Conditions: Small Cell Lung Carcinoma Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 14
Healthy volunteers: no

Brief summary:
This phase II pilot trial studies how well gemcitabine and nivolumab work in treating participants with small cell lung cancer that has spread to other parts of the body after other treatments have failed. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving second-line gemcitabine and nivolumab may work better in treating participants with small cell lung cancer.

Detailed description:
PRIMARY OBJECTIVES:

I. To compare response rate (RR) of gemcitabine and nivolumab (G+N) after 4 cycles (8 weeks) to historical controls treated with nivolumab alone.

SECONDARY OBJECTIVES:

I. To compare median overall survival (OS) of G+N to historical controls treated with nivolumab alone.

II. To compare median progression-free survival (PFS) of G+N to historical controls treated with nivolumab alone.

III. To evaluate for tolerability of G+N at each treatment cycle and then every 8 weeks after treatment is completed.

EXPLORATORY OBJECTIVES:

I. To correlate immunophenotypic changes among lymphocytes (quantitative measurements of CD4 and CD8 T-cells) with radiographic response and overall survival before treatment, after treatment and between 8-12 weeks after treatment.

II. Among those patients with tumor mutation burden (TMB) status available, to describe the association between TMB (low, medium, or high) and RR, OS, and PFS.

III. Assess the patient perspective of symptomatic adverse events using self-reported items from the National Cancer Institute (NCI) Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE).

OUTLINE:

Participants receive gemcitabine intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 30 days, 6-10 weeks, and every 8 weeks thereafter.

Arms:
arm 1: Participants receive gemcitabine IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity

Interventions: intervention 1: Gemcitabine intervention 2: Nivolumab
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV

Protocol document:
Prot_SAP_000.pdf: 
Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
 
 
Principal Investigator: 
 
Thomas Lycan, DO 
Hematology & Oncology  
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
tlycan@wakehealth.edu   
336-716-6777 
 
Co-Investigators: 
 
 
W. Jeffrey Petty, MD  
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
wpetty@wakehealth.edu 
336-716-3313 
 
Andy Dothard, MD 
Internal Medicine 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
adothard@wakehealth.edu   
336-716-6777 
 
 
 
 
 
 
Jimmy Ruiz, MD 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
jruiz@wakehealth.edu  
336-716-0490 
 
Stefan C. Grant, MBBCh, MD, JD, MBA, FACP, FACLM 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
scgrant@wakehealth.edu 
336-713-5172 
 
Pierre Triozzi, MD 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
ptriozzit@wakehealth.edu 
336-716-0230 
 
Laurie Steffen, PhD 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
lsteffen@wakehealth.edu 
336-716-7596 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
 
 
Payal Gandhi, PA-C 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
pgandhi@wakehealth.edu 
336-716-0230 
 
Rebecca Kinney, PA-C 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
pgandhi@wakehealth.edu 
336-716-0230 
 
Greg Hawkins, PhD 
Center for Human Genomics 
Wake Forest School of Medicine 
ghawkins@wakehealth.edu 
336-716-0230 
 
Biostatistician: 
 
 
Beverly Levine 
Comprehensive Cancer Center of Wake Forest University 
 
 
 
 
 
blevine@wakehealth.edu 
 
 
 
 
 
336-713-1653 
 
Research Nurse: 
 
 
Sharon Averill 
Comprehensive Cancer Center of Wake Forest University 
saverill@wakehealth.edu 
336-716-0230 
 
 
Data Manager 
 
 
Deonna Asbury 
Comprehensive Cancer Center of Wake Forest University 
dasbury@wakehealth.edu 
336-716-0230 
 
Regulatory Contact: 
 
Cindy Miller 
Comprehensive Cancer Center of Wake Forest University 
cytmill@wakehealth.edu 
336-713-6770 
 
ClinicalTrials.gov: 
 
 
NCT03662074 
 
Participating Institution(s):  
WFBCCC 
 
 
Version Date: 
 
 
05/20/2020  
 
Amended: 
 
 
 
05/20/2020  
 
 
Confidential


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
Page 3 of 52 
Table of Contents 
Schema...................................................................................................................................... 5 
1.0 
Introduction and Background .......................................................................................... 6 
2.0 
Objectives ...................................................................................................................... 8 
2.1 
Primary Objective(s) ................................................................................................... 8 
2.2 
Secondary Objective(s) .............................................................................................. 8 
2.3 
Exploratory Objectives ................................................................................................ 8 
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 ..............................................................................................................12 
6.1 
Study-Related Interventions .......................................................................................12 
6.2 
Treatment Administration ...........................................................................................12 
6.2.1 
Premedication regimen and concurrent medications ............................................13 
6.2.2 
Dose Modifications...............................................................................................13 
6.3 
General Concomitant Medication and Supportive Care Guidelines ............................14 
6.4 
Duration of Therapy ...................................................................................................14 
6.5 
Duration of Follow Up ................................................................................................14 
7.0 
Measurement of Effect ..................................................................................................14 
7.1.1 
Methods for Evaluation of Measurable Disease ...................................................14 
7.1.2 
Response Criteria - RECIST ................................................................................15 
7.1.3 
Assessment for efficacy .......................................................................................15 
7.1.4 
Survival Outcomes ...............................................................................................16 
8.0 
Adverse Events List and Reporting Requirements .........................................................16 
8.1 
Adverse Event List for Gemcitabine ...........................................................................16 
8.2 
Adverse Event List for Nivolumab ..............................................................................16 
8.3 
Adverse Event Characteristics ...................................................................................16 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
Page 4 of 52 
8.4 
STRC SAE Reporting Requirements .........................................................................17 
8.5  
WFUHS IRB AE Reporting Requirements .................................................................17 
9.0 
Pharmaceutical Information ...........................................................................................18 
9.1 
Pharmaceutical Accountability ...................................................................................18 
9.2 
Gemcitabine (Gemzar) ..............................................................................................18 
9.3 
Nivolumab (OPDIVO) ................................................................................................19 
10.0 
Exploratory Studies Collections and Processing ............................................................20 
11.0 
Data Management .........................................................................................................21 
12.0 
Statistical Considerations ..............................................................................................21 
12.1 
Power and Sample Size ............................................................................................21 
12.3 
Analysis of Primary Objective ....................................................................................21 
12.4 
Analysis of Secondary Objectives ..............................................................................22 
12.5 
Analysis of Exploratory Objective...............................................................................22 
12.6 
Estimated Accrual Rate .............................................................................................22 
12.7 
Estimated Study Length .............................................................................................22 
References ...............................................................................................................................23 
Appendix A – Protocol Registration Form ..................................................................................25 
Appendix B – Subject Eligibility Checklist ..................................................................................26 
Appendix C - Race & Ethnicity Verification Form .......................................................................28 
Appendix D – Mandatory STRC SAE Reporting Guidelines ......................................................29 
Appendix E – Baseline Tobacco Use ........................................................................................36 
Appendix F - Tumor Measurement Worksheet ..........................................................................39 
Appendix G – 30 - day Treatment Follow-up Form ....................................................................41 
Appendix H - Adverse Events Log.............................................................................................42 
Appendix I - Survival Data .........................................................................................................43 
Appendix J – Treatment Response Evaluation Form ................................................................44 
Appendix K-Evaluation of Best Overall Response .....................................................................45 
Appendix L – Off-Study Form ....................................................................................................46 
Appendix M – Exploratory Studies Form ...................................................................................48 
Appendix N – PRO CTCAE & Selected FACIT Items ................................................................49 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
Page 5 of 52 
Schema 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
Page 6 of 52 
1.0 
Introduction and Background 
 
Lung cancer (LC) is the third most common cancer in both men and women and the 
leading cause of cancer death, with only 15% of lung cancer cases diagnosed at the 
local stage.1 Small cell lung cancer (SCLC) is a particularly aggressive neuroendocrine 
tumor of the lung that accounts for 13% of all lung cancer histologic types. Overall, there 
is a poor prognosis for advanced lung cancer and a need for novel treatment regimens.  
 
Nivolumab is an IgG4 monoclonal antibody that blocks T-cell programmed cell death 
protein 1 (PD-1) and prevents it from interacting with PD-L1; thus, releasing the brakes 
on autoimmunity and allowing cytotoxic T-cell destruction of tumor cells. For their 2017 
update, the National Comprehensive Cancer Network (NCCN) added nivolumab and the 
combination of nivolumab and ipilumumab as new category 2A options for subsequent 
systemic therapy of advanced SCLC.2 This addition was based on the Checkmate 032 
phase 1/2 trial of SCLC patients, which found a response rate ( ) of 10% for nivolumab 3 
mg/kg; all responses were partial (PR) with no complete responses [CR]; there was also 
another 22% of participants who had stable disease (SD) as best response. Median PFS 
was 1.4 months and median overall survival (OS) was 4.4 months. Single agent 
nivolumab for SCLC had a 6% rate of therapy discontinuation due to treatment-related 
adverse events. The arms, which had combinations of nivolumab and ipilumumab, had 
higher RR (~20%) but with higher toxicity (10% treatment discontinuation) including 
three treatment-related deaths out of 115 participants.3  
 
For comparison, oral topotecan is the only FDA-approved subsequent line therapy for 
relapsed or refractory SCLC with a RR of 51% and median overall survival of six months 
as compared to three months with best supportive care.4 Nivolumab has a lower rate of 
serious grade 3-4 adverse events (5-10%) than oral topotecan and it is typically better 
tolerated. The most common mild symptoms associated with nivolumab are fatigue, 
anorexia, asthenia, nausea, and diarrhea. Immunotherapy is unique from traditional 
cytotoxic chemotherapy due to a risk of autoimmune complications such as pneumonitis, 
colitis, or hypophysitis.5,6 These complications are treated with steroids and reversible if 
recognized in a timely manner but in rare cases can be fatal even after 
immunosuppression.7 
 
Currently, the standard of practice for lung cancer patients treated with nivolumab is to 
assess initial response after four two-week cycles (total eight weeks) and, if there is a 
response, to continue nivolumab alone until there is either progression of disease, 
intolerance, or patient refusal. Assessing treatment response has traditionally been done 
with the Response Evaluation Criteria in Solid Tumors (RECIST) response criteria, with 
partial response defined by the target lesions decreasing in size to less than 70% of their 
original size and the absence of any new lesions.8 SD is defined by traditional RECIST 
criteria as the stability of target lesions between 70% and 120% of their original size and 
with no new lesions noted.8 PD is defined by traditional RECIST criteria as the 
enlargement of target lesions to >120% of their original size or the development of new 
lesions.8  
 
Biomarkers may be predictive of response to immunotherapy for some patients. Tumor 
mutation burden (TMB) is determined by whole-exome sequencing on the tumor and is 
classified by the number of somatic mutations into low (0 to <143), medium (143 to 247), 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
Page 7 of 52 
or high (>248) tertiles. Immunohistochemistry (IHC) with increased PD-L1 expression on 
tumor cells may also be predictive of greater efficacy of nivolumab for non-small cell lung 
cancer (NSCLC).9 However, SCLC has a lower prevalence of PD-L1 expression (~13% 
with ≥1% expression) and presence of PD-L1 did not correlate with response in the 
Checkmate 032 study.3 
 
A relatively new strategy to augment the RR of immune checkpoint inhibitors in lung 
cancer is to combine them with traditional cytotoxic chemotherapy.10 Safety data have 
been demonstrated for other tumor types. The phase I Checkmate 012 study of NSCLC 
patients reported a low rate of early dose-limiting toxicities when nivolumab (10 mg/kg) 
was combined with platinum-doublet chemotherapy, with 21% of participants receiving 
nivolumab/gemcitabine/cisplatin. 11 An abstract of preliminary results from a phase I 
study of squamous NSCLC patients combining nivolumab (10 mg/kg q3 weeks) with 
concurrent gemcitabine (1250 mg/m2) and cisplatin (75 mg/m2) for first-line treatment 
found that 45% of participants across all arms had grade 3/4 toxicities.12 An abstract of 
preliminary results from another phase I study suggested that the addition of nivolumab 
to gemcitabine and nab-paclitaxel in advanced pancreatic cancer was also tolerated 
well.13 These data suggest that the the combination of nivolumab and cytotoxic 
chemotherapy can be safely tested for the treatment of SCLC. 
 
Gemcitabine, an analog of cytidine, which inhibits DNA replication, is a cytotoxic 
chemotherapy that causes cell cycle arrest in tumor cells. This cell stress increases 
cytokine release and up-regulates HLA expression; in turn leading to increased tumor 
cell killing by cytotoxic T-cells14-16 Gemcitabine may have additional mechanisms of 
inducing an immune response against tumors. Gemcitabine has been shown to 
decrease the accumulation of myeloid-derived suppressor cells in cell culture17 and in 
mouse models18-20; removing another potential inhibitor of immunotherapy. 
Immunophenotypic analysis of lymphocytes in the peripheral blood of pancreatic cancer 
patients also found that gemcitabine was associated with decreased memory T-cells 
(CD45RO+) and increased early activated T-cells (CD69+); suggestive that gemcitabine 
may promote naïve T-cell activation.21 In current clinical practice, gemcitabine in 
combination with cisplatin is FDA-approved for the treatment of NSCLC; the 
recommended gemcitabine dosing is either 1000 mg/m2 over 30 minutes on Days 1, 8, 
and 15 of each 28-day cycle or as 1250 mg/m2 over 30 minutes on Days 1 and 8 of each 
21-day cycle.22 These dosing schedules can be difficult to tolerate and in typical clinical 
practice they are often dose-reduced; for example, to 1000 mg/m2 over 30 minutes on 
days 1 and 15 of each 28-day cycle. For relapsed or refractory SCLC, single agent 
gemcitabine is included as a category 2A recommendation by NCCN as it has an 
objective RR of 12% with a median survival of 7 months.2,23 Serious adverse events with 
gemcitabine are uncommon for lung cancer patients and include cytopenias (3-6%), 
nausea/vomiting (6%), dyspnea (5%), infection (1%), and somnolence (1%).24 Rarely, 
serious pulmonary toxicity can occur in <1% of patients; this can include pneumonitis or 
pulmonary edema/fibrosis.25 
 
Nivolumab as a monotherapy has a low RR when used in subsequent line of therapy to 
treat SCLC. However, it may be possible to augment the effect of nivolumab with the 
addition of gemcitabine for both its cytotoxic and tumor immunogenic effects. The safety 
of this combination has already been reported in the phase I CheckMate 012 study of 
nivolumab/gemcitabine/cisplatin.11 This proposed phase 2 study will test for efficacy of 
the addition of gemcitabine to nivolumab (G+N) to see if RR can be increased as 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
Page 8 of 52 
compared to a historical comparison group of SCLC patients who received nivolumab 
alone as part of the Checkmate 032 trial.3  
 
Treatment tolerability, the extent to which adverse effects and other aspects of treatment 
can be tolerated by a patient, is a critical complement to efficacy data. Patients who are 
unable to tolerate treatment experience dose delays or discontinue treatment. Patient 
reported outcomes (PROs) assess subjective tolerability. This may include the extent to 
which patients are bothered by side effects, side effect and symptom severity, and 
functional impact of treatment.26 The National Cancer Institute has developed a library of 
PROs to complement clinician-rated toxicities. These items are intended to be reviewed 
alongside CTCAE grading for a more accurate and comprehensive understanding of 
treatment-related adverse events. These items have demonstrated validity, reliability, 
and sensitivity to change, but do not capture overall health-related quality of life, an 
important subjective component of tolerability.27,28 The Functional Assessment of 
Chronic Illness Therapy (FACIT) system is a PRO measurement system and gold 
standard in evaluating health-related quality of life. Some evidence suggests that a 
single item from this system, “I am bothered by the side effects of treatment,” may 
predict treatment adherence and correlate with clinician-rated AEs.29 This item may be 
an important measure of treatment tolerability in and of itself. Therefore, in an 
exploratory aim, this phase 2 study will assess patient-reported outcome measures of 
adverse events, treatment tolerability, and health-related quality of life.  
2.0 
Objectives 
2.1 
Primary Objective(s) 
 
2.1.1 To compare RR of G+N after 4 cycles (8 weeks) to historical controls 
treated with nivolumab alone. 
2.2 
Secondary Objective(s) 
 
2.2.1 To compare median overall survival (OS) of G+N to historical controls 
treated with nivolumab alone. 
 
2.2.2 To compare median progression-free survival (PFS) of G+N to historical 
controls treated with nivolumab alone. 
 
2.2.3 To evaluate for tolerability of G+N at each treatment cycle and then until 
2-6 weeks after treatment is completed. 
2.3 
Exploratory Objectives 
2.3.1 To correlate immunophenotypic changes among lymphocytes 
(quantitative measurements of CD4 and CD8 T-cells) with radiographic 
response and overall survival before treatment, after treatment and 
between 8-12 weeks after treatment. 
 
2.3.2 Among those patients with TMB status available, to describe the 
association between TMB (low, medium, or high) and RR, OS, and PFS. 
2.3.3 Assess the patient perspective of symptomatic adverse events, treatment 
tolerability, and health-related quality of life using self-reported items from 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
Page 9 of 52 
the NCI Patient Reported Outcomes-Common Terminology Criteria for 
Adverse Events (PRO-CTCAE) and Functional Assessment of Chronic 
Illness Therapy (FACIT).  
3.0 
Patient Selection 
3.1 
Inclusion Criteria  
 
3.1.1 Patients must have histologically or cytologically confirmed incurable 
SCLC and have had prior treatment with platinum-based chemotherapy. 
High-grade neuroendocrine tumors that are suspected to be of 
bronchopulmonary origin can be enrolled if they have had prior treatment 
with a SCLC chemotherapy regimen (e.g. platinum plus etoposide). 
 
 
 
 
 
 
 
3.1.2 Patients should not be demonstrating end-organ damage due to rapid 
progression of disease based on the most recent assessment of the 
treating physician.  
 
3.1.3 Patients must have radiographically measurable metastatic disease by 
RECIST criteria. 
 
3.1.4 ECOG performance status of 0-2. 
 
3.1.5 Patients must have normal organ and marrow function as defined below: 
 
- absolute neutrophil count 
≥1,500/mcL 
- platelets 
≥100,000/mcL 
 
3.1.6 Chemotherapy agents are known to be teratogenic, therefore women of 
child-bearing potential and men must agree to use adequate 
contraception (hormonal or barrier method of birth control) prior to study 
entry and for the duration of study participation. Should a woman become 
pregnant or suspect she is pregnant while participating in this study, she 
should inform her treating physician immediately. 
 
3.1.7 Ability to understand and the willingness to sign an IRB-approved 
informed consent document 
3.2 
Exclusion Criteria  
 
3.2.1 Emergent need for palliative radiation.  
 
3.2.2 Patients may not be receiving any other investigational agents for the 
treatment of SCLC. 
 
3.2.3 History of allergic reaction to gemcitabine. 
 
 
 
3.2.4 Uncontrolled intercurrent illness including, but not limited to ongoing or 
active infection, symptomatic congestive heart failure, unstable angina 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
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pectoris, cardiac arrhythmia, or psychiatric illness/social situations that 
would limit compliance with study requirements. 
 
3.2.5 Pregnant women are excluded from this study because of the potential for 
teratogenic or abortifacient effects with chemotherapy. Because there is 
an unknown but potential risk for adverse events in nursing infants 
secondary to treatment of the mother with chemotherapy, breastfeeding 
should be discontinued. 
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 expected enrolled 
sample size of 60 we plan to enroll at least 20 women. Similarly, we expect 
approximately 5% of study participants to be Hispanic/Latino (N=3). We plan to 
enroll at least 15% Black or African American (N=9), no American Indian/Alaska 
Natives, and 5% Asian (N=3). 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: 
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. 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
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To complete the registration process, the Registrar will:   
 
 
assign a patient study number 
 
register the patient on the study 
5.0 
Study Outcomes and Study Measures 
5.1 
Primary Outcome 
 
5.1.1 Radiographic RR after 4 cycles (8 weeks) of G+N as compared to 
baseline CT scan obtained within 2 weeks prior to cycle 1. 
5.2 
Secondary Outcomes 
 
5.2.1 OS of G+N assessed every 8 weeks from the start of therapy until death 
among all enrolled participants. 
 
5.2.2 PFS of G+N as determined by investigator assessment. Assessed every 
8 weeks from the start of therapy until progression or death among all 
enrolled participants.  
 
5.2.3 Toxicities will be measured using CTC AE version 5.0 at every treatment 
cycle and until 2-6 weeks after treatment is completed. Assessed among 
all enrolled participants.  
 
5.3 
Exploratory Outcomes 
 
5.3.1 Clinical outcomes (RR, OS, PFS) and association with immunophenotypic 
changes among lymphocytes (CD4 vs. CD8). 
 
5.3.2 Clinical outcomes (RR, OS, PFS) and association with TMB (low, 0 to 
<143; medium, 143 to 247; or high, >248). 
 
5.3.3 Descriptive analysis of patient responses to PRO-CTCAE and FACIT 
items. 
 
 
 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
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6.0 
Treatment Plan 
6.1 
Study-Related Interventions  
 
 
 
 
 
Pre-Studya 
 
At Each 
Treatment 
 
While on treatmentb 
Post-
Treatment 
Visit 
Follow-up 
 
Informed consent 
 
X 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
Baseline tobacco 
(Appendix E) 
X 
 
 
 
 
 
Concurrent meds 
 
X 
 
 
 
 
 
 
Physical exam 
 
X 
Xb 
X 
X 
 
 
Vital signs 
 
X 
x 
X 
X 
 
 
Height, Weight, M2 
 
X 
 
 
 
 
 
 
Performance Status 
 
X 
 
 
X 
 
 
Tumor measurements 
X 
 
 
X 
 
 
CBC w/diff, platelets 
 
X 
X 
 
X 
 
 
Serum chemistryc 
 
X 
X 
 
X 
 
 
B-HCGd 
 
X 
 
 
 
 
 
Adverse event evaluationf 
 
 
X 
X 
X 
X 
 
PRO-CTCAE  and selected 
FACIT itemse 
X 
X 
X 
X 
X 
Research Blood Drawg 
X 
 
 
 
X 
X 
a:Pre-study requirements listed in table must be completed within 14 days prior to registration. Scans 
must be done within 28 days prior to registration.. 
b: Physical exam not necessary at every treatment visit. 
c:Alkaline phosphatase, total bilirubin, BUN, calcium, creatinine, SGOT[AST], SGPT[ALT] 
d:Serum pregnancy test (women of childbearing potential). 
e: to be performed at patient preference 
f: There are 3 research blood draws in total. The first “baseline” blood draw will be within 2 weeks prior to 
administration of cycle 1; it can be drawn on the date of first treatment as long as it is collected before 
infusion is started. The second “post-treatment” blood draw should be drawn within 2-4 weeks after 
administration of cycle 4. The third “follow-up” blood draw should be within 6-10 weeks after 
administration of cycle 4. 
   
6.2 
Treatment Administration 
 
Patients who have relapsed or refractory SCLC, have previously had platinum-based 
chemotherapy, and have radiographically measurable metastatic disease will be 
registered and consented.   


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
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Regimen 
The treatment regimen will consist of four - two-week cycles for both gemcitabine and 
nivolumab that will be administered initially as directed below, unless otherwise indicated 
by the treating physician.  
G+N Treatment Regimen:  
 
Day 1of each cycle: 
o Gemcitabine: 1000mg/m2 IV. 
o Nivolumab: 240 mg IV. 
 
Treatment will be repeated every 2 weeks +/- 3 days 
 
Days 2-14: No Treatment 
 
Treatment among all groups will be administered on either an inpatient or outpatient 
basis as per the treating physician. Reported adverse events and potential risks are 
described in Section 8.0. Appropriate dose modifications are described in Section 6.2.2. 
No investigational or commercial agents or therapies other than those described below 
may be administered with the intent to treat the patient's malignancy. 
6.2.1 Premedication regimen and concurrent medications 
 
 
 
 
 
 
 
Anti-emetics: 
Anti-emetics should consist of standard 5HT3 antagonist 
medications at the investigators discretion.  Use of corticosteroids 
as prophylactic anti-emetics should generally be avoided and 
reasons for the use of these drugs as pre-medications should be 
documented. 
6.2.2 Dose Modifications 
 
For nivolumab and gemcitabine, dose adjustments during treatment will 
be made at the investigator’s discretion in accordance with standard 
medical practice.  Reasons for dose interruption and dose reduction must 
be documented.   
 
For non-hematologic toxicities, general guidelines include intervention for 
intolerable grade 2, any grade 3, or any grade 4 toxicities related to 
treatment.  Intervention may include: addition of a medication to 
ameliorate symptoms; temporary suspension of dosing; or dose 
reduction.  
 
For hematologic toxicities, general guidelines include delay in treatment 
for absolute neutrophil count less than 1500 cells/uL or platelet count less 
than 100,000 cells/uL.  Addition of colony stimulating factors (including 
neupogen or neulasta) is allowed at the investigator’s discretion for 
treatment of neutropenia.  
 


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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 
in the medical record.  
6.4 
Duration of Therapy 
 
The duration of the research treatment is through the first follow-up CT scan.  
Treatment may continue beyond this point at the investigator’s discretion.  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 
neurotoxicity 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 have one follow-up assessment (either in clinic or over phone) between 
2-6 weeks (14-42 days) after administration of cycle 4for adverse events 
monitoring. If no clinic visit occurs during this window, a phone call confirmation 
should be made to the patient to determine vital status and whether any adverse 
events and in particular, Grade 4 unexpected adverse events occurred during 
that window of time and recorded on Appendix G. 
7.0 
Measurement of Effect 
 
7.1.1 Methods for Evaluation of Measurable Disease 
 
 
Unscheduled evaluations may be done at the discretion of the 
investigator as needed to assess the subject’s clinical status. 
The imaging technique used for each subject (CT or MRI) is at the 
discretion of the investigator, but the same technique must be used for 


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each individual subject throughout the study. Imaging should not be 
delayed in case of missed doses or dose delays. 
7.1.2 Response Criteria - RECIST 
 
Target Lesions 
At time of each tumor assessment, the response in target lesions is 
defined as follows: 
o Complete Response (CR): Disappearance of all target lesions. 
o Partial Response (PR): Decrease by ≥ 30% in sum of longest 
diameter of target lesions. 
o Stable Disease (SD): Not meeting criteria for CR, PR, or PD. 
o Progressive Disease (PD): Increase by ≥ 20% in sum of longest 
diameter of target lesions or the appearance of one or more new 
lesions. 
 
Response in Non-Target Lesions 
The presence of non-target lesions is established at baseline; at each TA, 
the presence of any new, non-measurable lesions is assessed. The 
presence of new, non-measurable lesions will rule out an overall 
response of CR.  
 
The response in non-target lesions is defined as follows: 
o Complete Response (CR): Complete disappearance of all non-
target lesions. 
o Stable Disease (SD): Persistence of one or more non-target 
lesion(s). 
o Progressive Disease (PD): Appearance of one or more new 
lesions and/or unequivocal progression of existing non-target 
lesions. 
7.1.3 Assessment for efficacy 
RR will be assessed after 4 cycles (8 weeks) of treatment with 
gemcitabine and nivolumab. 
 
The following efficacy parameters will be assessed by independent 
radiology review according to RECIST, and are defined as follows: 
 
Objective RR: the proportion of subjects who achieve complete or partial 
response 
 
Duration of best response: the duration of time from the date 
measurement criteria are first met for CR, or PR (if CR is never met), until 
the first date that PD is confirmed by independent radiology review or 
death, whichever comes first 
 
Disease control rate: the percentage of subjects who achieved CR, PR, or 
SD 
 


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Duration of disease control: the duration of time from the date 
measurement criteria are first met for CR, PR, or SD, until the first date 
that PD is confirmed by independent radiology review or death, whichever 
comes first 
 
Tumor measurement imaging after 4 cycles at 8 weeks +/- 1 week of 
treatment with gemcitabine and nivolumab. 
7.1.4 Survival Outcomes 
 
Progression-Free Survival (PFS) is defined as the duration of time from the start 
of treatment to the time of investigator assessed progression or death. PFS will 
be assessed every 4 cycles (8 weeks) among all registered participants. 
Following the completion of the intervention, PFS will be assessed approximately 
every 8 weeks by chart review. Any participants who are lost to follow up will be 
censored.  
 
Overall Survival (OS) is defined as the duration of time from the start of treatment 
to date of death. OS will be assessed every 4 cycles (8 weeks) among all 
registered participants. Following the completion of the intervention, OS will be 
assessed approximately every 8 weeks by chart review. Any participants who are 
lost to follow up will be censored. 
8.0 
Adverse Events List and Reporting Requirements 
 
8.1 
Adverse Event List for Gemcitabine 
 
Bone marrow suppression is the most common dose-limiting toxicity of 
gemcitabine. Other common side effects include edema, alopecia, rash, 
hyperglycemia, hypomagnesemia, constipation, diarrhea, nausea, vomiting, 
stomatitis, anemia, neutropenia, thrombocytopenia, elevated liver function tests, 
infections, lymphocytopenia, paresthesia, neuropathy, hematuria, proteinuria, 
elevated creatinine, dyspnea, fatigue, and fever. 
 
 
8.2 
Adverse Event List for Nivolumab 
 
Most common adverse reactions have included fatigue, cough, nausea, pruritus, 
rash, decreased appetite, constipation, arthralgia, thyroid function abnormalities, 
and diarrhea. The most frequent serious adverse drug reactions were renal 
failure, dyspnea, and pneumonitis. 
8.3 
Adverse Event Characteristics 
 
 
CTCAE term (AE description) and grade:  The descriptions and grading 
scales found in the revised NCI Common Terminology Criteria for Adverse 
Events (CTCAE) version 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 


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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 
STRC SAE Reporting Requirements 
 
The Safety and Toxicity Reporting Committee (STRC) is responsible for reviewing SAEs 
for CCCWFU Institutional studies as outlined in Appendix D. STRC 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 
STRC reporting are responsible for informing a clinical member of the STRC as well as 
the entire committee via the email notification procedure of the occurrence of an SAE.  
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. 
 
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. 


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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 investigational or 
commercial agents 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 
Gemcitabine (Gemzar) 
 
Product Description: Gemcitabine is supplied in 200 mg and 1000 mg 
vials. Two hundred mg vials are reconstituted in 5 cc sodium chloride then 
diluted to a concentration of as low as 0.1 mg/ml if necessary for infusion. 
The dose is usually 1000 or 1250 mg/m2 given over 30 minutes. One 
thousand mg vials are reconstituted with 25 cc sodium chloride. It is 
stored at room temperature until given. 
 
Preparation:  
Caution should be exercised in handling and preparing Gemzar solutions. The 
use of gloves is recommended. If Gemzar solution contacts the skin or mucosa, 
immediately wash the skin thoroughly with soap and water or rinse the mucosa 
with copious amounts of water. Although acute dermal irritation has not been 
observed in animal studies, 2 of 3 rabbits exhibited drug-related systemic 
toxicities (death, hypoactivity, nasal discharge, shallow breathing) due to dermal 
absorption. 
 
The recommended diluent for reconstitution of Gemzar is 
0.9% Sodium Chloride Injection without preservatives. Due to solubility 
considerations, the maximum concentration for Gemzar upon reconstitution is 40 
mg/mL. Reconstitution at concentrations greater than 40 mg/mL may result in 
incomplete dissolution, and should be avoided. 
 
To reconstitute, add 5 mL of 0.9% Sodium Chloride Injection to the 200-mg vial 
or 25 mL of 0.9% Sodium Chloride Injection to the 1-g vial. Shake to dissolve. 
These dilutions each yield a gemcitabine concentration of 38 mg/mL which 
includes accounting for the displacement volume of the lyophilized powder (0.26 
mL for the 200-mg vial or 1.3 mL for the 1-g vial). The total volume upon 
reconstitution will be 5.26 mL or 26.3 mL, respectively. Complete withdrawal of 
the vial contents will provide 200 mg or 1 g of gemcitabine, respectively. The 


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appropriate amount of drug may be administered as prepared or further diluted 
with 0.9% Sodium Chloride Injection to concentrations as low as 0.1 mg/mL.  
 
Reconstituted Gemzar is a clear, colorless to light straw-colored solution. After 
reconstitution with 0.9% Sodium Chloride Injection, the pH of the resulting 
solution lies in the range of 2.7 to 3.3. The solution should be inspected visually 
for particulate matter and discoloration, prior to administration, whenever solution 
or container permit. If particulate matter or discoloration is found, do not 
administer. 
 
Route of Administration: Intravenous 
 
Storage: Unopened vials of Gemzar are stable until the expiration date indicated 
on the package when stored at controlled room temperature 20° to 25°C (68° to 
77°F). Store at controlled room temperature (20° to 25°C) (68° to 77°F). The 
USP has defined controlled room temperature as “A temperature maintained 
thermostatically that encompasses the usual and customary working 
environment of 20° to 25°C (68° to 77°F); that results in a mean kinetic 
temperature calculated to be not more than 25°C; and that allows for excursions 
between 15° and 30°C (59° and 86°F) that are experienced in pharmacies, 
hospitals, and warehouses. 
 
Stability: When prepared as directed, Gemzar solutions are stable for 24 hours 
at controlled room temperature 20° to 25°C (68° to 77°F). Discard unused 
portion. Solutions of reconstituted Gemzar should not be refrigerated, as 
crystallization may occur. 
 
Disposal: Dispose through the Institutional waste stream and guidelines. 
Nivolumab (OPDIVO) 
 
 
Product description:   
OPDIVO is a clear to opalescent, colorless to pale-yellow solution. Discard 
the vial if the solution is cloudy, discolored, or contains extraneous particulate 
matter other than a few translucent-to-white, proteinaceous particles. 
OPDIVO for injection is supplied at 40 mg/4 mL and 100 mg/10 mL in a single 
use vial. 
Solution preparation:  
Caution should be exercised in handling and preparing OPDIVO for Injection, 
USP. Several guidelines on this subject have been published. To minimize the 
risk of dermal exposure, always wear impervious gloves when handling vials 
containing OPDIVO for Injection, USP. 
 
 
Withdraw the required volume of OPDIVO and transfer into an intravenous 
container.   
 
Dilute OPDIVO with either 0.9% Sodium Chloride 
Injection, USP or 5% Dextrose Injection, USP to prepare 
an infusion with a final concentration ranging from 1 
mg/mL to 10 mg/mL.   


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 
Mix diluted solution by gentle inversion.  
 
Do not shake.   
 
Discard partially used vials or empty vials of OPDIVO 
 
Storage requirements:  
The product does not contain a preservative. 
  
After preparation, store the OPDIVO infusion either:   
 at room temperature for no more than 4 hours from the time of 
preparation. This includes room temperature storage of the infusion in 
the IV container and time for administration of the infusion or  
  
 under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 
hours from the time of infusion preparation.  
 
 Do not freeze. 
 
Stability:   
OPDIVO is stable for no more than 4 hours at room temperature from the time of 
preparation and for no more than 24 hours under refrigeration 2°C-8°C (36°F to 
46°F) 
 
Route of administration:   
Intravenous 
 
Administration   
 
Administer the infusion over 60 minutes through an intravenous line 
containing a sterile, non-pyrogenic, low protein binding in-line filter (pore 
size of 0.2 micrometer to 1.2 micrometer). 
 
Do not co-administer other drugs through the same intravenous line.  
 
 
Use separate infusion bags and filters for each infusion. 
 
Disposal: Dispose through the Institutional waste stream and guidelines. 
10.0 Exploratory Studies Collections and Processing 
 
To address the exploratory objective, 2.3.1, at 3 separate timepoints, blood samples for 
research draw will be obtained for plasma and other biomarker analyses. The first 
“baseline” blood draw will be within 2 weeks prior to administration of cycle 1. The 
second “post-treatment” blood draw will be within 2-4 weeks after administration of cycle 
4. The third “follow-up” blood draw will be within 6-10 weeks after administration of cycle 
4. In most cases, blood testing will be added on to regularly scheduled phlebotomy for 
clinical labs which are drawn as part of routine oncology care. Some participants may 
require an additional blood draw if insufficient blood samples were collected. For the 
purposes of our study, 6 mL of venous blood will be collected in a sodium heparin 
(green-top) collection tube and then transferred directly to Dr. Triozzi’s lab in the 
Department of Cancer Biology for processing per laboratory protocols for downstream 


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analysis. Venous blood will be stored in lab refrigerator prior to transfer (in oncology lab) 
and after transfer (in Dr. Triozzi’s lab) prior to processing and then freezing. Plasma will 
be stored and analyzed by the Genetics Core and Biomedical Engineering laboratories 
at Wake Forest School of Medicine or Dr. Triozzi’s laboratory for future studies that may 
include changes in ctDNA markers (Dr. Greg Hawkins and Dr. Adam Hall). Assessed 
among all enrolled participants as permitted by research funding. . 
 
A patient-reported outcome measures of treatment-related adverse events, treatment 
tolerability, and health-related quality of life will be filled out by patients at patient 
preference.  
11.0 Data Management 
 
Informed consent document 
EPIC 
Protocol registration form 
WISER/OnCore 
Baseline Tobacco Use (Appendix E) 
WISER/OnCore 
Tumor Measurement Form (Appendix F) 
WISER/OnCore  
30 Day Treatment Follow-up Form (Appendix G) 
WISER/OnCore  
Adverse Events Form (Appendix H) 
WISER/OnCore  
Survival Data (Appendix I) 
WISER/OnCore  
Treatment Response Form (Appendix J) 
WISER/OnCore  
Evaluation of Best Response (Appendix K) 
WISER/OnCore 
Off-Study Form (Appendix L) 
WISER/OnCore  
Exploratory Studies Form (Appendix M) 
WISER/OnCore 
PRO-CTCAE and FACIT items (Appendix N) 
WISER/OnCore/REDCap 
12.0 Statistical Considerations 
 
12.1 Power and Sample Size 
Simon's two-stage design (Simon, 1989) will be used. The null hypothesis of the 
historical RR 10% will be tested against a one-sided alternative. In the first stage, 
10 patients will be accrued. Accrual will continue until the first 10 patients have 
either been evaluated for response or withdrawn from the study.  If there is 1 or 
fewer responses in the first10 patients, the study will be stopped and no further 
patients will be accrued’ patients who have already been enrolled on the study 
will complete their treatment per protocol.  If there are 2 or more responses in the 
first 10 patients, 19 additional patients will be accrued for a total of 29. The null 
hypothesis will be rejected if 6 or more responses are observed in 29 patients. 
This design yields a type I error rate of 0.047 and power of 0.8 when the true 
response rate is 30%. 
12.3 Analysis of Primary Objective 
Response by RECIST comparing CT scan at the time of registration to CT scan 
following 4 cycles of treatment. Objective RR (CR+PR) will be compared 
between this study sample and a historical benchmark value of 10%.3 For this 
comparison we will use a one-sample test of proportion.  


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12.4 Analysis of Secondary Objectives 
Overall survival and progression free survival rates will be estimated in our 
sample using standard Kaplan Meier survival analysis methods. Median PFS 
from all participants treated with G+N will be compared to historical control of 
median 1.4 months among 98 participants treated with nivolumab for SCLC. 
Median OS from all participants treated with G+N will be compared to historical 
control of median 4.4 months among 98 participants treated with nivolumab for 
SCLC.3 Toxicity rates will be estimated by responder status and presented 
overall and by body site.  
12.5 Analysis of Exploratory Objective 
Changes in T regulatory cell concentrations will be assessed in each arm (Dr. 
Triozzi).  These measures will be compared longitudinally to examine whether 
changes in certain biomarkers are associated with patients who experience an 
objective response. Peripheral blood samples at 3 time points (baseline before 
study treatment, post-treatment, and at follow-up [between 6 and 10 weeks post-
treatment]) will be analyzed by flow cytometry (flow cytometry core, Dr. Triozzi).  
 
TMB status (low, medium, or high) will be assessed as to how they relate to RR, 
OS, and PFS. This subgroup analysis will be in a descriptive manner only due to 
the small size of the study. 
 
Participants self-reported adverse events (PRO-CTCAE assessment), treatment 
tolerability (FACIT item), and health-related quality of life (FACIT items) will be 
assessed at patient preference; these scores will be reported in a descriptive 
manner only due to the small size of the study. We will also report the numbers 
of participants who were offered and completed this optional measure; this is to 
assess acceptability of obtaining this measure routinely among lung cancer 
participants at this institution.  
 
 
12.6 Estimated Accrual Rate 
We estimate that we will enroll approximately 15 patients per year. Given our 
target completed enrollment of 29 patients, and allowing for 5% drop out, we 
estimate it will take approximately 25 months to enroll 31 patients.   
 
12.7 Estimated Study Length 
Approximately 31 months, allowing for 6 months’ follow-up on last patient. 
 
 


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(Amsterdam, Netherlands). 1998;22(3):243-250. 
25. 
Roychowdhury DF, Cassidy CA, Peterson P, Arning M. A report on serious pulmonary 
toxicity associated with gemcitabine-based therapy. Investigational new drugs. 
2002;20(3):311-315. 
26. 
Pearman TP, Beaumont JL, Mroczek D, O'Connor M, Cella D. Validity and usefulness of 
a single-item measure of patient-reported bother from side effects of cancer therapy. 
Cancer. 2018;124(5):991-997. 
27. 
Dueck AC, Mendoza TR, Mitchell SA, et al. Validity and Reliability of the US National 
Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology 
Criteria for Adverse Events (PRO-CTCAE). JAMA oncology. 2015;1(8):1051-1059. 
28. 
Basch E, Pugh SL, Dueck AC, et al. Feasibility of Patient Reporting of Symptomatic 
Adverse Events via the Patient-Reported Outcomes Version of the Common 
Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy 
Cooperative Group Multicenter Clinical Trial. International journal of radiation oncology, 
biology, physics. 2017;98(2):409-418. 
29. 
Wagner LI, Zhao F, Goss PE, et al. Patient-reported predictors of early treatment 
discontinuation: treatment-related symptoms and health-related quality of life among 
postmenopausal women with primary breast cancer randomized to anastrozole or 
exemestane on NCIC Clinical Trials Group (CCTG) MA.27 (E1Z03). Breast cancer 
research and treatment. 2018;169(3):537-548. 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
Page 25 of 52 
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 (mm/dd/yy): ___ ___ /___ ___/___ ___ 
 
Performance Status: ___  ECOG   
  
Protocol Registrar can be contact by calling 336-713-6767 between 8:30 AM and 4:00 PM, Monday – Friday. 
 
Completed Eligibility Checklist and Protocol Registration Form must be hand delivered, faxed or e-mailed to 
the registrar at 336-713-6772 or registra@wakehealth.edu. 
 
 
 
PROTOCOL INFORMATION 
Date of Registration (mm/dd/yy): 
___ ___ / ___ ___ / ___ ___ 
MD Name (last) : 
______________________       
Date protocol treatment started (mm/dd/yy): ___ ___ / ___ ___ / ___ ___ 
Informed written consent: 
(consent must be signed prior to 
registration) 
 YES  NO 
 
Date Consent Signed (mm/dd/yy): 
___ ___ / ___ ___ / ___ ___ 
 
PID # (to be assigned by OnCore): 
___ ___ ___ ___ ___ ___ ___ ___ 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
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Appendix B – Subject Eligibility Checklist 
 
 
IRB Protocol No. 00051024 
CCCWFU Protocol No.62418 
Study Title: Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced 
SCLC 
Principal Investigator: Thomas Lycan, DO 
 
Inclusion Criteria 
(as outlined in study protocol) 
Criteria 
is met 
Criteria is 
NOT met 
Source Used to 
Confirm * 
Patients must have histologically or cytologically 
confirmed incurable small cell lung cancer and 
have had prior treatment with platinum-based 
chemotherapy. High-grade neuroendocrine 
tumors that are suspected to be of 
bronchopulmonary origin can be enrolled if they 
have had prior treatment with a SCLC 
chemotherapy regimen (e.g. platinum plus 
etoposide). 
□ 
□ 
 
Patients should not be demonstrating end-organ 
damage due to rapid progression of disease 
based on the most recent assessment of the 
treating physician 
□ 
□ 
 
Patients must have radiographically measurable 
metastatic disease by RECIST criteria 
□ 
□ 
 
ECOG performance status of 0-2 
□ 
□ 
 
Absolute neutrophil count >1,500/mcL 
 
□ 
□ 
 
Platelets >100,000/mcL 
 
□ 
□ 
 
Chemotherapy agents are known to be 
teratogenic, therefore women of child-bearing 
potential and men must agree to use adequate 
contraception (hormonal or barrier method of birth 
control) prior to study entry and for the duration of 
study participation. Should a woman become 
pregnant or suspect she is pregnant while 
participating in this study, she should inform her 
treating physician immediately 
□ 
□ 
 
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 * 
Emergent need for palliative radiation 
□ 
□ 
 
Patients may not be receiving any other 
investigational agents for treatment of small cell 
lung cancer 
□ 
□ 
 


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Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
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History of allergic reaction to gemcitabine 
□ 
□ 
 
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. 
□ 
□ 
 
Pregnant women are excluded from this study 
because of the potential for teratogenic or 
abortifacient effects with chemotherapy. Because 
there is an unknown but potential risk for adverse 
events in nursing infants secondary to treatment 
of the mother with chemotherapy, breastfeeding 
should be discontinued 
□ 
□ 
 
 
This subject is      
 eligible /  ineligible     for participation in this study. 
 
OnCore Assigned PID: ___ ___ ___ ___ ___ ___ ___ ___  
 
 
 
 
Signature of research professional confirming eligibility: _______________________  
Date (mm/dd/yy): ___ ___/___ ___/___ ___ 
 
Signature of Treating Physician:  _____________________________________  
Date (mm/dd/yy):  ___ ___/___ ___/___ ___ 
 
Signature of Principal Investigator**:  _____________________________________  
Date (mm/dd/yy):  ___ ___/___ ___/___ ___ 
 
* Examples of source documents include clinic note, pathology report, laboratory results, etc. When listing 
the source, specifically state which document in the medical record was used to assess eligibility. Also 
include the date on the document. Example: “Pathology report, 01/01/14” or “Clinic note, 01/01/14” 
 
**Principal Investigator signature can be obtained following registration if needed 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
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WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
Page 28 of 52 
 
Appendix C - Race & Ethnicity Verification Form 
 
Thank you so much for helping us to verify your race and ethnicity to ensure the quality of our 
information. As a brief reminder, the information you provide today will be kept confidential. 
 
1. Are you: 
Hispanic or Latino/a 
Not Hispanic or Latino/a 
 
2. What is your race? One or more categories may be selected. 
White or Caucasian 
Black or African American 
American Indian or Alaskan Native 
Asian 
Native Hawaiian or Other Pacific Islander 
Other, Please Specify: ___________________________ 
          
    
 
 
 
Internal use only: 
 
 
 Name: ____________________ MRN#: ____________________  
 
Was the self-reported race and ethnicity of the participant verified at the time of consent? 
Yes        No 
 
Was a discrepancy found?       Yes         No 
         If yes, please provide what is currently indicated in the EMR:  
 
 
Ethnicity: ____________________  
Race: ____________________ 
Additional comments: __________________________________________________________________ 
 
__________________________________________________________________ 
 
__________________________________________________________________ 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
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WFBCCC # 62418 
 
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Appendix D – Mandatory STRC SAE Reporting Guidelines 
 
Safety and Toxicity Review Committee 
(STRC) Serious Adverse Event (SAE) 
Notification SOP 
Date: 07/10/2019 
 
Mandatory STRC SAE Reporting Requirements in WISER 
This document describes reporting requirements of adverse events from WFBCCC Investigator 
Initiated interventional trials to the Safety and Toxicity Review Committee (STRC). A trial is 
considered a WFBCCC Investigator Initiated interventional trial if the following criteria are met: 
 
1) The Principal Investigator (PI) of the trial is a member of a department at the Wake Forest 
University Baptist Medical Center. 
2) WFBCCC is considered as the primary contributor to the design, implementation and/or 
monitoring of the trial. 
3) The trial is designated as “Interventional” using the Clinical Research Categories 
definitions provided by the NCI in the Data Table 4 documentation. 
(https://cancercenters.cancer.gov/GrantsFunding/DataGuide#dt4) 
 
There are two distinct types of WFBCCC Investigator Initiated interventional trials based on where 
patient enrollment occurs.  These include: 
 
1) Local WFBCCC Investigator Initiated interventional trials defined as trials where all patients are 
enrolled from one of the WFBCCC sites. These include the main outpatient Cancer Center 
clinics (located in Winston-Salem) as well as WFBCCC affiliate sites located in Bermuda Run 
(Davie Medical Center), Clemmons, Lexington, High Point, or Wilkesboro. 
2) Multi-Center WFBCCC Investigator Initiated interventional trials defined as trials where 
patients are enrolled from other sites in addition to WFBCCC sites.   
There are three types of trials that are included in this category: 
a. Trials sponsored by the NCI Community Oncology Research Program (NCORP) that are 
conducted at multiple sites where the PI is a member of a department at the Wake 
Forest University Baptist Medical Center. 
b. Trials sponsored by Industry that are conducted at multiple sites and the PI is a 
member of a department at the Wake Forest University Baptist Medical Center. 
c. Trials sponsored by WFBCCC that are conducted at multiple sites and the PI is a 
member of a department at the Wake Forest University Baptist Medical Center. 
 
All Adverse Events (AEs) and Serious Adverse Events (SAEs) that occur on any patients enrolled on 
WFBCCC Investigator Initiated Interventional trials must be entered into the WISER system. The only 
exception to this requirement is for patients enrolled on NCORP trials at non- WFBCCC sites. AEs and 
SAEs for NCORP patients enrolled at WFBCCC sites must be entered into the WISER system. Once these 
AEs and SAEs are entered in WISER, certain actions must be taken regarding the reporting of specific 
Adverse Events to the STRC. 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
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WFBCCC # 62418 
 
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All Adverse Events that occur during protocol intervention (defined below) and are coded as either 1) 
unexpected grade 4, 2) unplanned inpatient hospitalization > 24 hours (regardless of grade), or grade 5 
(death) must be reported to the STRC using the using the SAE console in WISER. 
 
A research nurse or clinical research coordinator when made aware that an adverse event meets one of 
the above criteria has occurred on a WFBCCC Investigator Initiated interventional trial, is responsible for 
informing a clinical member of the STRC by phone (or in-person) about the adverse event. The 
nurse/coordinator should contact the treating physician prior to calling the STRC clinical member to 
obtain all details of the SAE, as well as all associated toxicities to be recorded along with the SAE. In 
addition, this nurse or coordinator is responsible for entering the adverse event information into the SAE 
console in WISER.  Once the adverse event has been entered into the SAE console an email informing the 
entire STRC committee will be generated. 
 
THESE REPORTING REQUIREMENTS APPLY TO any staff member on the study team for a WFBCCC Institutional 
Interventional trial. Ultimately, the protocol PI has the primary responsibility for AE identification, documentation, 
grading and assignment of 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 STRC. 
 
What is considered during protocol intervention? 
During protocol intervention is considered to be the time period while a patient is on study treatment or 
during the time period within 30 days of last study treatment (even if patient begins a new (non-study) 
treatment during the 30 days). This window of 30 days should be the standard window to be used in all 
protocols unless a specific scientific rationale is presented to suggest that a shorter window can be used 
to identify events. If it is a trial sponsored by Industry and the sponsor requires a longer window for 
monitoring of SAEs, then the longer window of time specified by the sponsor should be followed. 
 
What is considered as an Unexpected Grade 4 event? 
Any grade 4 event that was not specifically listed as an expected adverse event in the protocol should be 
considered as unexpected. A grade 4 adverse event can be considered to be unexpected if it is an event 
that would not be expected based on the treatment being received or if it is unexpected based on the 
health of the patient. In either case, if there is any uncertainty about whether a grade 4 adverse event is 
expected or unexpected it should be reported to STRC. 
 
STRC notification responsibilities of the person (e.g., nurse) handling the reporting/documenting of the SAE in 
WISER: 
1. Make a phone call (or speak in person) to the appropriate clinical member of the STRC as listed 
below (page if necessary) 
2. Enter a new SAE into the SAE module that is located in the Subject>> CRA Console in WISER 
WITHIN 24 HOURS of first knowledge of the event. Information can be entered and saved, but 
the STRC members will not be notified until a date is entered into the STRC Notification Date 
Field. This will ensure that all persons that need to be made aware of the event (i.e., study team 
members and STRC members) will be notified; remember to file a copy of the confirmation. 
3. Document that the appropriate person(s) on the STRC has been contacted. Indicate the name of 


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WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
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the STRC clinician that was contacted in the Event Narrative field in the SAE console of the 
particular subject. 
4. Document whether or not the protocol should be suspended based on the discussion with the 
STRC clinician. This is the major function of the email notification. Enter whether the protocol 
should be suspended in the Event Narrative Field. 
5. Follow up/update the clinical member(s) of STRC regarding any new developments or information 
obtained during the course of the SAE investigation and reporting process. 
 
Elements needed to complete the SAE form in the Subject Console in WISER (see Screen Shot 3): 
1. Event Date 
2. Reported Date 
3. Reported by 
4. If Grade 5, enter Death Date 
5. If Grade 5, enter Death occurred: within 30 days 
6. Event Narrative: Brief description (include brief clinical history relevant to this event, including 
therapies believed related to event). Begin narrative with the STRC clinician who was notified and 
Date/Time notified. In addition, state attribution by STRC clinician as either “Unrelated”, 
“Unlikely”, “Possibly”, “Probably”, or “Definitely”.  Always include the following here: 
i. STRC clinician name and comments 
ii. Date of last dose before the event 
iii. Is suspension of the protocol needed? Y/N 
7. Treating Physician comments 
8. PI comments, if available 
9. Protocol Attribution after discussion with STRC clinician 
10. Outcome (Fatal/Died, Intervention for AE Continues, Migrated AE, Not Recovered/Not Resolved, 
Recovered/Resolved with Sequelae, Recovered/Resolved without Sequelae, Recovering and 
Resolving) 
11. Consent form Change Required? Y/N 
12. SAE Classification *This is required in order for the email notification to be sent* 
13. Adverse Event Details – Enter all details for each AE associated with the SAE. 
a. Course start date 
b. Category 
c. AE Detail 
d. Comments 
e. Grade/Severity 
f. Unexpected Y/N 
g. DLT Y/N 
h. Attributions 
i. Action 
j. Therapy 
k. Click ADD to attach the AE Detail to the SAE. 
14. Enter Date Notified STRC -- *This is required for the email notification to be sent* 
15. Click Submit. The auto-generated notification email will disseminate within 5 minutes. If you do 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
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WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
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not receive an email within 5 minutes, check that you have entered the “Date Notified STRC” and 
the “SAE Classification”. If these have been entered and the email still has not been received, take 
a screen shot of the SAE in WISER and immediately email it out to all of the STRC members listed 
in this SOP. In the subject line, indicate that this is a manual transmission of the SAE in lieu of the 
auto-generated email. It is required that a notification goes to the STRC members immediately so 
that their assessment can be obtained within the 24 hour time frame requirement. Contact the 
Cancer Center Programmer/Analyst to alert that there is an issue with the auto-generated email. 
 
The Clinical Members of STRC to Notify by Phone or Page: 
Bayard Powell, MD – Director-at-Large, WFBCCC; Section Head, Hematology/Oncology 6-7970 / 
6-2701 / Pager 336-806-9308 
Glenn Lesser, MD – Hematology Oncology 6-9527 / 6-7972 / Pager 336-806-8397  
Stefan Grant, MD, JD-Hematology Oncology 3-5172/ 6-5772 Pager 336-806-6453  
Jimmy Ruiz, MD-Hematology Oncology 6-0230/ Pager 336-806-9710 
Mercedes Porosnicu, MD- Hematology Oncology 6-7980 / 6-0230 / Pager 336-806-9150 
         Michael Farris, MD – Radiation Oncology 3-6540 / 3-6505 Pager 336-806-8541 
 
Definition of Unavailable: 
As a general guideline if the first clinician that is contacted does not respond to the phone call or page 
within 30 minutes, then initiate contact with a different STRC clinician. Allow up to 30 minutes for the 
new STRC clinician to respond to a phone call or page before contacting another member. These times 
(30 minutes) are a general guideline. Best judgment as a clinical research professional should be used 
giving considerations of the time of day, severity of the SAE, and other circumstances as to when it is 
appropriate to contact backup clinicians. If the event occurs near the end of day, then leave messages 
(voice or email) as appropriate and proceed with submitting the STRC notification form. It is important to 
take reasonable steps and to document that some type of contact has been initiated to one or more of 
the clinical members of STRC. 
 
STRC CLINICAN RESPONSIBILITY: 
It is the responsibility of the STRC clinician to review all reported events, evaluate the events as they are 
reported; and communicate a response to the Investigator, event reporter and the members of STRC. The 
review will include but not be limited to the information reported; there may be times when additional 
information is needed in order for an assessment to be made and further communication directly with 
the investigator may be warranted. STRC reserves the right to disagree with the Investigator's 
assessment. If STRC does not agree with the Investigator, STRC reserves the right to suspend the trial 
pending further investigation. If there is any immediate danger or harm that could be present for a future 
patient based on the information provided in the STRC report then an immediate suspension of 
enrollment should be considered. 
 
AMENDMENTS TO PREVIOUS REPORTS 
If all pertinent information is unavailable with the initial submission, once the additional information is 
available do not submit a new report. Rather, go to the original email that was sent to the STRC and 
using that email “reply to all”. Entitle this new email “Amendment for (list date of event and patient ID)” 
this will avoid duplications of the same event. List the additional information being reported. This 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
Page 33 of 52 
 
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 
STRC-Safety and Toxicity Review Committee 
SAE-Serious Adverse Event 
WFBCCC – Wake Forest Baptist Comprehensive Cancer Center 
NCI-National Cancer Institute 
WISER –Wake Integrated Solution for Enterprise Research 
Screen Shots: 
 
The following screen shots come from the SAE Console within the Subject Console in WISER. 
 
Screen Shot 1: 
 
 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC # 62418 
 
Protocol version date 05/20/20 
 
 
 
 
 
Page 34 of 52 
 
Screen Shot 2: 
 
Screen Shot 3: 
 
 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 35 of 52 
 
Screen Shot 4: 
 
 
 
 
 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 36 of 52 
 
Appendix E – Baseline Tobacco Use 
 
Instructions: Case Report Study Form for patient tobacco use to be used at baseline 
 
Study Number: CCCWFU 62418 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Thomas Lycan, DO    
Date(mm/dd/yy): ___ ___/___ ___/___ ___ 
 
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: _____ 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
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CCCWFU # 62418 
 
  
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Page 37 of 52 
 
☐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 


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CCCWFU # 62418 
 
  
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☐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. 
 
 


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CCCWFU # 62418 
 
  
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Page 39 of 52 
 
Appendix F - Tumor Measurement Worksheet 
 
Target Lesions 
TARGET Lesions 
Lesion 
Site 
Imaging 
(ie,CT, MRI) 
Baseline 
Date: 
(Se, Im) 
Cycle_____ 
Date: 
(Se, Im) 
Cycle_____ 
Date: 
(Se, Im) 
Cycle_____ 
Date: 
(Se, Im) 
Cycle_____ 
Date: 
(Se, Im) 
Cycle_____ 
Date: 
(Se, Im) 
01 
 
 
 
mm 
mm 
mm 
mm 
mm 
mm 
02 
 
 
 
mm 
mm 
mm 
mm 
mm 
mm 
03 
 
 
 
mm 
mm 
mm 
mm 
mm 
mm 
04 
 
 
 
mm 
mm 
mm 
mm 
mm 
mm 
05 
 
 
 
mm 
mm 
mm 
mm 
mm 
mm 
Sum of Diameters 
mm 
mm 
mm 
mm 
mm 
mm 
% Change (% ∆)  from Baseline or Nadir* & absolute value 
(AbV) 
 
NA 
        
          NA 
% ∆ 
                        
        AbV 
 
 
 
 
Target Lesion Response 
      N/A 
 
 
 
 
 
 
Non-Target Lesions 
NON-TARGET Lesions 
Lesion 
Site 
Imaging 
Baseline 
Cycle_____ 
Cycle_____ 
Cycle_____ 
Cycle_____ 
Cycle_____ 
01 
 
 
 
 
 
 
 
 
 
02 
 
 
 
 
 
 
 
 
 
03 
 
 
 
 
 
 
 
 
 
04 
 
 
 
 
 
 
 
 
 
05 
 
 
 
 
 
 
 
 
 
Non-Target Lesion Response 
N/A 
 
 
 
 
 
 
New Lesions 
New 
1 
 
 
 
 
N/A 
 
 
 
 
 
2 
 
 
 
 
N/A 
 
 
 
 
 
3 
 
 
 
 
N/A 
 
 
 
 
 
Overall Tumor Response 
 
 
 
 
Cycle___ 
 
Cycle___ 
 
Cycle___ 
 
 
Cycle___ 
 
 
Cycle___ 
     
 
 
 
 
 
Radiologist Signature: 
 
 
 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 40 of 52 
 
Treating Physician Signature: 
 
 
 
 
 
 
PI Signature: 
 
 
 
 
 
 
 
*Terms & Calculations 
 
 
 
 
 
 
 
Baseline: The set of data collected prior to randomization 
 Nadir: The lowest point   
 
 LIST ALL TARGET AND NON-TARGET SITES TO BE USED FOR RESPONSE: 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 41 of 52 
 
Appendix G – 30 - day Treatment Follow-up Form 
 
Study Number: CCCWFU 62418 
 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Thomas Lycan, DO     Date(mm/dd/yy): ___ ___/___ ___/___ ___ 
 
 
Instructions: Complete this form to follow-up with patients for adverse events. 
Name of Person Competing form_____________________________ 
Did the subject have any adverse events in the last 30 days? 
Yes 
No 
If yes, please describe nature and grade of AE (Note*: If an SAE occurs in this period, report the 
event as required in Appendix D of this protocol): 
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________ 
Was the subject removed from the study by the PI? 
Yes 
No 
Did the subject withdraw from the study? 
Yes 
No 
Did the subject complete the study? 
Yes 
No 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 42 of 52 
 
Appendix H - Adverse Events Log 
 
 
 
 
 
 
 
 
PID #: ___________________________   
MRN #: __________________________________   
CYCLE #: _____________________________   
Adverse Event CTC Term (Version 5.0)  
Lab 
Value 
Grade      
(1-5) per 
CTC 
Start/ End Date 
Attribution  
DEF=Definite 
PROB=Probable 
POSS=Possible 
UNLK=Unlikely 
UNRL=Unrelated 
Action Taken  
NO=None            
 DR=Dose Reduced 
RI=Regimen Interrupted          
TD=Therapy discontinued 
INTR=Interrupted then reduced 
Therapy Given    
NO=None   
SYM=Symptomatic   
SUP=Supportive     
VSUP=Vigorous supportive 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 43 of 52 
 
Appendix I - Survival Data 
 
Study Number: CCCWFU 62418 
 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Thomas Lycan, DO     Date(mm/dd/yy): ___ ___/___ ___/___ ___ 
 
 
Study Visit: 
 End of Cycle 4 ( 8 weeks) 
 2 months post-treatment 
 4 months post-treatment 
 6 months post-treatment 
 8 months post-treatment 
 10 months post-treatment 
 12 months post-treatment 
 14 months post-treatment 
 16 months post-treatment 
 18 months post-treatment 
 20 months post-treatment 
 22 months post-treatment 
 24 months post-treatment  
 26 months post-treatment 
 28 months post-treatment 
 30 months post-treatment 
 32 months post-treatment  
 34 months post-treatment 
 36 months post-treatment 
 38 months post-treatment 
 40 months post-treatment 
 42 months post-treatment 
 44 months post-treatment  
 46 months post-treatment 
 48 months post-treatment 
 Other visit: (please specify) ________________ 
 
 
DATE OF LAST CONTACT (mm/dd/yy): ___ ___ / ___ ___ / ____ ___ 
 
DECEASED:  Y____ N____ Unknown ____ 
 
DATE OF DEATH (mm/dd/yy): ___ ___ / ___ ___ / ____ ___ 
 
 
 
 
 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 44 of 52 
 
Appendix J – Treatment Response Evaluation Form 
 
 
Study Number: CCCWFU 62418 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator Thomas Lycan, DO.     Date (mm/dd/yy): __ __/__ __/__ __ 
 
 
Study Visit: 
 
 After Treatment (Visit 5) 
 Other visit: (please specify) ________________ 
 
Date of Scan (mm/dd/yyyy): ___ ___ /___ ___ /___ ___ ___ ___ 
 
Imaging Modality: 
 CT 
 PET/CT 
 MRI  
 Other____________  
 
Evaluation of Target Lesions 
 
   Complete Response (CR) 
 
   Partial Response (PR) 
 
   Progressive Disease (PD)  
 
   Stable Disease (SD) 
 
   NE  
 
Evaluation of Non-Target Lesions 
 
   Complete Response (CR) 
 
   Non-CR/Non-PD 
 
   Progressive Disease (PD)  
 
   NE  
 
Overall Response this Visit 
   Complete Response (CR) 
   Partial Response (PR) 
 
   Progressive Disease (PD):  Date of progression (mm/dd/yyyy) ___ ___ /___ ___ /___ ___ ___ ___ 
 
   Stable Disease 
 
   NE  
 
Treating Physician Signature: ______________________ 
 
Date (mm/dd/yyyy): ___ ___ /___ ___ /___ ___ ___ ___ 
 
PI Signature: ___________________________________ 
 
Date (mm/dd/yyyy): ___ ___ /___ ___ /___ ___ ___ ___ 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 45 of 52 
 
Appendix K-Evaluation of Best Overall Response 
 
 
 
Study Number: CCCWFU 62418 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator Thomas Lycan, DO     
Date (mm/dd/yy): __ __/__ __/__ __ 
 
 
Study visit of best response: 
 
 After Treatment (Visit 5) 
 Other visit: (please specify) ________________ 
 
Date of scan for best response (mm/dd/yy): ___ ___ /___ ___ /___ ___ 
 
Best Response: 
 
 
Target Lesion 
 
Non-Target Lesion  
 
New Lesions 
 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
NE 
No 
PR 
PR 
Non-PD or not all 
evaluated 
No 
PR 
SD 
Non-PD or not all 
evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
 
Please check one based on clinical review of imaging: 
 
   Complete Response (CR) 
   Partial Response (PR) 
   Progressive Disease (PD) Date of progression (mm/dd/yy): ___ ___ /___ ___ /___ ___ 
   Stable Disease (SD) 
   NE 
 
Please check if patient removed from study due to clinical deterioration for any reason:  
   Symptomatic deterioration 
 
Please explain: _______________________________________________________________  
 
 
 
Treating Physician Signature: ___________________________  
 
Date(mm/dd/yy): ___ ___ /___ ___ /___ ___ 
 
PI Signature: ________________________________________   
 
Date(mm/dd/yy): ___ ___ /___ ___ /___ ___ 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 46 of 52 
 
Appendix L – Off-Study Form  
 
Study Number: CCCWFU 62418 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Thomas Lycan, DO    
Date (mm/dd/yy): __ __/__ __/__ __ 
 
 
Instructions: Complete this form if the patient either withdraws consent or is removed from the 
study.  
 
Name of Person Competing form_____________________________ 
 
Did the subject meet eligibility criteria for study enrollment?   Yes 
   No 
 
 
Was the subject removed from the study per physician decision?  Yes 
   No 
  
(if yes, move to #6) 
 
Did the patient withdraw consent to participate in the study?  Yes 
   No 
  
(if yes move to #1) 
 
Reason for patient withdrawal: 
1. 
 Unacceptable toxicity from Gemcitabine 
2. 
 Unacceptable toxicity from Nivolumab 
3. 
 Did not want to participate anymore. Reason: 
____________________________________________________________________ 
4. 
Other: ____________________________________ 
5. Please specify what portion of the study the subject wishes to withdraw from: 
 
 
 
 For just the (circle) Gemcitabine and/or Nivolumab administration only 
 For all components of the research study (including follow up in the medical 
record)  
 
Reason(s) for Removal:  
6. 
 Patient exhibited progression of disease 
 
7. 
 Unacceptable toxicity from: 
a. 
 Gemcitabine 
b. 
 Nivolumab 
 
8. 
 Investigator’s discretion to withdraw patient from the study because continued 
participation in the study is not in the patient’s best interest (*Describe below) 
 
9. 
 Undercurrent illness: a condition, injury, or disease unrelated to the intended disease 
for which the study is investigating, that renders continuing the treatment unsafe or 
regular follow-up impossible (*Describe below) 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 47 of 52 
 
10. 
 General or specific changes in the patient’s condition that renders the patient 
ineligible for further investigational treatment (*Describe below) 
 
11. 
 Non-compliance with investigational treatment, protocol-required evaluations or 
follow-up visits (*Describe below) 
 
12. 
 Termination of the clinical trial by the clinical sponsor 
 
Comment: 
 
If reason for withdrawal includes options 8-11 then please add comments clarifying this 
information)___________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
___________________________________________________________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 48 of 52 
 
Appendix M – Exploratory Studies Form 
 
Instructions: Use this form to record data related to the exploratory objectives 
 
Study Number: CCCWFU 62418 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Thomas Lycan, DO    
Date (mm/dd/yy): __ __/__ __/__ __ 
 
 
1. Blood Studies 
Visit 
 Baseline 
 Post-Treatment 
 Follow-up (8-12 weeks after treatment) 
 
CD4+ T cells: _________________ 
 
CD8+ T cells: _________________ 
 
2. Tumor mutation burden classification (record when results are available) 
 
 Low (0 to <143 mutations) 
 
 Medium (143 to 247 mutations) 
 
 High (>248 mutations) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 49 of 52 
 
Appendix N – PRO CTCAE & Selected FACIT Items  
NCI PRO-CTCAE™ ITEMS 
Item Library Version 1.0 
English 
Form created on 12 December 2018 
 
This survey is OPTIONAL for study participants. It is designed to assess the patient 
perspective of symptomatic adverse events, treatment tolerability, and health-related 
quality of life using self-reported items. 
 
[  ] Please check here if the questionnaire was offered and the patient DECLINED. 
 
As individuals go through treatment for their cancer they sometimes experience 
different symptoms and side effects. For each question, please check or mark an 
in the one box that best describes your experiences over the past 7 days… 
 
1. In the last 7 days, what was the SEVERITY of your DECREASED APPETITE at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
In the last 7 days, how much did DECREASED APPETITE INTERFERE with your usual 
or daily activities? 
○ Not at all ○ A little bit ○ Somewhat ○ Quite a bit ○ Very much 
 
2. In the last 7 days, how OFTEN did you have NAUSEA? 
○ Never ○ Rarely ○ Occasionally ○ Frequently ○ Almost constantly 
 
In the last 7 days, what was the SEVERITY of your NAUSEA at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
3. In the last 7 days, how OFTEN did you have VOMITING? 
○ Never ○ Rarely ○ Occasionally ○ Frequently ○ Almost constantly 
 
In the last 7 days, what was the SEVERITY of your VOMITING at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
4. In the last 7 days, what was the SEVERITY of your CONSTIPATION at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
5. In the last 7 days, how OFTEN did you have LOOSE OR WATERY STOOLS 
(DIARRHEA/DIARRHOEA)? 
○ Never ○ Rarely ○ Occasionally ○ Frequently ○ Almost constantly 
 
6. In the last 7 days, how OFTEN did you have PAIN IN THE ABDOMEN (BELLY AREA)? 
○ Never ○ Rarely ○ Occasionally ○ Frequently ○ Almost constantly 
 
In the last 7 days, what was the SEVERITY of your PAIN IN THE ABDOMEN (BELLY 
AREA) at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 50 of 52 
 
In the last 7 days, how much did PAIN IN THE ABDOMEN (BELLY AREA) INTERFERE 
with your usual or daily activities? 
○ Not at all ○ A little bit ○ Somewhat ○ Quite a bit ○ Very much 
 
7. In the last 7 days, what was the SEVERITY of your SHORTNESS OF BREATH at its 
WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
In the last 7 days, how much did your SHORTNESS OF BREATH INTERFERE with your 
usual or daily activities? 
○ Not at all ○ A little bit ○ Somewhat ○ Quite a bit ○ Very much 
 
8. In the last 7 days, what was the SEVERITY of your COUGH at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
In the last 7 days, how much did COUGH INTERFERE with your usual or daily 
activities? 
○ Not at all ○ A little bit ○ Somewhat ○ Quite a bit ○ Very much 
 
9. In the last 7 days, what was the SEVERITY of your WHEEZING (WHISTLING NOISE IN THE 
CHEST WITH BREATHING) at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
10. In the last 7 days, did you have any RASH? 
○ Yes ○ No 
 
11. In the last 7 days, what was the SEVERITY of your DRY SKIN at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
12. In the last 7 days, what was the SEVERITY of your ITCHY SKIN at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
13. In the last 7 days, how OFTEN did you have PAIN? 
○ Never ○ Rarely ○ Occasionally ○ Frequently ○ Almost constantly 
 
In the last 7 days, what was the SEVERITY of your PAIN at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
In the last 7 days, how much did PAIN INTERFERE with your usual or daily activities? 
○ Not at all ○ A little bit ○ Somewhat ○ Quite a bit ○ Very much 
 
14. In the last 7 days, how OFTEN did you have a HEADACHE? 
○ Never ○ Rarely ○ Occasionally ○ Frequently ○ Almost constantly 
 
In the last 7 days, what was the SEVERITY of your HEADACHE at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
In the last 7 days, how much did your HEADACHE INTERFERE with your usual or daily 
activities? 
○ Not at all ○ A little bit ○ Somewhat ○ Quite a bit ○ Very much 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 51 of 52 
 
15. In the last 7 days, how OFTEN did you have ACHING MUSCLES? 
○ Never ○ Rarely ○ Occasionally ○ Frequently ○ Almost constantly 
 
In the last 7 days, what was the SEVERITY of your ACHING MUSCLES at their 
WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
In the last 7 days, how much did ACHING MUSCLES INTERFERE with your usual or 
dailyactivities? 
○ Not at all ○ A little bit ○ Somewhat ○ Quite a bit ○ Very much 
 
16. In the last 7 days, how OFTEN did you have ACHING JOINTS (SUCH AS ELBOWS, 
KNEES, SHOULDERS)? 
○ Never ○ Rarely ○ Occasionally ○ Frequently ○ Almost constantly 
 
In the last 7 days, what was the SEVERITY of your ACHING JOINTS (SUCH AS 
ELBOWS, KNEES, SHOULDERS) at their WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
In the last 7 days, how much did ACHING JOINTS (SUCH AS ELBOWS, KNEES, 
SHOULDERS) INTERFERE with your usual or daily activities? 
○ Not at all ○ A little bit ○ Somewhat ○ Quite a bit ○ Very much 
 
17. In the last 7 days, what was the SEVERITY of your INSOMNIA (INCLUDING DIFFICULTY 
FALLING ASLEEP, STAYING ASLEEP, OR WAKING UP EARLY) at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
In the last 7 days, how much did INSOMNIA (INCLUDING DIFFICULTY FALLING 
ASLEEP, STAYING ASLEEP, OR WAKING UP EARLY) INTERFERE with your usual or 
daily activities? 
○ Not at all ○ A little bit ○ Somewhat ○ Quite a bit ○ Very much 
 
18. In the last 7 days, what was the SEVERITY of your FATIGUE, TIREDNESS, OR LACK OF 
ENERGY at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
In the last 7 days, how much did FATIGUE, TIREDNESS, OR LACK OF ENERGY 
INTERFERE with your usual or daily activities? 
○ Not at all ○ A little bit ○ Somewhat ○ Quite a bit ○ Very much 
 
19. In the last 7 days, how OFTEN did you have UNEXPECTED OR EXCESSIVE SWEATING 
DURING THE DAY OR NIGHTTIME (NOT RELATED TO HOT FLASHES/FLUSHES)? 
○ Never ○ Rarely ○ Occasionally ○ Frequently ○ Almost constantly 
 
In the last 7 days, what was the SEVERITY of your UNEXPECTED OR EXCESSIVE 
SWEATING DURING THE DAY OR NIGHTTIME (NOT RELATED TO HOT 
FLASHES/FLUSHES) at its WORST? 
○ None ○ Mild ○ Moderate ○ Severe ○ Very severe 
 
 
 
 


Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU # 62418 
 
  
Protocol version date 05/20/20 
 
 
 
 
 
Page 52 of 52 
 
FACIT Items 
 
Below is a list of statements that other people with your illness have said are important. Please 
circle or mark one number per line to indicate your response as it applies to the past 7 
days.  
 
8. I am bothered by the side effects of treatment.  
 
○ Not at all  
○ A little bit  
○ Somewhat   
○ Quite a bit  ○ Very much 
 
 
9. I am able to do my usual activities.  
 
○ Not at all  
○ A little bit  
○ Somewhat   
○ Quite a bit  ○ Very much 
 
10. I am able to enjoy life.  
 
○ Not at all  
○ A little bit  
○ Somewhat   
○ Quite a bit  ○ Very much 
 
 

ICF_001.pdf: 
Comprehensive Cancer Center 
CCCWFU 62418 
WFU School of Medicine  
 
Version: 06/10/20                                                  Page 1 of 17 
Institutional Review Board  
IRB Number: IRB00051024 
Meeting Date Approved 6/2/2020          
Version Valid Until: 4/8/2021 
Section of Hematology and Oncology 
PHASE II PILOT STUDY OF SUBSEQUENT LINE GEMCITABINE AND  
NIVOLUMAB FOR ADVANCED SMALL CELL LUNG CANCER  
Informed Consent Form to Participate in Research 
Thomas Lycan, DO, Principal Investigator 
SUMMARY 
You are invited to participate in a research study. The purpose of this research is to find 
additional combinations of chemotherapy that may be effective for patients who have incurable 
small cell lung cancer that has gotten worse after being treated with platinum chemotherapy 
(including either cisplatin or carboplatin).  You are invited to be in this study because you have 
incurable small cell lung cancer. Your participation in this research will involve 7 visits 
(possibly more if your doctor feels it is needed) and last about 20 weeks unless your disease 
progresses. You will then be contacted every 8 weeks for the rest of your life to determine your 
progress. 
Participation in this study will involve you receiving a new drug combination to treat your 
cancer. The treatment will include nivolumab and gemcitabine together. You will receive this 
combination for 8 weeks. During this time and after, you will be assessed for progression and 
provide blood samples for research.  All research studies involve some risks.  A risk to this study 
that you should be aware of is fatigue, shortness of breath, diarrhea, or autoimmune problems. 
There is the possibility that you may 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 
taking nivolumab alone, other chemotherapy, or no treatment.  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 Thomas Lycan.  
If you have any questions, suggestions or concerns about your rights as a volunteer in this 
research, contact the Institutional Review Board or the Research Subject Advocate at Wake 
Forest 
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 incurable lung cancer. 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 


Comprehensive Cancer Center 
CCCWFU 62418 
WFU School of Medicine  
 
Version: 06/10/20                                                  Page 2 of 17 
Institutional Review Board  
IRB Number: IRB00051024 
Meeting Date Approved 6/2/2020          
Version Valid Until: 4/8/2021 
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 study is to find additional combinations of chemotherapy that may 
be effective for patients who have small cell lung cancer that has gotten worse after being treated 
with platinum chemotherapy (including either cisplatin or carboplatin).  
Nivolumab is an immune checkpoint inhibitor (immunotherapy) that has been approved by the 
Food and Drug Administration (FDA) for other types of lung cancer including small cell lung 
cancer but not in combination with gemcitabine.  
Gemcitabine is a lung cancer chemotherapy drug that also has been approved by the Food and 
Drug Administration (FDA) for other types of lung cancer but not for small cell lung cancer and 
not in combination with nivolumab.  
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
There will be approximately 29 people at one research site that will take part in this study. 
WHAT IS INVOLVED IN THE STUDY? 
You will have been identified in the clinic as a potential candidate for this study. Once you sign 
this informed consent you will fulfill the needed pre-study requirements, some of which may 
already have been collected through your standard care. 
Pre-Study Requirements 
Before the study begins we will ensure you are eligible for the study by collecting your medical 
information. This information will include demographics, medical history, current medication 
use, vital signs, your height and weight, and your performance status (a measure of how your 
cancer is affecting you). You will also give blood so that we can examine the make-up of your 
blood to make sure your organs are functioning and/or to make sure your blood readings are 
within certain limits. If you are a woman of childbearing potential and you have not taken a 
recent pregnancy test, you will be asked to have a pregnancy test. We will also take tumor 
measurements from pictures of of your tumor(s). Finally, we will ask for an extra blood sample 
of about 8 teaspoons that will be used for research.  
Treatment Phase 
You will be started on treatment with both nivolumab and gemcitabine. You will receive these 
drugs in cycles. A cycle of drug administration is a period of time when you take the drug and 
then let your body recover. You will give 1-5 teaspoons of blood at the beginning of each cycle 
and this is a part of your standard care so that we can examine the make-up of your blood to 
make sure your organs are functioning and/or to make sure your blood readings are within 
certain limits. This means you would give this blood even if you were not on the study. The 
cycles of drug are described below. In this study the cycles will last 2 weeks each and you will 
be treated for 4 cycles for a total of 8 weeks. 


Comprehensive Cancer Center 
CCCWFU 62418 
WFU School of Medicine  
 
Version: 06/10/20                                                  Page 3 of 17 
Institutional Review Board  
IRB Number: IRB00051024 
Meeting Date Approved 6/2/2020          
Version Valid Until: 4/8/2021 
You will have 4 cycles of both nivolumab and gemcitabine and all 4 cycles will be like 
the process described below for cycle 1: Cycle 1 Day 1. 
• 
You will give blood for routine clinical testing 
• 
You will receive nivolumab and gemcitabine through a vein 
Days 2-14 
• 
You will not receive any drug 
You will repeat this for the next 3 cycles  
Your physician may recommend you continue chemotherapy after the 4 cycles have been 
completed depending upon how your disease is responding. 
After Chemotherapy Phase 
Once you have taken all 4 cycles of chemotherapy, your tumor will be measured by either CT or 
MRI imaging. You will also have a physical exam and your vital signs will be recorded. This 
will all be a part of your standard care. You will also give 8 teaspoons of blood for research 
purposes. 
Follow-up Phase 
The follow-up phase will take place after chemotherapy. We will follow you for 30 days after 
you take your last study drug. At or around 6-10 weeks after your last study drug administration 
you will come back in for a physical exam, vital signs, tumor imaging, and you will give blood 
for clinical blood work. This is all part of your standard care. You will also give 8 teaspoons of 
blood for research purposes. 
IF YOU TAKE PART IN THIS STUDY, YOU WILL HAVE THE FOLLOWING TESTS AND PROCEDURES: 
Blood Draws 
You will have approximately 8 teaspoons of blood withdrawn from a vein 9 times; before study 
treatment starts, at the beginning of each treatment cycle, at the end of treatment, and then in a 
follow-up period sometime after treatment. These 6 draws will be a part of your standard care. 
At 3 of these blood draws (before the study treatment starts, at the end of treatment and in 
follow-up after treatment) you will have 8 extra teaspoons of blood collected to test for research 
purposes. The total amount of blood withdrawn during the study will be approximately 18-54 
teaspoons from 9 draws over the length of the study.  
Imaging of your Tumor(s) 
You will have your tumors measured. To do this we will need to take pictures of your tumors by 
one of two methods. Your doctor will decide which type of imaging is best in your situation. 
You may have Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). You will 
have this done at the beginning of the study and after treatment is completed (8 weeks after 
treatment starts). This imaging is a part of your standard care and would be done even if you 
were not in the study. 


Comprehensive Cancer Center 
CCCWFU 62418 
WFU School of Medicine  
 
Version: 06/10/20                                                  Page 4 of 17 
Institutional Review Board  
IRB Number: IRB00051024 
Meeting Date Approved 6/2/2020          
Version Valid Until: 4/8/2021 
We can send copies of your test results to your personal physician. Even if you do not wish to 
have any of your medical information sent to your physician, you can still participate in this 
research study.  The types of tests that may be made available are routine blood tests, your 
response to therapy, type of therapy, and other information related to your care. 
Do you request that we send important medical findings from your study tests/exams to your 
personal physician?  
 
[   ] Yes 
[   ] No 
___________ Initials 
Your information or biospecimen that will be collected as part of this research study, even if 
identifiers are removed, will not be used or distributed for future research. 
Storage of Biological Tissue 
If you agree to participate in this study, we will draw blood up to 8 teaspoons of blood 3 times to use this 
research project and the remainder will be stored for future research. This research includes analysis of 
your blood samples for immune cell function.  This sample will be kept and may be used in future research 
to learn more about other diseases.  Your sample will be obtained and then initially stored in the 
Comprehensive Cancer Center at Wake Forest University Baptist Medical Center. The sample will then be 
transferred for storage and analysis by researchers approved by Dr. Thomas Lycan.  An Institutional Review 
Board (IRB) must also approve any future research study using your blood sample. In order to participate 
in this study, you must be willing to provide this sample for future research.  
Your blood sample will be stored with a unique identifier and will not include any identifiable 
information about you such as your name, address, telephone number, social security number, 
medical record number or any of the identifiers outlined in the HIPAA Privacy Rule. The unique 
identifier will be a randomly assigned number and only the principal investigator will have 
access to the code that links the unique identifier to you. Your name, address, social security 
number, etc., will never be disclosed to future researchers and neither will the code that links 
your identifiers to the sample. 
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. 
It is unknown as to what the blood will be used for in future research but may include tests that 
look at your and your tumor’s DNA make-up, or the components (cell and molecules) that are in 
your blood. Your blood may be used for research not related to your disease. Your blood may be 
used in some animal research.  
HOW LONG WILL I BE IN THE STUDY? 
You will be in the study for about 20 weeks unless your disease progresses. We will then follow 
your progress by reviewing your chart, every 8 weeks for the rest of your life. 


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You can stop participating at any time. 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. This may include progression of cancer and/or late complications of cancer 
treatment which can go unrecognized without monitoring.  


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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. Risks and side effects related to the drugs we are studying include: 
Risks of Nivolumab  
In general, nivolumab has a risk (>10%) of developing autoimmune complication(s), such as 
inflammation of the thyroid (hypothyroidism or hyperthyroidism), colon (colitis), lungs 
(pneumonitis), liver (hepatitis), or pituitary gland (hypophysitis), which can lead to the 
symptoms noted below. Autoimmune complications can potentially be life-threatening or 
permanent. In some cases they may be reversible with urgent administration of steroids and 
other immunosuppressant(s).  
More common (>10% of patients): 
• 
back painchest tightness 
• 
chills 
• 
constipation 
• 
cough 
• 
depressed mood 
• 
diarrhea 
• 
dry skin and hair 
• 
feeling cold 
• 
fever 
• 
flushing 
• 
hair loss 
• 
headache 
• 
hoarseness or husky voice 
• 
itching 
• 
joint or muscle pain 
• 
muscle cramps and stiffness 
• 
nausea and vomiting 
• 
red, irritated eyes 
• 
slowed heartbeat 
• 
skin rash 
• 
sore throat 
• 
sores, ulcers, or white spots in the mouth or on the lips 
• 
trouble breathing 
• 
unusual tiredness or weakness 


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• 
weight gain 
• 
stuffy or runny nose Less common (<10% of patients): 
• 
chest pain dark urine general feeling of discomfort or illness light-colored stools 
nervousness pain 
sensitivity to heat stomach cramps 
sweating swelling of the face, feet, or 
lower legs tenderness 
• 
thickening of bronchial secretions 
• 
trouble sleeping 
• 
upper right abdominal or stomach pain 
• 
watery or bloody diarrhea 
• 
weight loss 
• 
yellow eyes and skin 
Rare (<1% of patients) 
• 
bloating 
• 
bloody or cloudy urine 
• 
blurred vision or other change in vision 
• 
darkening of the skin 
• 
dizziness 
• 
drowsiness 
• 
eye pain 
• 
fainting 
• 
fast heartbeat 
• 
indigestion 
• 
loss of appetite 
• 
mental depression 
• 
pains in the stomach, side, or abdomen, possibly radiating to the back 
• 
redness of the eye 
• 
sensitivity of the eye to lightskin blistering, peeling, or looseningtearing 
Risks for Gemcitabine 


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Major Side Effects 
You should check with your doctor immediately if any of these side effects occur when 
taking gemcitabine: 
More common (>10% of patients): 
 Bleeding gums 
• 
blood in urine or stools 
• 
burning, crawling, itching, numbness, prickling, "pins and needles", or tingling 
feelings 
• 
chest pain 
• 
cloudy urine 
• 
coughing up blood cough or hoarseness diarrhea difficult or labored breathing 
difficulty in moving difficulty in swallowing dizziness fever or chills general feeling 
of discomfort or illness headache 
increased menstrual flow or vaginal bleeding 
• 
joint pain 
• 
lack or loss of strength 
• 
loss of appetite 
• 
lower back or side pain 
• 
muscle aching or cramping 
• 
muscle pains or stiffness 
• 
nausea 
• 
nosebleeds 
• 
painful or difficult urination 
• 
pale skin  paralysis 
• 
pinpoint red spots on skin 
• 
prolonged bleeding from cuts 
• 
red or black, tarry stools 
• 
red or dark brown urine 
• 
runny nose 
• 
shivering 
• 
shortness of breath 


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• 
sores, ulcers, or white spots on lips or in mouth 
• 
sore throat 
• 
sweating 
• 
swelling of hands, ankles, feet, or lower legs 
• 
swollen glands 
• 
swollen joints 
• 
tightness in chest 
• 
troubled breathing with exertion 
• 
trouble sleeping 
• 
unusual bleeding or bruising 
• 
unusual tiredness or weakness 
• 
vomiting 
• 
weight loss 
• 
wheezing 
Less common (<10% of patients): 
 Blurred vision 
• 
chest discomfort fainting fast, slow, or irregular heartbeat headache (sudden and 
severe) inability to speak nervousness 


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noisy breathing pain or discomfort in arms, 
jaw, back or neck pounding in the ears 
seizures 
slurred speech 
• 
temporary blindness 
• 
weakness in arm and/or leg on one side of the body (sudden and severe) Rare (<1% 
of patients)  Confusion 
• 
lightheadedness 
• 
rapid, shallow breathing 
Incidence not determined (these have been observed but it is unclear as to how common they 
are) 
• 
Hives 
• 
itching 
• 
puffiness or swelling of the eyelids or around the eyes, face, lips or tongue  skin rash 
Some of the side effects that can occur with gemcitabine may not need medical attention. As 
your body adjusts to the medicine during treatment these side effects may go away. Your health 
care professional may also be able to tell you about ways to reduce or prevent some of these side 
effects. If any of the following side effects continue, are bothersome or if you have any questions 
about them, check with your health care professional: 
More common: 
• 
Difficulty having a bowel movement (stool) 
• 
hair loss 
• 
pain 
• 
sleepiness or unusual drowsiness 
• 
swelling or inflammation of the mouth 
• 
thinning of hair Less common: 
• 
Bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, 
hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, 
scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at 
site 
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 CT and MRI 


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The MRI and CT scans are a part of your standard care and will be explained by your physician.  
Risks of Providing Confidential or Private Information 
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. 
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 unknown 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. Birth control should be continued for at least one month after 
completion of study date. If further cancer treatments are planned then birth control should be 
continued as directed by the treating physician. 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. Because some methods of birth 
control are not 100% reliable, a pregnancy test is required at least 10 days from your last normal 
menstrual period, if you are a sexually active woman of childbearing potential. 
Contraceptive Measures for Males 
Your participation in this research study may damage your sperm, which could cause harm to a 
child that you may father while on this study. Such harm may be currently unforeseeable. If you 
are sexually active, you must agree to use a medically acceptable form of birth control in order to 
be in this study and for 12 months afterwards. Medically acceptable contraceptives include: (1) 
surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicide.  
Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are 
not acceptable methods for routine use. You should inform your partner of the potential for harm 
to an unborn child. She should know that if pregnancy occurs, you will need to report it to the 
study doctor, and she should also promptly notify her doctor. 
ARE THERE BENEFITS TO TAKING PART IN THE STUDY? 
If you agree to take part in this study, there may or may not be direct benefit to you. We hope the 
information learned from this study will benefit other people in the future.  


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Based on experience with clinical research studies in humans, researchers believe that the 
addition of low-dose chemotherapy may be able to generate a response to nivolumab in patients 
who have not already responded. Such a response may be able to prolong the amount of time 
until your cancer progresses. Because individuals respond differently to therapy, no one can 
know in advance if it will be helpful in your particular case. 
WHAT OTHER CHOICES ARE THERE? 
You do not have to be in this study to receive treatment. You should talk to your doctor about all 
the choices you have. Instead of being in this study, you have the option to continue with the 
usual care given to patients who have advanced small cell lung cancer.  There are currently no 
other research studies available at this site for your disease type.   
The usual care of these patients often includes several options: 
1) Treatment with an immune checkpoint inhibitor (such as nivolumab). The benefit is that there 
may be a response with immunotherapy alone, but the risk is that the treatment will be 
ineffective and the disease continues to progress or that the treatment will have side effects. 2) 
Treatment with chemotherapy. The benefit is that there may be a response with chemotherapy 
alone, but the risk is that the treatment will be ineffective and the disease continues to progress 
or that the treatment will have side effects. 
3) Stopping treatment. The benefit is that there will not be treatment toxicity without any 
treatment, the risk is that the cancer will continue to progress without treatment. 
WHAT ARE THE COSTS? 
Taking part in this study may lead to added costs to you or your insurance company. We will 
give you an estimate of what the added cost may be based on your particular situation and 
insurance coverage. 
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 either gemcitabine when used with nivolumab; the results will be provided to the 
sponsor, the Food and Drug Administration and other federal and regulatory agencies as 
required. 


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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 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 
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 or other compensation for taking part in this study. However, 
parking will be paid for any study related visits. 
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 


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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. 
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 Thomas Lycan, DO. 
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:  
demographic information, laboratory test results, medical history, your response to treatments 
and medications you are or have taken. 
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 will 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.   


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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 an indeterminate period of time. This authorization does not 
expire. 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 
completely finished.  
You can tell Thomas Lycan, DO  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: 
Thomas Lycan, DO 
Medical Center Blvd 
Winston-Salem, NC 27157 
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 


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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 
at any time. This could be because your condition gets worse, the principal investigator 
determines this study is not in your best medical interest, or the study closes.   
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. 
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 or the Research Subject 
Advocate. 
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 


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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