 
Patients <18 years of age 
 
 
 
Women who are pregnant or breast feeding. 
□ 
□ 
 
Patients may not be receiving any other 
investigational agents for the treatment of NSCLC 
□ 
□ 
 
Patients may not bne taking the following 
medications: high dose vitamin A supplement 
(multivitamin supplements prohibited only if vitamin 
A content is greater than 3,500 IU), bexarotene, 
alitretinoin, tretinoin, adapalene, isotretinoin, 
acetretin, doxycycline, minocycline or 
demeclocycline 
□ 
□ 
 
Uncontrolled intercurrent illness including, but not 
limited to ongoing or active infection, symptomatic 
congestive heart failure, unstable angina pectoris, 
cardiac arrhythmia, or psychiatric illness/social 
situations that would limit compliance with study 
requirements 
□ 
□ 
 
Hypervitaminosis A – toxic effects of ingeting too 
much vitamin A 
□ 
□ 
 
This subject is      
 eligible /  ineligible     for participation in this study. 
 
WISER Assigned PID: __________________ 
 
 
 
 
 
 
 
 
 
Signature of research professional confirming eligibility:_______________________  
Date: ___ ___/___ ___/___ ___ 
 
Signature of Treating Physician:  _____________________________________  


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Date:  ___ ___/___ ___/___ ___ 
 
Signature of Principal Investigator**:  _____________________________________  
Date:  ___ ___/___ ___/___ ___ 
 
* Examples of source documents include clinic note, pathology report, laboratory results, etc. When listing the source, 
specifically state which document in the medical record was used to assess eligibility. Also include the date on the 
document. Example: “Pathology report, 01/01/14” or “Clinic note, 01/01/14” 
 
**Principal Investigator signature can be obtained following registration if needed 
 
 


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Appendix C – Mandatory DSMC SAE Reporting Guidelines 
 
Data and Safety Monitoring Committee 
(DSMC) Serious Adverse Event (SAE) 
Notification SOP 
     Date: 02/11/2021 
 
 
Mandatory DSMC SAE Reporting Requirements in WISER 
This document describes reporting requirements of adverse events from WFBCCC 
Investigator Initiated interventional trials to the Data and Safety Monitoring Committee 
(DSMC). A trial is considered a WFBCCC Investigator Initiated interventional trial if the 
following criteria are met: 
 
1) The Principal Investigator (PI) of the trial is a member of a department at the 
Wake Forest University Baptist Medical Center. 
2) WFBCCC is considered as the primary contributor to the design, implementation 
and/or monitoring of the trial. 
3) The trial is designated as “Interventional” using the Clinical Research 
Categories definitions provided by the NCI in the Data Table 4 
documentation. 
(https://cancercenters.cancer.gov/GrantsFunding/DataGuide#dt4) 
 
There are two distinct types of WFBCCC Investigator Initiated interventional trials based 
on where patient enrollment occurs.  These include: 
 
1) Local WFBCCC Investigator Initiated interventional trials defined as trials where all 
patients are enrolled from one of the WFBCCC sites. These include the main 
outpatient Cancer Center clinics (located in Winston-Salem) as well as WFBCCC 
affiliate sites located in Bermuda Run (Davie Medical Center), Clemmons, 
Lexington, High Point, or Wilkesboro. 
2) Multi-Center WFBCCC Investigator Initiated interventional trials defined as trials 
where patients are enrolled from other sites in addition to WFBCCC sites.   
There are three types of trials that are included in this category: 
a. Trials sponsored by the NCI Community Oncology Research Program 
(NCORP) that are conducted at multiple sites where the PI is a member of a 
department at the Wake Forest University Baptist Medical Center. 
b. Trials sponsored by Industry that are conducted at multiple sites and the 
PI is a member of a department at the Wake Forest University Baptist 
Medical Center. 
c. Trials sponsored by WFBCCC that are conducted at multiple sites and the 
PI is a member of a department at the Wake Forest University Baptist 
Medical Center. 
 
All Adverse Events (AEs) and Serious Adverse Events (SAEs) that occur on any patients 


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


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


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13. Adverse Event Details – Enter all details for each AE associated with the SAE. 
a. Course start date 
b. Category 
c. AE Detail 
d. Comments 
e. Grade/Severity 
f. Unexpected Y/N 
g. DLT Y/N 
h. Attributions 
i. Action 
j. Therapy 
k. Click ADD to attach the AE Detail to the SAE. 
14. Enter Date Notified DSMC -- *This is required for the email notification to be sent* 
15. Click Submit. The auto-generated notification email will disseminate within 5 minutes. 
If you do not receive an email within 5 minutes, check that you have entered the 
“Date Notified DSMC” and the “SAE Classification”. If these have been entered and 
the email still has not been received, take a screen shot of the SAE in WISER and 
immediately email it out to all of the STRC members listed in this SOP. In the subject 
line, indicate that this is a manual transmission of the SAE in lieu of the auto-
generated email. It is required that a notification goes to the DSMC members 
immediately so that their assessment can be obtained within the 24 hour period 
requirement. Contact the Cancer Center Programmer/Analyst to alert that there is an 
issue with the auto-generated email. 
 
The Clinical Members of DSMC to Notify by Phone or Page: 
 
Monday 
Tuesday 
Wednesday Thursday 
Friday 
Saturday Sunday 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu Seegars 
 
Glenn Lesser, MD – Hematology Oncology 
  
Mercedes Porosnicu, MD-- Hematology Oncology 
 
Ryan Hughes, MD – Radiation Oncology
 
Michael Goodman, MD -- Hematology Oncology
 /
 
Daniel Reed, MD -- Hematology Oncology
 
Mary Beth Seegars, MD -- Hematology Oncology 
 
 
 
Definition of Unavailable: 
As a general guideline if the first clinician that is contacted does not respond to the phone 
call or page within 30 minutes, then initiate contact with the next DSMC clinician listed in the 


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table above on the particular day the SAE is being reported. Allow up to 30 minutes for the 
new DSMC clinician to respond to a phone call or page before contacting the next member in 
the table. These times (30 minutes) are a general guideline. Best judgment as a clinical 
research professional should be used giving considerations of the time of day, severity of the 
SAE, and other circumstances as to when it is appropriate to contact backup clinicians. If the 
event occurs near the end of day, then leave messages (voice or email) as appropriate and 
proceed with submitting the DSMC notification form. It is important to take reasonable steps 
and to document that some type of contact has been initiated to one or more of the clinical 
members of DSMC. 
 
DSMC CLINICAN RESPONSIBILITY: 
It is the responsibility of the DSMC clinician to review all reported events, evaluate the events 
as they are reported; and communicate a response to the Investigator, event reporter and 
the members of DSMC. The review will include but not be limited to the information 
reported; there may be times when additional information is needed in order for an 
assessment to be made and further communication directly with the investigator may be 
warranted. DSMC reserves the right to disagree with the Investigator's assessment. If DSMC 
does not agree with the Investigator, DSMC reserves the right to suspend the trial pending 
further investigation. If there is any immediate danger or harm that could be present for a 
future patient based on the information provided in the DSMC report then an immediate 
suspension of enrollment should be considered. 
 
 
AMENDMENTS TO PREVIOUS REPORTS 
If all pertinent information is unavailable with the initial submission, once the additional 
information is available do not submit a new report. Rather, go to the original email that 
was sent to the DSMC and using that email “reply to all”. Entitle this new email 
“Amendment for (list date of event and patient ID)” this will avoid duplications of the same 
event. List the additional information being reported. This information needs to be entered 
into WISER as well. To do this, go to the Subject console and click SAEs on the left column. 
Click on the appropriate SAE number that needs updating. Then click Update. This will allow 
additional  information to be added. 
 
Acronyms 
AE – Adverse Event 
DSMC-Data and Safety Monitoring Committee 
SAE-Serious Adverse Event 
WFBCCC – Wake Forest Baptist Comprehensive Cancer Center 
NCI-National Cancer Institute 
WISER –Wake Integrated Solution for Enterprise Research 
 
 
 
 


A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 05/18/21 
 
 
                                              Page 29 of 43 
 
Screen Shots: 
 
The following screen shots come from the SAE Console within the Subject Console in WISER. 
Screen Shot 1: 
 
Screen Shot 2:
 
 
 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 30 of 43 
Screen Shot 3: 
 
 
 
Screen Shot 4: 
 
 
 
 
 
 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 31 of 43 
Appendix D – Baseline Tobacco Use 
 
CASE REPORT STUDY FORM FOR PATIENT TOBACCO USE 
TO BE USED AT BASELINE 
 
Study Number: 6 2 2 1 8 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: W. Jeffrey Petty, M.D.     
Date: ___ ___/___ ___/___ ___ 
 
Research Personnel Filling out form________________________________________  
 
CANCER PATIENT TOBACCO USE QUESTIONNAIRE (C-TUQ) 
 
Please answer the following questions. This information is 
confidential and will not be shared with your medical providers. 
 
Section 1. Basic Tobacco Use Information 
1. Have you smoked at least 100 cigarettes (5 packs=100 cigarettes) in your 
entire life? 
 
☐ Yes 
☐ No Go to Section 2 (page 2). 
☐ Don’t know/Not sure Go to Section 2 (page 2). 
 
2. How many total years have you smoked (or did you smoke) cigarettes? 
Do not count any time you may have stayed off cigarettes. 
 
_____ Years If you smoked less than one year, write “1.” 
 
3. On average when you have smoked, about how many cigarettes do you 
(or did you) smoke a day? 
 
A pack usually has 20 cigarettes in it. 
 
_____ Number of cigarettes per day 
 
4. How long has it been since you last smoked a cigarette (even one or two 
puffs)? 
 
First check which one of the following choices applies to you. Then, if applicable, 
write a number on the line for how many days, weeks, months, or years it has 
been since your last cigarette. 
☐ I smoked a cigarette today (at least one puff). 
☐ 1-7 days. Number of days since last cigarette: _____ 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 32 of 43 
☐ Less than 1 month. Number of weeks since last cigarette: _____ 
☐ Less than 1 year. Number of months since last cigarette: _____ 
☐ More than 1 year. Number of years since last cigarette: _____ 
☐ Don’t know/Don’t remember 
 
5. In the past 30 days, have you smoked any cigarettes, even one or two 
puffs? 
 
☐ Yes 
☐ No → Go to Question 7. 
 
6. In the past 30 days, have you been trying to quit (or trying to stay off) 
smoking cigarettes? 
 
☐ Yes 
☐ No  
 
Section 2. Use of Other Products 
7. Which of the following products have you ever used regularly? 
 
Check all that apply. 
 
☐ Cigarettes 
☐ E-cigarettes or other electronic nicotine delivery system 
☐ Traditional cigars, cigarillos or filtered cigars 
☐ Pipes 
☐ Hookah 
☐ Clove cigarettes or kreteks 
☐ Bidis 
☐ Smokeless tobacco, like dip, chew, or snuff 
☐ Snus 
☐ Paan with tobacco, gutka, zarda, khaini 
☐ None 
☐ Other, Please specify: _______________________ 
 
8. In the past 30 days, which of the following products have you used? 
 
Check all that apply. 
 
☐ Cigarettes 
☐ E-cigarettes or other electronic nicotine delivery system 
☐ Traditional cigars, cigarillos or filtered cigars 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 33 of 43 
☐ Pipes 
☐ Hookah 
☐ Clove cigarettes or kreteks 
☐ Bidis 
☐ Smokeless tobacco, like dip, chew, or snuff 
☐ Snus 
☐ Paan with tobacco, gutka, zarda, khaini 
☐ None 
☐ Other, Please specify: _______________________ 
 
Section 3. Second-Hand Smoke Exposure 
9. Are you currently living with a smoker? 
☐  Yes 
☐  No 
 
10. In the past 30 days, have you… 
 
 
Yes 
No 
a. Lived in a place where other people 
smoked cigarettes indoors? 
☐ 
☐ 
b. Worked in a place where other 
people smoked cigarettes indoors? 
☐ 
☐ 
 
11. Thinking of all your childhood and adult years, have you ever lived in a 
place where 
other people smoked cigarettes indoors? 
 
☐ Yes →In total, for about how many years? ____ If less than 1, write “1.” 
☐ No 
 
12. Thinking of all the years you have worked, have you ever worked in a 
place where 
other people smoked cigarettes indoors? 
 
☐ Yes →In total, for about how many years? ____ If less than 1, write “1.” 
☐ No 
Thank you for completing this questionnaire. 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 34 of 43 
Appendix E – Adverse Events Log 
 
Patient:  ________________________ 
MRN:  _______________________ 
 
PID:  __________________________ 
Cycle/Start Date:  _______________________ 
 
 
 
 
 
 
ADVERSE EVENT 
CTC Term Version 5.0 
LAB 
VALUE 
GRADE: 
START/STOP DATE: 
ATTRIBUTION: 
1=Definite 
2=Probable 
3=Possible 
4=Unlikely 
5=Unrelated 
EXPECTED: 
N=No 
Y=Yes 
ACTION TAKEN: 
No=None 
DR=Dose reduced 
RI=Regimen interrupted 
TD=Therapy discontinued 
INTR=Interrupted then 
reduced 
SAE: 
N=No 
Y=Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator Signature/Date:  __________________________________________________ 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 35 of 43 
Appendix F – Outcomes Data Collection Form 
 
Instructions: Use this form to collect data related to necrosis and number of germinal centers.  
 
Study Number: ___ ___ ___ ___ ___ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: W. Jeffrey Petty, M.D.     
Date: ___ ___/___ ___/___ ___ 
 
1. Necrosis:  Present 
 Not Present 
 
2. Germinal centers in tumor:  Present 
 Not Present 
a. Location:  
i. Intratumoral_____(Y/N)  
ii. At margins______(Y/N) 
 
3. Density of germinal centers in lymph nodes: 
  High 
 Moderate   Low  
 Not Present 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 36 of 43 
Appendix G – Survival Form 
WISER PID: __ __ __ __ __ __ __ __  
 
Date Completed: __ __ / __ __ / __ __ 
 
PI: ____________________Study Number: 6 2 2 1 8 
Date of 6 Month Follow Up:___ ___ / ___ ___ / ___ ___ 
Name of person completing form __________________________ 
Follow Up: 
 Phone Call to patient 
Phone call with family member who verified patient is alive 
 Patient completed office visit follow up 
 Patient completed office visit at another facility 
Comments: 
______________________________________________________________________________
______________________________________________________________________________ 
Is this subject still living? Yes 
   No 
   Unknown 
 
If the subject has expired, list date of death: ___ ___ / ___ ___ / ___ ___ 
 
 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 37 of 43 
Appendix H – Exploratory Outcomes Data Collection Form 
 
Instructions: Use this form to collect data related to the exploratory aims.  
 
Study Number: _6__ _2__ _2__ _1__ _8__ PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: W. Jeffrey Petty, M.D.     
Date: ___ ___/___ ___/___ ___ 
 
 
1. Lymphocyte count: ______________________________ 
 
2. T regulatory cell concentration: _____________________________ 
 
3. MDSC: _____________________________ 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 38 of 43 
Appendix I– Medical History 
Study Number: _6__ _2__ _2__ _1__ _8__ PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: W. Jeffrey Petty, M.D.     
Date: ___ ___/___ ___/___ ___ 
Instructions: Fill this form out to capture Medical History 
 
1. Medical Comorbidities 
 Acute Myocardial Infarction 
 History of Myocardial Infarction 
 Congestive Heart Failure 
 Peripheral Vascular Disease 
 Cerebrovascular Disease  
 Chronic Obstructive Pulmonary Disease (COPD) 
 Dementia 
 Paralysis (Hemiplegia or Paraplegia) 
 Diabetes 
 Diabetes with Complications 
 Renal Disease 
 Mild Liver Disease 
 Moderate/Severe Liver Disease 
 Peptic Ulcer Disease 
 Rheumatologic Disease 
 AIDS 
(Additional) 
_________________________________________________________________________
___________________________________________________________________ 
 
2. Concurrent medications 
a. List all prescription and over-the-counter medications. For PRN, circle “yes” or “no.”     
Medication Name 
Is it PRN? 
Medication Name 
Is it PRN? 
1. 
yes          no 11. 
yes         no 
2. 
yes          no 12. 
yes         no 
3. 
yes          no 13. 
yes         no 
4. 
yes          no 
 
14. 
yes         no 
5. 
yes          no 
 
15. 
yes         no 
6. 
yes          no 
 
16. 
yes         no 
7. 
yes          no 
 
17. 
yes         no 
8. 
yes          no 
 
18. 
yes         no 
9. 
yes          no 
 
19. 
yes         no 
10. 
yes          no 
 
20. 
yes         no 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 39 of 43 
Appendix J – Vitals Form 
Study Number: _6__ _2__ _2__ _1__ _8__ PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: W. Jeffrey Petty, M.D.     
Date: ___ ___/___ ___/___ ___ 
Instructions: Fill this form out at the baseline/pre-study visit, and after completion of Vitamin A 
 
Study Visit: 
 
 Pre-study 
 After completion of Vitamin A 
 Post Operative 
 
1. Height (inches): ___ ___ 
 
 
2. Weight (lbs): ___ ___ ___  
 
3. BSA: (Calculated using Mosteller’s equation) 
 
4. BMI: (Calculated) 
 
5. Temperature (oF): ___ ___ ___.___ 
a. Route: ______________ 
 
6. Blood Pressure  
a. Systolic (mmHg): ___ ___ ___  
b. Diastolic (mmHg): ___ ___ ___ 
 
7. Heart Rate (beats per minute): ___ ___ ___ 
 
8. Pulse Ox: ___ ___% 
 
9. Respiratory Rate (breaths per minute): ___ ___ 
 
10. ECOG Status:  
 
  0:  Fully active, able to carry on all pre-disease performance without 
restriction. 
 
  1:  Restricted in physically strenuous activity but ambulatory and able to carry 
out work of a light or sedentary nature, e.g., light house work, office work.  
 
  2:  Ambulatory and capable of all self-care but unable to carry out any work 
activities. Up and about more than 50% of waking hours. 
 
  3:  Capable of only limited self-care. Confined to bed or chair more than 50% 
of waking   hours. 
 
  4:  Completely disabled. Cannot carry on any self-care. Totally confined to 
bed or chair. 
 
  5:  Dead 
 
 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 40 of 43 
Vitals Form – page 2 
 
11. Allergies 
 
 
 
 
 
 
 
 
 
 


 
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Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 41 of 43 
Appendix K - Withdrawal of consent for the intervention and medical 
record use 
 
Study Number: ___ ___ ___ ___ ___ PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
PI: ____________________________ Date (mm/dd/yyyy): ___ ___/___ ___/___ ___ ___ ___ 
 
Instructions:  
 
•         I withdraw consent for further study intervention/treatment. 
Yes   
No Initials: ______ 
  
•         I withdraw from further research activities (surveys, questionnaires, research assessments and 
other non-invasive research activities). 
Yes   
No Initials: ______ 
  
•         I withdraw my consent to allow the further collection of research-related information from my 
medical record to be used in this research project. 
Yes  
No Initials: ______ 
 Specimen collection/use withdrawal ( no research specimen collection, skip section) 
I withdraw my consent for any use of my specimen for this current research.  
Yes 
 No Initials: ______ 
I withdraw my consent for any use of my specimen for future research. 
Yes 
No Initials: ______ 
 I acknowledge that any data or deidentified materials that have already been created from my specimen 
may still be used for research.  Initials: ______ 
Patient signature: ________________________________    Date (mm/dd/yy): ___ ___/___ ___/___ ___ 
Investigator signature: _____________________________ Date(mm/dd/yy): ___ ___/___ ___/___ ___ 
 
Comments: 
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________ 
 
 
 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 42 of 43 
Appendix L - Vitamin A Medication Log 
 
Patient Name: _________________________________   Study ID: 62218-____ ____ ____ ____ 
Number of Pills Given: ______                                         Pill Bottle(s) returned: Circle Yes or No 
Total Daily Dose: 10,000 IU  
 
 
              Number of Pills Returned: ______ 
PLEASE FILL OUT AND BRING THIS SHEET AT YOUR NEXT VISIT 
SPECIAL INSTRUCTIONS 
1. Take Vitamin A capsule by mouth for 7 consecutive days. 
2. Log the date and time dose is taken each day. 
3. If a dose is missed, please note the reason under comments. 
4. Remember to bring any unused medication back at the next visit. 
Day 
Medication 
Date 
Time 
Number of 
Pills 
Taken 
Comments 
Example 
Vitamin A 
01/01/2019 
9:00 
AM 
1 
 
 
1 
Vitamin A 
 
 
 
 
 
 
2 
Vitamin A 
 
 
 
 
 
 
3 
Vitamin A 
 
 
 
 
 
 
4 
Vitamin A 
 
 
 
 
 
 
5 
Vitamin A 
 
 
 
 
 
 
6 
Vitamin A 
 
 
 
 
 
 
7 
Vitamin A 
 
 
 
 
 
 
 
Patient Signature: __________________________________  Date: ______________________ 
 
Study Team Signature: ______________________________ Date: ______________________ 
 
Comments: 
______________________________________________________________________________ 
______________________________________________________________________________ 
 


 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62218 
 
Protocol version date 02/04/21 
 
                                                               Page 43 of 43 
Appendix M – Pre-Toxicity  
OnCore PID: __ __ __ __ __ __ __ __  
 
Date Completed: __ __ / __ __ / __ __ 
PI:_W. Jeffery Petty, MD_______________ 
  
Study Number: _62218 
 
 
 
 
 
 
 
 
 
 
 
Evaluation 
Date  
Onset Date  
Toxicity 
Code 
Grade   
(1-5) per 
CTC  
Lab 
value 
UOM
   
Lower 
Limit 
Normal 
Upper 
Limit 
Normal 
Related to 
Disease 
N=No       
Y=Yes  
Symptom 
Description  
Comments 
_ _/_ _/_ _ 
_ _/_ _/_ _ 
   
   
   
   
 
 
   
   
   
_ _/_ _/_ _ 
_ _/_ _/_ _ 
 
 
 
 
 
 
 
 
 
_ _/_ _/_ _ 
_ _/_ _/_ _ 
   
   
   
   
 
 
   
   
   
_ _/_ _/_ _ 
_ _/_ _/_ _ 
   
   
   
   
 
 
   
   
   
_ _/_ _/_ _ 
_ _/_ _/_ _ 
   
   
   
   
 
 
   
   
   
_ _/_ _/_ _ 
_ _/_ _/_ _ 
   
   
   
   
 
 
   
   
   
_ _/_ _/_ _ 
_ _/_ _/_ _ 
   
   
   
   
 
 
   
   
   
_ _/_ _/_ _ 
_ _/_ _/_ _ 
 
 
 
 
 
 
 
 
 
_ _/_ _/_ _ 
_ _/_ _/_ _ 
 
 
 
 
 
 
 
 
 
_ _/_ _/_ _ 
_ _/_ _/_ _ 
 
 
 
 
 
 
 
 
 
_ _/_ _/_ _ 
_ _/_ _/_ _ 
 
 
 
 
 
 
 
 
 
_ _/_ _/_ _ 
_ _/_ _/_ _ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CTCAE Version 5 - https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf  
 
Version 1/10/18  
 

ICF_002.pdf: 
 
Comprehensive Cancer Center 
CCCWFU 62218 
 
 
 
Section of Hematology and Oncology 
 
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-
Small Cell Lung Cancer 
 
NCT03870529 
Version Date:  02/04/2021 
 
Informed Consent Form to Participate in Research 
William J. Petty, M.D., Principal Investigator 
 


Comprehensive Cancer Center
CCCWFU 62218
Page 1 of 10
Version 02/04/2021
Section of Hematology and Oncology
A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small 
Cell Lung Cancer
Informed Consent Form to Participate in Research
William J. Petty, M.D., Principal Investigator
SUMMARY
You are invited to participate in a research study. The purpose of this research is to find out if 
taking vitamin A increases the number of germinal centers in your tumor and lymph tissues. The 
specific Vitamin A for this study is retinyl palmitate or retinyl palmitate/vitamin a.  Germinal 
centers are areas where cells that make antibodies mature and may be beneficial to patients with 
cancer.  Germinal centers can be found in the tumors of some patients with lung cancer.  Some 
researchers think that having germinal centers in the tumor could improve the immune system’s 
ability to fight lung cancer.  Antibodies are proteins released from the immune system cells that 
are a key part of the immune systems function.  You are invited to be in this study because you 
have either known or suspected non-small cell lung cancer and it is thought that the cancer 
should be removed by surgery. Surgery for you type of cancer is standard of care, the research 
portion of this study is the administration of Vitamin A. Your participation in this research will 
involve 2 visits and last from about 2 months to about 3-1/2 months depending upon the timing 
of the surgery. 
Participation in this study will involve taking vitamin A for 7 days. Within the next 21 days you 
will have your surgery.  All research studies involve some risks.  A risk to this study that you 
should be aware of is that vitamin A taken in higher doses can cause bleeding gums, sore mouth, 
bone pain, seizures, dry lips and mouth, diarrhea, double vision and headache.  It is unlikely that 
you will benefit from participation in this study.  
Your participation in this study is voluntary.  You do not have to participate in this study if you 
do not want to.  There may be other choices available to you.  Some other choices may include 
surgery without vitamin A addition.  You will not lose any services, benefits, or rights you would 
normally have if you choose not to participate. 
The remainder of this form contains a more complete description of this study. Please read this 
description carefully. You can ask any questions if you need help deciding whether to join the 
study. The person in charge of this study is William J. Petty, M.D.  If you have questions, 
suggestions, or concerns regarding this study or you want to withdraw from the study his contact 
information (phone number) is: 
. 
If you have any questions, suggestions or concerns about your rights as a volunteer in this 
research, contact the Institutional Review Board at 
 or the Research Subject 
Advocate at Wake Forest at
.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00050640
Meeting Date Approved 1/19/2021          
Version Valid Until: 1/18/2022


Comprehensive Cancer Center
CCCWFU 62218
Page 2 of 10
Version 02/04/2021
INTRODUCTION
You are invited to be in a research study. Research studies are designed to gain scientific 
knowledge that may help other people in the future. You are being asked to take part in this 
study because you have suspected non-small cell lung cancer and it is thought that the cancer 
should be removed by surgery. Your participation is voluntary. Please take your time in making 
your decision as to whether or not you wish to participate. Ask your study doctor or the study 
staff to explain any words or information contained in this informed consent document that you 
do not understand. You may also discuss the study with your friends and family.
WHY IS THIS STUDY BEING DONE?
The purpose of this research is to find out if taking vitamin A increases the number of germinal 
centers in your tumor and lymph tissues. Germinal centers are areas where immune cells that 
make antibodies mature and may be beneficial to patients with cancer. 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
180 people at this research site, Wake Forest Baptist Hospital, will take part in this study.
WHAT IS INVOLVED IN THE STUDY?
During your routine care you will be identified in the clinic as a potential participant in the study. 
If you appear to be eligible you will be screened to make sure you meet all of the study patient 
criteria and then give this document to review and provide your consent. 
You will be randomized into one of the study groups described below. Randomization means 
that you are put into a group by chance. It is like flipping a coin. You will have an equal chance 
of being placed in any group.
Both Groups
Regardless of the group you are in you will have your surgery as a part of your standard care. 
This means you would have this surgery even if you were not on the study. Once your tumor and 
lymph node is removed, we will use part of it to evaluate including measurement of lymph node 
involvement as well as assessment of histopathologic changes. No extra procedures or tissue will 
be removed in this research study to perform the research. 
You will also give blood for research purposes during screening and after completion of Vitamin 
A.
Vitamin A group
If you are randomized into the vitamin A group, you will take vitamin A for 7 days before your 
surgery. You must have your surgery within the next 21 days after your last dose of vitamin A. 
You will be asked to keep track of when you take the vitamin A. After you are finished taking 
your vitamin A you will give a blood sample, have your vital signs taken and discuss any side 
effects you have had. 
If you take part in this study, you will have the following tests and procedures:
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00050640
Meeting Date Approved 1/19/2021          
Version Valid Until: 1/18/2022


Comprehensive Cancer Center
CCCWFU 62218
Page 3 of 10
Version 02/04/2021
Vitamin A Administration
If you are in the vitamin A group you will take vitamin A for a week (7 days) before your 
surgery. This would normally not be done and is for research purposes.
Control Group
If you are randomized into the control group you will not take vitamin A. 
Blood drawing
You will have approximately 2 tablespoons of blood withdrawn from a vein 2 times. The total 
amount of blood withdrawn during the study will be approximately 4 tablespoons. These blood 
draws are for research purposes.
STORAGE OF BIOLOGICAL TISSUE
If you agree to participate in this study, we will draw about 2 tablespoons of blood at two (2) 
separate times for a total of 4 tablespoons to use for future research.  This sample will be kept 
and may be used in future research to learn more about other diseases.  Your sample will be 
obtained in the Cancer Center, clinic, or pre-operative area at Wake Forest University Baptist 
Medical Center. The sample will be stored in the laboratory of Dr. Pierre Triozzi and it will be 
given only to researchers approved by Dr. W. Jeffrey Petty.  An Institutional Review Board 
(IRB) must also approve any future research study using your tissue sample.  
Your blood sample will be stored de-identified, which means that no identifying information will 
be stored with it. Researchers will not know the name, date of birth, medical record number, 
social security number, etc., of the person who donated the sample.
The research that may be performed with your blood sample is not designed to help you 
specifically. There is no personal benefit to you from taking part in this aspect of the research 
study. It might help people who have diseases at some point in the future, but it is not known if 
this will happen. The results of the research performed with your blood will not be given to you 
or your doctor. The results will not be put in your medical record. The research using your blood 
sample will not affect your care.
Your blood sample will be used only for research and will not be sold. The findings from this 
research may result in the future development of products that are of commercial value. There 
are no plans to share any of the profits with you which may occur as a result of the research.
I agree to participate in the optional blood draw as described above.  
_____  YES
_____  NO 
__________ -Participant Initial
In the future, people who do research may need to know more about your health. While the study 
investigator may give reports about your health, he/she will NOT be given your name, address, 
phone number, or any other identifying information about who you are, unless you agree to be 
contacted in the future.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00050640
Meeting Date Approved 1/19/2021          
Version Valid Until: 1/18/2022


Comprehensive Cancer Center
CCCWFU 62218
Page 4 of 10
Version 02/04/2021
____YES you many contact for future research studies
____NO I do not want to be contacted regarding future research studies.
HOW LONG WILL I BE IN THE STUDY?
You will be in the study for up to about 3 months. You will be followed for approximately 30 
days after your last dose of vitamin A to ensure you are not having any unwanted side effect 
from vitamin A.  After that you will be followed for a minimum of 30 days after removal from 
study or until death, whichever occurs first.
WHAT ARE THE RISKS OF THE STUDY?
Being in this study involves some risk to you. You should discuss the risk of being in this study 
with the study staff. The risks associated with your surgery will be described to you by your 
physician and/or surgeon. The risks and side effects directly related to this study are taking 
vitamin A and undergoing blood draws.  Side effects from vitamin A at this dose and duration of 
treatment are uncommon.  With longer durations of vitamin A treatment some people have 
experienced side effects, listed below:
Risk of Vitamin A
Check with your doctor immediately if any of the following side effects occur 
while taking vitamin A:

Bleeding from gums or sore mouth

confusion or unusual excitement

diarrhea

dizziness or drowsiness

double vision

headache (severe)

irritability (severe)

peeling of skin, especially on lips and palms

vomiting (severe)

convulsions (seizures)

fever
Check with your doctor as soon as possible if any of the following side effects 
occur while taking vitamin A:

Bone or joint pain

drying or cracking of skin or lips

dry mouth

general feeling of discomfort or illness or weakness

headache

increased sensitivity of skin to sunlight

increase in frequency of urination, especially at night, or in amount of 
urine

irritability

loss of appetite
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
loss of hair

stomach pain

unusual tiredness

vomiting
There is no evidence that vitamin A is effective for treating or preventing lung cancer.  Some 
similar medications are used to treat other forms of cancer while other similar medications may 
actually increase cancer risk.
In addition, there is a slight risk of a breach of confidentiality.  We will do our best to protect 
your confidential information.  There also may be other side effects that we cannot predict. You 
should tell the research staff about all the medications, vitamins and supplements you take and 
any medical conditions you have. This may help avoid side effects, interactions and other risks.
Risks of Blood Draws
You may experience discomfort, bruising and/or bleeding where the needle is inserted. 
Occasionally some people become dizzy lightheaded or feel faint. Infection may occur on rare 
occasions.  Frequent donation of blood can result in low iron in your blood (iron deficient 
anemia).
Risks of Providing Confidential or Private Information
Taking part in this research study may involve providing information that you consider 
confidential or private.  Efforts, such as coding research records, keeping research records secure 
and allowing only authorized people to have access to research records, will be made to keep 
your information safe.
REPRODUCTIVE RISKS AND OTHER ISSUES TO PARTICIPATING IN RESEARCH
Due to known risks and potential harm to the unborn fetus, sexually active women of 
childbearing potential must use a reliable method of birth control while participating in this 
study. Reliable methods of birth control are: abstinence (not having sex), oral contraceptives, 
intrauterine device (IUD), DepoProvera, tubal ligation, or vasectomy of the partner (with 
confirmed negative sperm counts) in a monogamous relationship (same partner). An acceptable, 
although less reliable, method involves the careful use of condoms and spermicidal foam or gel 
and/or a cervical cap or sponge. We encourage you to discuss this issue further with your 
physicians if you have any questions.
Pregnant women are excluded from participation in this study. If you are a sexually active 
woman of childbearing potential and have not been using a reliable method of birth control, a 
negative pregnancy test is required prior to starting treatment.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
This research is not expected to directly benefit individual subjects, but is likely to yield 
generalizable knowledge.
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WHAT OTHER CHOICES ARE THERE?
This is not a treatment study.  Your alternative is to not participate in this study.
The most common procedure for this condition is surgical resection alone and the risks of 
surgery include pain in the chest, infection, and problems with lung function as well as other 
risks which should be discussed with your surgeon.
WHAT ARE THE COSTS?
All study costs, including any study medications and procedures related directly to the study, will 
be paid for by the study. Costs for your regular medical care, which are not related to this study, 
will be your own responsibility.
WILL YOUR RESEARCH RECORDS BE CONFIDENTIAL?
The results of this research study may be presented at scientific or medical meetings or published 
in scientific journals.  Your identity and/or your personal health information will not be disclosed 
unless it is authorized by you, required by law, or necessary to protect the safety of yourself or 
others.  There is always some risk that even de-identified information might be re-identified. 
Participant information may be provided to Federal and other regulatory agencies as required.  
The Food and Drug Administration (FDA), for example, may inspect research records and learn 
your identity if this study falls within its jurisdiction.
The purpose of this research study is to obtain data or information on the safety and/or 
effectiveness of vitamin A; the results will be provided to the sponsor, the Food and Drug 
Administration and other federal and regulatory agencies as required.
This research is covered by a Certificate of Confidentiality from the National Institutes of 
Health. The researchers with this Certificate may not disclose or use information, documents, or 
biospecimens that may identify you in any federal, state, or local civil, criminal, administrative, 
legislative, or other action, suit, or proceeding, or be used as evidence, for example, if there is a 
court subpoena, unless you have consented for this use. Information, documents, or 
biospecimens protected by this Certificate cannot be disclosed to anyone else who is not 
connected with the research except, if there is a federal, state, or local law that requires 
disclosure (such as to report child abuse or communicable diseases but not for federal, state, or 
local civil, criminal, administrative, legislative, or other proceedings, see below); if you have 
consented to the disclosure, including for your medical treatment; or if it is used for other 
scientific research, as allowed by federal regulations protecting research subjects. 
The Certificate cannot be used to refuse a request for information from personnel of the United 
States federal or state government agency sponsoring the project that is needed for auditing or 
program evaluation by the National Institutes of Health which is funding this project or for 
information that must be disclosed in order to meet the requirements of the federal Food and 
Drug Administration (FDA).  You should understand that a Certificate of Confidentiality does 
not prevent you from voluntarily releasing information about yourself or your involvement in 
this research. If you want your research information released to an insurer, medical care 
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provider, or any other person not connected with the research, you must provide consent to allow 
the researchers to release it.
WILL YOU BE PAID FOR PARTICIPATING?
You will receive no payment for taking part in this study. However, your parking will be 
validated for study-related visits.
The findings from this research may result in the future development of products that are of 
commercial value. There are no plans to provide you with financial compensation or for you to 
share in any profits if this should occur.
WHO IS SPONSORING THIS STUDY?
This study is being sponsored by Wake Forest Baptist Comprehensive Cancer Center. The 
sponsor is providing money or other support to Wake Forest University Health Sciences to help 
conduct this study. The researchers do not, however, hold a direct financial interest in the 
sponsor or the product being studied.
WHAT HAPPENS IF YOU EXPERIENCE AN INJURY OR ILLNESS AS A 
RESULT OF PARTICIPATING IN THIS STUDY?
Should you experience a physical injury or illness as a direct result of your participation in this 
study, Wake Forest University School of Medicine maintains limited research insurance 
coverage for the usual and customary medical fees for reasonable and necessary treatment of 
such injuries or illnesses. To the extent research insurance coverage is available under this policy 
the reasonable costs of these necessary medical services will be paid, up to a maximum of 
$25,000. Wake Forest University Baptist Medical Center holds the insurance policy for this 
coverage. It provides a maximum of $25,000 coverage for each claim and is limited to a total of 
$250,000 for all claims in any one year. The Wake Forest University School of Medicine, and 
the North Carolina Baptist Hospitals, Incorporated do not assume responsibility to pay for these 
medical services or to provide any other compensation for such injury or illness. Additional 
information may be obtained from the Medical Center’s Director of Risk and Insurance 
Management, at 
.
If you are injured, the insurer may require information such as your name, social security 
number, and date of birth in order to pay for your care.  This is because the insurer is required by 
law to report any payments made to cover the care of any persons who are members of a 
government insurance plan to the Department of Health and Human Services.
You do not give up any legal rights as a research participant by signing this consent form. For 
more information on medical treatment for research related injuries or to report a study related 
illness, adverse event, or injury you should call William J. Petty, M.D. at
.
WHAT ABOUT MY HEALTH INFORMATION?
In this research study, any new information we collect from you and/or information we get from 
your medical records or other facilities about your health or behaviors is considered Protected 
Health Information. The information we will collect for this research study includes: results from 
clinical laboratory tests or exams and demographic information. 
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If this research study involves the diagnosis or treatment of a medical condition, then Protected 
Health Information collected from you during this study will be placed in your medical record, 
and may be used to help treat you, arrange payment for your care, or assist with Medical Center 
operations
We will make every effort to keep your Protected Health Information private. We will store 
records of your Protected Health Information in a cabinet in a locked office or on a password 
protected computer. 
Your personal health information and information that identifies you (“your health information”) 
may be given to others during and after the study. This is for reasons such as to carry out the 
study, to determine the results of the study, to make sure the study is being done correctly, to 
provide required reports and to get approval for new products.  
Some of the people, agencies and businesses that may receive and use your health information 
are the research sponsor; representatives of the sponsor assisting with the research; investigators 
at other sites who are assisting with the research; central laboratories, reading centers or analysis 
centers; the Institutional Review Board; representatives of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital; representatives from government agencies such as 
the Food and Drug Administration (FDA) or the Office of Human Research Protections (OHRP), 
the Department of Health and Human Services (DHHS) and similar agencies in other countries.  
Some of these people, agencies and businesses may further disclose your health information. If 
disclosed by them, your health information may no longer be covered by federal or state privacy 
regulations.  Your health information may be disclosed if required by law. Your health 
information may be used to create information that does not directly identify you. This 
information may be used by other researchers. You will not be directly identified in any 
publication or presentation that may result from this study unless there are photographs or 
recorded media which are identifiable.
Monitors, auditors, IRB or other regulatory agencies will be granted direct access to the 
participant’s original medical record for verification of clinical trial procedures or data, without 
violating confidentiality of the participant and to the extent permitted by other applicable laws.
If required by law or court order, we might also have to share your Protected Health Information 
with a judge, law enforcement officer, government agencies, or others. If your Protected Health 
Information is shared with any of these groups it may no longer be protected by federal or state 
privacy rules.
Any Protected Health Information collected from you in this study that is maintained in the 
research records will be kept for at least six years after the study is finished. At that time any 
research information not already in your medical record will either be destroyed or it will be de-
identified. Any research information entered into your medical record will be kept for as long as 
your medical record is kept by the Medical Center. You will not be able to obtain a copy of your 
Protected Health Information in the research records until all activities in the study are 
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completely finished. 
You can tell William J. Petty, M.D. that you want to take away your permission to use and share 
your Protected Health Information at any time by sending a letter to this address:
However, if you take away permission to use your Protected Health Information you will not be 
able to be in the study any longer. We will stop collecting any more information about you, but 
any information we have already collected can still be used for the purposes of the research 
study.
By signing this form you give us permission to use your Protected Health Information for this 
study.
If you choose to participate in this study, your medical record at Wake Forest University Baptist 
Medical Center will indicate that you are enrolled in a clinical trial.  Information about the 
research and any medications or devices you are being given as a participant may also be 
included in your medical record.  This part of the medical record will only be available to people 
who have authorized access to your medical record.  If you are not a patient at this Medical 
Center, a medical record will be created for you anyway to ensure that this important information 
is available to doctors in case of an emergency.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This website will not include information that can identify you.  At most, the 
website will include a summary of the results.  You can search this Web site at any time. 
Laboratory test results and other medical reports created as a result of your participation in the 
research study may be entered into the computer systems of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital.  These will be kept secure, with access to this 
information limited to individuals with proper authority, but who may not be directly involved 
with this research study.
A North Carolina Baptist Hospital (NCBH) medical record will be created for all study 
participants. Information about your participation in the study will be placed in the NCBH 
medical record, along with any routine medical test results that were obtained at NCBH as part 
of this study. 
WHAT ARE MY RIGHTS AS A RESEARCH STUDY PARTICIPANT?
Taking part in this study is voluntary. You may choose not to take part or you may leave the 
study at any time. Refusing to participate or leaving the study will not result in any penalty or 
loss of benefits to which you are entitled. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences. The investigators also have the right to stop your participation in the study 
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at any time. This could be because  it is in your best medical interest, your condition worsened, 
new information becomes available, you had an unexpected reaction, you failed to follow 
instructions, or because the entire study has been stopped. 
You will be given any new information we become aware of that would affect your willingness 
to continue to participate in the study.
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or in the event of a research-related injury, contact the study 
investigator, William J. Petty, M.D. at 
.
The Institutional Review Board (IRB) is a group of people who review the research to protect 
your rights. If you have a question about your rights as a research participant, or you would like 
to discuss problems or concerns, have questions or want to offer input, or you want to obtain 
additional information, you should contact the Chairman of the IRB at 
 or the 
Research Subject Advocate at 
You will be given a copy of this signed consent form. 
SIGNATURES
I agree to take part in this study. I authorize the use and disclosure of my health information as 
described in this consent and authorization form.  If I have not already received a copy of the 
Privacy Notice, I may request one or one will be made available to me.  I have had a chance to 
ask questions about being in this study and have those questions answered.   By signing this 
consent and authorization form, I am not releasing or agreeing to release the investigator, the 
sponsor, the institution or its agents from liability for negligence.
Subject Name (Printed):_____________________________
Subject Signature: _________________________________ Date: ________Time:_______ am pm 
Person Obtaining Consent (Printed):_____________________________
Person Obtaining Consent:___________________________ Date:_________ Time:________ am pm
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00050640
Meeting Date Approved 1/19/2021          
Version Valid Until: 1/18/2022