A Pilot Study of MUC1 Vaccine in Current and Former Smokers at High Risk for Lung Cancer
Phase: PHASE1
Conditions: Lung Carcinoma
Sponsor: National Cancer Institute (NCI)

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DCP Protocol #:  MAY2016-08-01  
 
Local Protocol #:  MAY2016-08-01  
 
A Pilot Study of MUC1 Vaccine in Current and Former Smokers at High Risk for Lung Cancer 
 
Consortium Name: 
 
 
Cancer Prevention Network (CPN)  
Name of Consortium Principal   
Paul J. Limburg, M.D., M.P.H.  
Investigator: 
 
 
Mayo Clinic 
 
200 First Street, SW, Rochester, MN  55905 
 
Telephone:  507-284-2511 
 
Fax:  507-266-4371 
 
E-mail:  limburg.paul@mayo.edu 
 
Organization:  
 
 
National Cancer Institute, Division of Cancer Prevention 
Protocol Scientific and Medical        Malgorzata (Margaret) Wojtowicz, M.D. 
Monitor:                                                 National Institutes of Health, National Cancer Institute,  
                                                                 Division of Cancer Prevention 
                                                                 Lung and Upper Aerodigestive Cancer Research Group 
                                                                 9609 Medical Center Drive, Rm 5E-104, MSC9781 
                                                                 Bethesda, MD 20892 (For FedEx, use Rockville, MD  20850) 
                                                                 Phone:  240-276-7012   
                                                                 Fax:  240-276-7848 
                                                                 Email: wojtowim@mail.nih.gov 
 
Organization:   
 
 
University of Pittsburgh 
Protocol Principal Investigator:        Arjun Pennathur, M.D. FACS * 
 
 
 
 
 
University of Pittsburgh School of Medicine 
 
 
 
 
 
Sampson Family Endowed Chair in Thoracic Surgical Oncology 
 
 
 
 
 
200 Lothrop Street, Suite C-800 
 
 
 
 
 
Pittsburgh, PA  15212 
Telephone:  412-648-6271 
Fax: 412-647-3104 
E-mail:  pennathura@upmc.edu  
 
Organization:   
 
 
University of Pittsburgh 
Co-Principal Investigator: 
       Olivera J. Finn, Ph.D. † 
 
 
 
 
 
University of Pittsburgh School of Medicine 
 
 
 
 
 
Department of Immunology 
 
 
 
 
 
E1040 Biomedical Science Tower 
 
 
 
 
 
Pittsburgh, PA  15262 
Telephone:  412-648-9816 
Fax: 412-648-9378 
 
 
 
 
 
E-mail:  ojfinn@pitt.edu 
 

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Organization:  
 
 
Mayo Clinic 
Co-Investigator 
                  David E. Midthun, M.D. 
 
 
 
                      200 First Street Southwest, Rochester, MN  55905 
                                                                 Phone: 507-284-2511 
                                                                 Fax: 507-266-4371 
                                                                 Email: Midthun.david@mayo.edu 
 
Organization: 
 
 
Mayo Clinic 
Statisticians: 
 
 
Nathan R. Foster, M.S. † and Sumithra J. Mandrekar, Ph.D. † 
 
 
 
200 First Street, SW, Rochester, MN  55905 
 
 
 
Telephone:  507-284-5051; 507-266-6724 
 
 
 
Fax:  507-266-2477 
 
 
 
E-mail:  foster.nathan@mayo.edu; mandrekar.sumithra@mayo.edu 
 
 
 
 
 
 
* Investigator having NCI responsibility for this protocol  
† Study Contributor(s) not responsible for patient care 
 
ClinicalTrials.gov 
NCT03300817 
IND Sponsor: 
 
NCI/Division of Cancer Prevention  
 
 
 
 
IND# 
 
 
#
 
Agent(s)/Supplier: 
MUC1 peptide, U. of Pittsburgh/Poly ICLC adjuvant: Oncovir, Inc.  
Contract # 
 
HHSN261201200042I 
Protocol Version Date:  January 25, 2021 
 
Protocol Revision or  
 
Amendment #  
Version 5.0, Amendment 6 
 
 
 

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SCHEMA 
A Pilot Study of MUC1 Vaccine in Current and Former Smokers at High Risk for Lung Cancer 
 
 
 
 
 
Target Population  
• 
Ages 55-80 years 
• 
Current and former smokers; ≥ 30 pack-year history of smoking 
• 
Chest CT ≤ 6 mo. prior to Registration indicating no evidence of 
cancer; or solid and part-solid nodules < 6mm OR consistent 
with < 1% probability of malignancy, Lung-RADs Version 1.0 
 
Informed consent and Pre-Registration (n=85) 
Screening (n=85) 
• 
Physical exam, med/surgical history, vitals, alcohol and tobacco 
use assessments  
• 
Lung function/spirometry 
• 
Blood tests for eligibility and baseline values 
• 
Urine cotinine test 
• 
Pregnancy test, if applicable 
Registration (n=50) 
• 
Expected screen failure rate:  up to41% 
Intervention (n=50) 
• 
Blood testing for safety/ toxicity at Week 2 (prior to injection), 
Week 4, Week 10 (prior to injection), and Week 12 
• 
Blood testing for immune response at Week 2 (prior to 
injection), Week 4, and Week 12 
• 
Pregnancy test, if applicable 
• 
Urine cotinine test  
• 
MUC1 vaccine at Weeks 0, 2, 10 
• 
Monthly contact for AE and Con Med Assessment 
 
Post-Intervention, Week 24 (or early termination) 
• 
Blood testing for safety and toxicity and immune response 
• 
Urine cotinine test  
• 
Physical exam, lung function/spirometry 
• 
Alcohol and Tobacco Use Follow-up assessments 
• 
Was It Worth It Questionnaire 
• 
Follow up according to standards of good clinical practice 
 

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Endpoints (n=40 evaluable) 
• 
Expected drop-out/non-evaluable rate ~20% 
• 
Primary Endpoints: 
o Immunogenicity response (antibody titer ≥ 2-fold higher at Week 12 compared to baseline) 
o Safety, assessed throughout the trial and continued observation for 24 Weeks  
• 
Secondary Endpoints:  
o Immunogenicity in current vs. former smokers 
o Correlation between Pre- vs. post-vaccination levels of MDSCs and response to vaccine 
Optional Follow-Up (Week 28) 
• 
Optional telephone call to assess AEs/SAEs (and Concomitant 
Medications, if applicable) not resolved at the time of the 
Week 24 visit. 

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TABLE OF CONTENTS  
 
 
SCHEMA .................................................................................................................................. 5 
1. 
OBJECTIVES ................................................................................................................... 10 
1.1 
Primary Objectives .................................................................................................. 10 
1.2 
Secondary Objectives .............................................................................................. 10 
1.3 
Exploratory Objectives ............................................................................................ 10 
2. 
BACKGROUND............................................................................................................... 10 
2.1 
Lung Cancer ............................................................................................................. 10 
2.2 
Study Agent: MUC1/Poly-ICLC Vaccine .................................................................... 11 
2.3 
Rationale ................................................................................................................. 15 
3. 
SUMMARY OF STUDY PLAN .......................................................................................... 16 
4. 
PARTICIPANT SELECTION ............................................................................................... 17 
4.1 
Pre-Registration Inclusion Criteria ........................................................................... 17 
4.2 
Pre-Registration Exclusion Criteria .......................................................................... 18 
4.3 
Registration Inclusion Criteria ................................................................................. 18 
4.4     
Registration Exclusion Criteria ................................................................................. 18 
4.5   
Inclusion of Women and Minorities ........................................................................ 19 
4.6 
Recruitment and Retention Plan ............................................................................. 19 
5. 
AGENT ADMINISTRATION ............................................................................................. 19 
5.1 
Dose Regimen and Dose Groups .............................................................................. 19 
5.2     
MUC1/Poly-ICLC Vaccine Administration ................................................................. 19 
5.3 
Run-in Procedures ................................................................................................... 20 
5.4 
Contraindications .................................................................................................... 20 
5.5 
Concomitant Medications ....................................................................................... 20 
5.6 
Dose Modification ................................................................................................... 20 
5.7 
Adherence/Compliance ........................................................................................... 20 
6. 
PHARMACEUTICAL INFORMATION ................................................................................ 21 
6.1 
MUC1 Vaccine (IND # 
 NCI, Division of Cancer Prevention) ........................... 21 
6.2 
Reported Adverse Events and Potential Risks .......................................................... 22 
6.3  
Availability .............................................................................................................. 24 
6.4 
Agent Distribution ................................................................................................... 25 
6.5  
Agent Accountability ............................................................................................... 25 
6.6 
Packaging and Labeling ........................................................................................... 25 
6.7 
Storage .................................................................................................................... 25 
6.8 
Pre-Registration and Registration ............................................................................ 26 
6.9 
Blinding and Unblinding Methods ........................................................................... 27 
6.10 
Agent Destruction/Disposal .................................................................................... 27 
7. 
CLINICAL EVALUATIONS AND PROCEDURES .................................................................. 28 
7.1 
Schedule of Events .................................................................................................. 28 
7.2 
Baseline Testing/Pre-study Evaluation .................................................................... 30 
7.3 
Evaluation During Study Intervention ...................................................................... 30 

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7.4 
Evaluation at Completion of Study Intervention (or early termination) ................... 31 
7.5 
Post-Intervention Follow-up Period ......................................................................... 31 
7.6 
Methods for Clinical Procedures .............................................................................. 31 
8.  
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION .............................................. 31 
8.1 
Primary Endpoint .................................................................................................... 31 
8.2 
Secondary Endpoints ............................................................................................... 31 
8.3 
Off-Agent Criteria .................................................................................................... 31 
8.4 
Off-Study Criteria .................................................................................................... 31 
8.5 
Study Termination ................................................................................................... 31 
9. 
CORRELATIVE/SPECIAL STUDIES .................................................................................... 32 
9.1 
Rationale for Methodology Selection ...................................................................... 32 
9.2 
Comparable Methods .............................................................................................. 34 
10. SPECIMEN MANAGEMENT ............................................................................................ 34 
10.1 
Laboratories ............................................................................................................ 34 
10.2 
Collection and Handling Procedures ........................................................................ 34 
10.3 
Shipping Instructions ............................................................................................... 36 
10.4 
Biospecimen Banking .............................................................................................. 36 
11. REPORTING ADVERSE EVENTS ....................................................................................... 37 
11.1 
Adverse Events ........................................................................................................ 38 
11.2 
Serious Adverse Events ........................................................................................... 39 
12. STUDY MONITORING .................................................................................................... 41 
12.1 
Data Management .................................................................................................. 41 
12.2 
Case Report Forms .................................................................................................. 41 
12.3 
Source Documents .................................................................................................. 41 
12.4 
Data and Safety Monitoring Plan ............................................................................. 42 
12.5 
Sponsor or FDA Monitoring ..................................................................................... 42 
12.6 
Record Retention .................................................................................................... 42 
12.7 
Cooperative Research and Development Agreement/Clinical Trials Agreement ...... 43 
13. STATISTICAL CONSIDERATIONS ..................................................................................... 43 
13.1 
Study Design/Description ........................................................................................ 43 
13.2 
Randomization/Stratification .................................................................................. 43 
13.3 
Accrual and Feasibility ............................................................................................. 43 
13.4 
Primary Objective, Endpoint(s), Analysis Plan ......................................................... 44 
13.5 
Secondary Objectives, Endpoints, Analysis Plans ..................................................... 45 
13.6 
Reporting and Exclusions ......................................................................................... 45 
13.7 
Evaluation of Toxicity .............................................................................................. 46 
13.8 
Evaluation of Response ........................................................................................... 46 
13.9 
Interim Analysis ...................................................................................................... 47 
13.10 
Ancillary Studies ...................................................................................................... 47 
14. ETHICAL AND REGULATORY CONSIDERATIONS ............................................................. 47 
14.1 
Form FDA 1572 ........................................................................................................ 47 
14.2 
Other Required Documents ..................................................................................... 47 
14.3 
Central Institutional Review Board (CIRB)Approval ................................................. 48 

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14.4 
Informed Consent ................................................................................................... 48 
14.5 
Submission of Regulatory Documents ..................................................................... 48 
14.6 
Other ....................................................................................................................... 49 
15. FINANCING, EXPENSES, AND/OR INSURANCE ............................................................... 49 
 
REFERENCES .......................................................................................................................... 49 
 
Informed Consent Template -  Summary of Changes ............................................................. 53 
NCI, DCP Consent Form Template for Consortia Cancer Chemoprevention Trials................... 54 
APPENDIX A: ECOG Performance Status Scale ....................................................................... 70 
APPENDIX B: Glossary ............................................................................................................ 71 
APPENDIX C: Was It Worth It Questionnaire .......................................................................... 72 
APPENDIX D: Vaccine Report Card ......................................................................................... 73 
APPENDIX E: Alcohol and Tobacco Use Assessments ............................................................. 77 
APPENDIX F: Alcohol and Tobacco Cessation Resources ........................................................ 84
 
 
 

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1. 
OBJECTIVES 
 
1.1 
Primary Objectives   
 
• 
Immunogenicity of the vaccine, assessed at week 12, based on the increase in IgG anti-MUC1 
antibody titer over the pre-vaccination levels 
• 
Safety, assessed throughout the trial and continued observation for 24 weeks 
 
1.2 
Secondary Objectives   
 
• 
To explore potential differences, if any, in the immunogenicity of the vaccine (as assessed at week 
12 by the IgG anti-MUC1 antibody titer ratio) in current vs. former smokers.  
• 
To evaluate pre-vaccination levels of circulating myeloid derived suppressor cells (MDSC) and 
correlate with the ability to respond to the vaccine. 
 
1.3 
Exploratory Objectives 
 
• 
To explore immune response at Week 24 
• 
To explore the relationship between COPD status at pre-registration and immune response in 
current versus former smokers 
• 
To explore the impact of the MUC1/Poly-ICLC vaccine on inflammation-related high sensitivity C-
reactive protein (hsCRP) and interleukin-6 (IL-6) levels  
• 
To explore the impact of baseline levels of hsCRP and IL-6 on the ability to successfully vaccinate 
with MUC1/Poly-ICLC 
• 
To establish a biospecimen repository archive:  frozen peripheral blood live cells and plasma for 
future more detailed and comprehensive immunologic assays, including direct testing of anti-MUC1 
T cell immunity 
 
2. 
BACKGROUND 
 
2.1 
Lung Cancer 
 
Lung cancer is the most common neoplasm in the United States, and in 2017, an estimated 222,500 
people in the United States will be diagnosed with lung cancer.1  It kills more men and women than the 
combined incidence of the next four most common cancers, with an estimated 155,870 (lung and 
bronchus) deaths in 2017 in the United States.1  Worldwide, it is estimated that 1.8 million new lung 
cancers were diagnosed in 2012.2  Tobacco smoking is the most common underlying etiology for lung 
cancer, with an estimated 80-90% of patients having a smoking history.3, 4  Smoking cessation is an 
essential component for prevention of lung cancer. However, this strategy has limitations.  Smoking 
cessation is challenging, and even when smoking cessation is successful, it does not immediately 
eliminate the risk of lung cancer, although the risks decrease over time.5, 6  Notably, more than 50% of 
lung cancers occur in individuals who have quit smoking.7  This risk of lung cancer remains higher 
compared to never smokers even 40 years after quitting smoking.3   
 
Survival is poor after diagnosis of lung cancer (15% 5-year survival), and new strategies for prevention of 
this deadly disease are urgently needed, such as chemoprevention.  However, to date, chemopreventive 

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and cellular responses have been reported.  At the University of Pittsburgh Cancer Center, we have run 
seven clinical trials of a therapeutic cancer vaccine using the unglycosylated VNTR 100mer MUC1 
peptide representing 5 tandem repeats, a highly immunogenic form not found on normal epithelial cells, 
combined with various adjuvants.     
 
Trials in resected pancreatic cancer were performed under the condition of minimal residual disease.  In 
the first trial, we used MUC1 100mer peptide plus the SB-A2 adjuvant from SKB.  The vaccine was safe 
and induced low level IgG antibody and low frequency of T cells in several participants.  Two of 16 
participants were alive and disease-free at 32 and 61 months of follow up, and no toxicity was seen that 
could be attributed to the vaccine.20  The second Phase I/II trial used MUC1 100mer-peptide-loaded on 
DC.21 The vaccine was well-tolerated and non-toxic in 12 participants enrolled. The participants were 
followed for over four years, and 4 of the 12 participants were alive without evidence of recurrence at 5 
years.  Elsewhere, a randomized phase IIB trial of Stimuvax MUC1 cancer vaccine, which consists of 
MUC1 25aa peptide from the VNTR formulated in liposomes (BLP25) and given with the 
immunoadjuvant monophosphoryl lipid A, showed efficacy (a median survival of 30.6 months vs. 13.3 
months in controls) in individuals with stage IIIB and IV non-small-cell lung cancer (NSCLC).22  This 
vaccine progressed to Phase III showing a similar therapeutic benefit, in a predefined subgroup treated 
with concurrent chemoradiotherapy, even though the overall study result (combined response in stage 
III and stage IV patients) was negative.23  Therapeutic vaccines using MUC1 engineered into viral vectors 
are being tested primarily at NCI (pox vectors) and at a company called Transgene, in France (vaccinia 
vectors).   
 
In the NCI trial, 25 individuals with various adenocarcinomas were treated with a poxviral vaccine 
regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules. The 
vaccine was well-tolerated.  Low but detectable immune responses to MUC-1 (and/or CEA) were seen in 
9 of 16 participants.24  In the randomized Phase IIb portion of the TIME trial, addition of a MUC1 vaccine 
TG4010 to standard first-line chemotherapy in advanced non-small-cell lung cancer resulted in 
significant improvement in the primary endpoint of progression-free survival and in an increased 
proportion of patients achieving a response. Overall survival was also significantly improved in certain 
subgroups, including non-squamous histology, when compared with the control group of first-line 
chemotherapy and placebo.25, 26  
 
Prophylactic MUC1 vaccines  
Completed feasibility study of the MUC1 vaccine in individuals at high risk for colon cancer:  When this 
study opened at the University of Pittsburgh in 2008,16 it was the first time that a vaccine directed to a 
non-viral tumor antigen was administered to study participants without tumors.  The vaccine was 
composed of the same MUC1 100mer peptide used previously in 7 therapeutic vaccine trials at the 
University of Pittsburgh from 1993 until 2008.  The peptide was admixed with a TLR3 adjuvant, Poly-ICLC 
(Hiltonol), also used previously as adjuvant in some of our therapeutic MUC1 vaccines.  Thirty-nine 
individuals with a previous diagnosis of advanced colon adenoma, a premalignant lesion that could 
progress to colon cancer if not detected on time by colonoscopy and removed, completed the trial.  
Participants were vaccinated at W0, W2 and W10, and their immune response specific for the MUC1 
peptide was evaluated at Week 12 and compared to pre vaccination. A booster shot was administered 
at one year to evaluate MUC1 specific immune memory.  Forty-four percent of participants made anti-
MUC1 IgG in response to the vaccine, at levels much higher than ever seen with the same vaccine in 
cancer patients.   
 

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Most importantly, all tests to evaluate toxicity (evidence of reactivity of the vaccine-induced immune 
response against normal tissues) during the duration of the trial and after more than 150 injections 
administered, indicated only minor adverse events, and these participants have remained without any 
vaccine-related adverse events for over 8 years.  The surprise in this study was that 56% of participants 
did not respond to the vaccine.  We examined the most likely factors such as age, gender and HLA type, 
as possible correlates with response and found no correlations.  However, when we examined the pre-
vaccination PBMC, we saw that the non-responders had statistically significant increases in circulating 
myeloid-derived suppressor cells (MDSC).  MDSCs can strongly suppress development of adaptive 
immunity. 
 
Ongoing placebo-controlled multi-center MUC1 vaccine trial in individuals at high risk for colon cancer:  
Based on the data from the pilot trial (see previous section), we are currently running a larger multi-
center, 1:1 placebo controlled efficacy trial of the same vaccine in participants with recently diagnosed 
advanced adenomas. As of the date of submission for this proposal, ninety-seven of the planned 110 
evaluable participants have been accrued over the last two years.  Most of them have completed the 
first phase of the vaccine, W0-W12, and some have already reached the one-year booster stage. 
Because it is expected that 48% of these individuals will have a polyp recurrence within 1-3 years from 
diagnosis, trial participants will be followed for at least 3 years with polyp recurrences recorded.  We 
expect between 40-50% responders and equal number of vaccine non-responders, due to increased 
levels of circulating MDSCs.  In the placebo control, we also expect to see around 50% of participants 
with increased numbers of MDSCs.  Independent of the vaccine, we will also evaluate recurrence rates 
in MDSC high versus MDSC low individuals.  The trial is storing the pre-vaccination as well as the 
recurrent adenomas, and we plan to study the local microenvironment and infiltrating cells to identify if 
and how these features affect the vaccine response, systemic immunosuppression via MDSCs, and risk 
for adenoma recurrence.  
 
Proposed study of MUC-1 vaccine for prevention of lung cancer: Based on collected data and 
observations to date with the colorectal cancer prevention trials, our goal now is to test the feasibility of 
the MUC1 vaccine for prevention of other cancers.  In this proposal, we have chosen individuals at high 
risk for developing lung cancer, age 55-80, who have ≥30 pack year smoking history and are still smoking 
or quit < 1 year (current smokers ) or have quit 1-15 years prior to study registration (former smokers).  
These criteria match those individuals at high risk for lung cancer who are recommended to be screened 
for this malignancy by U.S. Preventive Services Task Force (USPSTF).27  Participants are also required to 
have low risk for the existence of malignancy based on Lung-RADs, Version 1.0.  
 
Preliminary data 
Completed feasibility trial at the University of Pittsburgh:  Between 2008 and 2012, we enrolled 40 
participants who received MUC1 – Poly ICLC vaccine at 0, 2, and 10 weeks and antibody titers were 
evaluated prior to each vaccination and at week 12, 28 and 52.16  In the 39 participants who received all 
three initial doses of vaccine, 17 (44%) had over a two-fold ratio increase at week 12, ten participants 
had ratios over 4.5 fold, and another 4 participants had a ratio increase from 1.4-2.0.  The kinetics of the 
responses were similar, with peak antibody levels generally occurring after the third injection.  As 
expected, circulating antibody levels tended to decline over the next year with clearance of the vaccine 
antigen.  The overall response rate of 44% was much higher than 2-3% reported for most therapeutic 
vaccines including MUC1 vaccines.  The non-responders to the vaccine, as was described above, had 
increased levels of circulating MDSCs that suppressed the ability of the vaccine to elicit immunity.  See 
Figure 2. 

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Response to Booster vaccine:  To test for the presence of a vaccine-
induced T cell memory response, participants received a booster dose 
of vaccine at 1 year.  Of the 16 participants who responded to the 
initial vaccination and received the booster, 12 (75%) had a two-fold 
ratio increase when comparing week 54 to week 52.  Three of the 4 
who did not have a two-fold elevation at week 54 had maintained high 
levels of antibody at week 52, hence did not manifest a 2-fold ratio 
increase at week 54.  Overall, the results suggest that responders 
established a T cell memory response to the MUC1 antigen.  In the 
proposed trial, we will not be administering a booster shot.  Since all 
the W12 responders in the previous trial also responded to the 1-year 
booster shot and none of the non-responders did, W52 would not add 
new information.  This also allows us to complete the study much 
faster. 
 
Adverse Events:  Over 150 vaccinations were administered and no 
adverse events above grade 1 were identified or unanticipated adverse 
events observed.  Most participants developed erythema with soreness 
at the injection site.  Some developed short-lived fever and muscle 
aches, which responded well to analgesics such as Tylenol.  We had 
nearly 100% compliance with the study protocol.  Participants were 
monitored with immunofluorescent ANA titers pre vaccination and at 1 
year.  No participants have developed a change in ANA titer, and no 
new autoimmune diseases were observed.  
 
Evaluation of Immune Non-Responders:  Lack of response to 
vaccination was correlated with high levels of circulating myeloid-derived suppressor cells but not to 
circulating T regulatory cells.  
 
Ongoing randomized placebo controlled multi-center trial:  The MAY2013-01-01 trial started in 2014 and 
in two years completed accrual of 102 evaluable participants, most of whom received the full course of 
the vaccine, W0, W2, W10, and were evaluated for post-vaccine IgG titers at W12.  Our preliminary data 
show over 30% responders so far and 70% non-responders who are either bona-fide non-responders or 
are in the placebo group (50%).  We have also evaluated MDSC levels and find a wide range, with some 
individuals having very high levels of circulating MDSC.  These are very preliminary results that will be 
possible to interpret only when the trial is unblinded.  What we can say with confidence at this point is 
that we have seen no adverse events. 
Abnormal MUC1 expression in bronchial dysplasia:  Even though abnormal MUC1 expression has been 
reported on various types of lung dysplasia, we wanted to confirm that in our laboratory.  From the 
Cancer Prevention Network (CPN), we obtained paraffin-fixed tissue sections from bronchial dysplasia 
biopsies that were collected in the context of the “Randomized, Phase IIb Trial of Sulindac in Smokers 
with Bronchial Dysplasia,” DCP Protocol # MAY03-1-02.  We received 8 samples, 4 of mild and 4 of 
moderate dysplasia.  By immunohistochemistry using two different anti-MUC1 antibodies, we found 
increased expression (as seen by antibody HMPV) and abnormal glycosylation (antibody 4H5) in all 
samples.  Figure 3 shows two examples of MUC1 expression in moderate dysplasia.  
Figure 2A:  Ratio response in 
MUC1 antibody. 
Figure 2B: Kinetics of response to 
vaccination at 0, 2, and 10 weeks 
(arrows under X axis) and to 
booster vaccine at Week 52. 

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The vaccine is based on the MUC1 antigen15 abnormally expressed on colon cancer and precancerous 
polyps, described in detail below.  The vaccine was administered to healthy individuals with an increased 
risk for colon cancer due to the history of adenomatous polyps.16  Based on the data from this pilot 
study, we have undertaken a multi-center, placebo-controlled efficacy trial of the same MUC1 vaccine 
and in the same type of high-risk individuals for colon cancer following removal of an advanced 
adenoma.  This ongoing trial is sponsored by NCI DCP and coordinated by CPN at the Mayo Clinic in 
Rochester, MN. The endpoints of the trial are safety, immunogenicity, and reduction of polyp 
recurrence.  Because MUC1 is abnormally expressed in lung cancer as well as pre-invasive and 
premalignant dysplasia,33 we propose to test this vaccine in current and former smokers who are 
considered to be at an increased risk for developing dysplasia that can progress to lung cancer. 
 
Chronic inflammation is a well-recognized hallmark of cancer.34 Cigarette smoking is a major risk factor 
for lung cancer development. Among the mechanisms by which smoking increases risk of lung cancer is 
increase in chronic inflammation.  An abundance of data demonstrates that chronic inflammation 
induces an immune-inhibitory environment conductive to cancer development. Release of 
immunosuppressive cytokines e.g. IL-6 or IL-10 is one of the mechanisms involved. High sensitivity C-
reactive protein (hsCRP) is another marker of inflammation and individuals with elevated hsCRP 
concentration have been shown to have increased risk of several inflammation-related cancers, 
especially lung cancer.35-37 
 
Results of a recent trial of anti-inflammatory therapy with canakinumab inhibiting interleukin 1β (IL-1β) 
reported reduction in lung cancer incidence among individuals with elevated hsCRP and IL-6 levels.38  In 
this report, those with increased concentrations of hsCRP and IL-6 had the highest risk for lung cancer 
and smokers along with those who had greatest reductions in hsCRP and IL-6 levels seemed to benefit 
most from canakinumab. Therefore, we plan to examine in an explanatory fashion whether or not 
MUC1/Poly-ICLC has an impact on hsCRP and interleukin-6 (IL-6) levels when assessed at Week 24 
compared to baseline. In addition, we will explore if baseline concentration of both inflammation-
related markers have any impact on ability to successfully vaccinate with MUC1/Poly-ICLC. These data, 
along with other exploratory studies planned in this trial, will inform selection of study target population 
for the next generation investigations.  
 
Increasing evidence suggests that tobacco and alcohol use are risk factors in the development of 
intraepithelial neoplasia and cancer. In addition, tobacco and alcohol use may adversely affect agent 
intervention, for example by altering the safety profile or metabolism of a drug. Standardized 
assessments of tobacco and alcohol use during clinical trials will aid in understanding the potential 
relationship between the use of these products and clinical endpoints or cancer prevention biomarkers. 
Therefore, NCI, DCP is including assessment of tobacco and alcohol use at baseline and Week 24, to 
determine the potential impact of tobacco and alcohol use on 1) treatment toxicity and symptom 
burden, and 2) the efficacy of treatment intervention. 
 
3. 
SUMMARY OF STUDY PLAN 
We propose to start with a pilot study that will test immunogenicity and safety of the vaccine in 
individuals at high risk for lung cancer.  Even though the two trials described above have given us 
information about immunogenicity and safety of this vaccine in individuals at risk for colon cancer, we 
cannot assume the same for individuals at risk for lung cancer.  We expect that smoking has led to the 
establishment of a long-term chronic inflammation in the lung of most potential participants, which is 
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the individuals eligible for the vaccine are expected to have ongoing chronic obstructive pulmonary 
disease (COPD), which has already been shown to expand numbers of circulating MDSCs creating an 
immunosuppressive microenvironment.39  This does not allow us to predict either the rate of the 
immune response or the level of vaccine immunogenicity in this population.  It is also possible that the 
extent of inflammation in the lung could make the lung more vulnerable to the effects of a strong 
adaptive immune response.  Based on the safety profile of this vaccine in lung cancer trials, where the 
cancer-bearing lung is also a chronically inflamed organ, we do not expect any adverse effects.  
However, in none of these trials has very strong immunity been elicited by the vaccine.  Thus, 
immunogenicity and safety have not yet been properly tested in this population.  This pilot study will 
provide us with the safety and immunogenicity data that will decide whether testing of this vaccine 
could subsequently proceed to the placebo-controlled efficacy trial(s) for the prevention of lung cancer.   
 
This is a pilot trial designed to evaluate co-primary endpoints: the preliminary immunogenicity in 
response to the MUC1 vaccine against abnormal MUC1 (assessed at 12 Weeks) and the safety (assessed 
at up to 24 weeks) in current and former smokers, who are at high risk for development of lung cancer.  
Immune response will also be evaluated at Week 24. We expect to consent and screen up to 85 
participants in order to have approximately 40 evaluable participants with baseline and 12-week 
immunogenicity assessments.  This includes a 41% rate of ineligibility and 20% rate of drop 
out/otherwise not evaluable.  The projected rates of ineligibility, dropout, and otherwise not evaluable 
are based on experience with the prior MUC1 protocol and other engagements with the proposed target 
population.  If the projected rates of ineligibility and drop out prove to be optimistic, it should be noted 
that even with 30 evaluable participants, statistical power will be sufficient for the purposes of this pilot 
study. 
 
4. 
PARTICIPANT SELECTION 
 
4.1 
Pre-Registration Inclusion Criteria 
 
4.1.1 
Smoking history of ≥30 pack-years AND either current smoker (still smoking or quit < 1 year prior 
to pre-registration) OR former smoker (quit 1-15 years prior to pre-registration).  Note:  Pack years is 
determined by multiplying the number of packs smoked per day by the number of years smoked. 
 
4.1.2 
Ages 55-80 years  
 
4.1.3 
ECOG performance status ≤1 (See Appendix A) 
 
4.1.4 
CT scan of the chest done ≤ 6 months prior to pre-registration showing either negative findings 
(no nodules) OR solid or part-solid nodules < 6 mm in size OR consistent with < 1% probability of 
malignancy, Lung-RADs Version 1.0 
 
4.1.5 
Willingness to employ adequate contraception, if applicable.  Note:  the effects of MUC1/Poly-
ICLC on the developing human fetus at the recommended therapeutic dose are unknown. For this 
reason, women of child-bearing potential and men must agree to use adequate contraception 
(hormonal or barrier method of birth control; abstinence) 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 study physician immediately. 
 

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4.1.6    Ability to understand and the willingness to sign a written informed consent document 
4.2 
Pre-Registration Exclusion Criteria 
 
4.2.1 
History of any malignancy. Exceptions: Non-melanoma skin cancer or CIS of the cervix  
 
4.2.2 
Known Hepatitis B or C   
 
4.2.3 
Receiving any other investigational agents 
 
 
4.2.4     Any prior investigational immune therapy, such as for lung cancer prevention or treatment or for 
CIS of the cervix 
 
4.2.5     Use of oral or systemic steroids or other systemic anti-immune therapy ≤ 90 days prior to pre-
registration.  Note:  Use of inhaled/nasal steroids and local steroid injections for pain control are not 
exclusionary. 
 
4.2.6     Known HIV 
 
4.2.7     Known autoimmune disease 
 
4.2.8 
Known Non-alcoholic steatohepatitis (NASH) or Non-alcoholic fatty liver disease (NAFLD) 
 
4.2.9     History of allergic reactions attributed to compounds of similar chemical or biologic composition 
to MUC1/Poly-ICLC 
 
4.2.10 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. 
 
4.3       Registration Inclusion Criteria 
 
4.3.1 Participants must have normal organ and marrow function as defined below: 
Leukocytes (WBC) 
≥ 3,000/microliter 
Neutrophils (ANC) 
≥ 1,500/microliter 
Platelets 
 
≥ 100,000/microliter 
Total bilirubin  
≤ 1.5 x institutional upper limit of normal (ULN) Note:  Higher 
  
 
 
total bilirubin levels (≤ 3 mg/dL) can be allowed if due to known 
  
 
 
benign liver condition, i.e. Gilbert’s. 
AST (SGOT) 
 
≤ 1.5 × institutional upper limit of normal (ULN) 
ALT (SGPT) 
 
≤ 1.5 × institutional upper limit of normal (ULN) 
Creatinine 
 
≤ institutional upper limit of normal (ULN) 
 
4.4     Registration Exclusion Criteria 
 
4.4.1 
Any positive ANA titer above 1:160, even in an asymptomatic individual.   Note:  Weakly positive 
ANA defined as ANA titers up to 1:160 maximum (≤ 1:160) will be acceptable in an asymptomatic 
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4.2.2 
Pregnant or breast feeding.  Note:  Pregnant women are excluded from this study because the 
MUC1/Poly-ICLC vaccine may have the potential for teratogenic or abortifacient effects. Because there is 
an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with 
MUC1/Poly-ICLC vaccine, breastfeeding should be discontinued if the mother is treated with the 
vaccine. 
 
4.5   
Inclusion of Women and Minorities 
 
Both men and women (as applicable) and members of all races and ethnic groups are eligible for this 
trial. Please refer to the Recruitment, Retention, and Adherence (RR&A) Plan for details. 
 
4.6 
Recruitment and Retention Plan 
 
Each Participating Organization will be required to develop and submit a study- and site-specific RR&A 
plan for the purposes of insuring equal access to the clinical trial by individuals of all genders, races, and 
ethnic groups and for attaining the organization’s accrual target.  Participating Organizations will use the 
RR&A Plan Worksheet as the basis for their plans.  At a minimum, these plans will be reviewed annually.  
 
In summary, participants will be identified from the lung health, smoking, thoracic clinics, and/or CT 
screening programs at The University of Pittsburgh Medical Center and the Mayo Clinic in Rochester, 
Minnesota.  Individuals at high risk for developing cancer but at low risk for having cancer will be 
recruited by the site study teams according to their site-specific RR&A plans and utilizing recruitment 
materials approved by NCI, DCP, the CIRB, and any applicable local entities.  Accrual will be closely 
monitored by the Consortium Lead Organization and NCI, DCP.  Accrual plans will be revised regularly 
and as needed to complete the study in an acceptable time frame. 
 
5. 
AGENT ADMINISTRATION 
 
Intervention will be administered on an outpatient basis. Reported adverse events (AEs) and potential 
risks are described in Section 6.2.  
 
5.1 
Dose Regimen and Dose Groups 
 
The MUC1 peptide is manufactured at the FDA certified peptide facility of the University of Pittsburgh. 
The vaccine will consist of 100 micrograms of the MUC1 100mer peptide dissolved in 50 micro-liters of 
sterile saline, admixed with 500 micrograms of the adjuvant poly-ICLC (Hiltonol®) in 250 microliters 
volume, for a total injection volume of 300 microliters. Poly-ICLC is a TLR3 agonist, a synthetic, non-
replicating dsRNA with no specific genetic message, which acts as a viral-mimic and activator of diverse 
elements of both the innate immune response and of adaptive immunity.40  
 
5.2    MUC1/Poly-ICLC Vaccine Administration 
 
The vaccine will be administered by appropriate site personnel subcutaneously in the upper arm 
(preferably) or in the anterior thigh approximately 20 cm inferior to the inguinal ligament, if injection in 
the upper arm(s) is not possible. The vaccine will be administered into the same upper arm on all 3 

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occasions for vaccine delivery. The vaccine site may demonstrate erythema and/or tenderness after 
administration. This erythema and/or tenderness can persist even to the timing of the next vaccine 
dosing.  Erythema is not a contraindication to repeat vaccination. However, persisting injection site 
tenderness (and/or other local injection site reaction) may, at the discretion of the investigator, be a 
reason to administer subsequent, scheduled vaccine into the opposite upper arm. Similarly, the 3rd 
vaccine administration can be given into the same upper arm as the previous (2nd) vaccine or into the 
opposite upper arm (the same upper arm where the initial 1st vaccine was given). Also, at the discretion 
of the investigator, repeat vaccination may be delayed, but not to exceed the protocol limits (See 
section 7.1). It is also possible to inject the vaccine into the thigh(s), if necessary. 
 
5.3 
Run-in Procedures  
 
Not applicable. 
 
5.4 
Contraindications 
 
If a study participant is prescribed corticosteroids, immunomodulators, or any medications listed as 
exclusionary (Section 4.2) during the course of the study, the participant will be taken off agent (no 
further vaccine administrations) but followed per protocol through the Follow Up telephone call. 
 
5.5 
Concomitant Medications 
 
All medications (prescription and over-the-counter), and vitamin, herbal, and mineral supplements 
taken by the participant will be documented on the concomitant medication CRF and will include:  start 
and stop date, dose and route of administration, and indication. Medications taken for a procedure 
(e.g., biopsy) will also be included. 
 
5.6 
Dose Modification 
 
There will be no dose reductions.  A vaccine administration can be withheld: 
• At any time deemed appropriate, based on the best clinical judgment of the treating physician.  
Vaccine administration can be withheld for up to a week. 
• For any Grade 2 increases in liver function tests, pancreatic function tests, or ANA titers, vaccine 
administration should be withheld until test results resolve to Grade 1 or baseline. 
• The second vaccine administration can be withheld for up to one week and the third vaccine 
administration can be withheld for up to 2 weeks.  These individuals will still be considered 
evaluable for the primary endpoint.  
• 
If dose 2 is delayed by ≤ 1 week, dose 3 will still be scheduled at week 10.  If dose 2 is not 
administered within 1 week of the scheduled time point, the participant will be considered “off 
agent” but will be followed per protocol.  Dose 3 will not be given if dose 2 was not 
administered within the planned schedule. 
 
5.7 
Adherence/Compliance 
 
5.7.1  All vaccine will be administered by appropriately trained personnel at each site.  
Vaccine administration will be documented on the Intervention Administration CRF.   
 

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5.7.2      Individuals who receive the Week 0, Week 2, and Week 10 injections will be considered 
evaluable for the primary endpoint.  If subjects receive at least 1 but not all 3 injections, they will still be 
considered evaluable for secondary endpoints.   
 
6. 
PHARMACEUTICAL INFORMATION 
 
6.1 
MUC1 Vaccine (IND # 
, NCI, Division of Cancer Prevention)   
 
MUC1 Peptide 
The MUC1 peptide is composed of 100 amino acids (aa), representing five 20aa-long tandem repeats of 
the MUC1 VNTR region: H2N-(GVTSAPDTRPAPGSTAPPAH)5-CONH2. The peptide is synthesized on a rapid 
multiple peptide synthesizer (Dupont NEN) in a dedicated facility under a strict and fully certified 
procedure and using reagents with a defined expiration date.  The peptide is highly hydrophilic and for 
testing as well as injection, it is dissolved in sterile saline. The peptide is tested for pyrogenicity and 
safety in guinea pigs, mice, and rabbits in accordance with an FDA approved protocol in a commercial 
facility.  Once tested negative, it is aliquoted in small freezer vials containing one injection volume (100 
mcg lyophilized peptide in 0.05 mL of sterile saline).  Two percent of vials are sampled randomly for 
sterility testing in the University of Pittsburgh Medical center Microbiology Laboratories.  Both 7 and 14-
day sterility results are recorded.  Peptide synthesis procedure, safety, pyrogenicity and sterility are 
contained in detail in Dr. Schoen’s IND application to the FDA cross referenced by NCI, DCP.  This peptide 
and all these procedures have been previously examined and approved by the FDA six times in six 
different IND applications.  For administration as a vaccine, the peptide will be admixed with the POLY-
ICLC adjuvant described above and below and injected subcutaneously as described above. 
 
Poly ICLC 
Poly-ICLC is supplied by Oncovir in vials containing 1 mL of 2 mg/mL opalescent white suspension. Poly- 
ICLC is withdrawn from the vial under sterile conditions and is to be administered intramuscularly, 
subcutaneously or intranasally as supplied. It can also be diluted with normal saline. 
 
Each vial Poly-ICLC will be labeled with the following information: 
• Drug Name 
• Concentration 
• Lot Number 
• Date of Manufacture 
• Manufacturer 
• Investigational Use Statement 
 
Low-dose Poly-ICLC administered IM or SC or intranasally has been well tolerated in clinical trials of 
patients with brain tumors, other cancers, multiple sclerosis, and in normal volunteers. Multiple 
additional trials have used it in combination with various cancer or HIV vaccines. The most common 
adverse events experienced in these studies have been transient discomfort at the injection site and 
transient malaise. Subcutaneous injection may result in a transient erythematous skin reaction. 
Preliminary findings from these trials suggest that low-dose Poly-ICLC may be effective in treating 
various tumors and further study is warranted. 
 
Poly ICLC synthesis, procedure, safety, pyrogenicity, and sterility are contained in detail in the Oncovir 
IND and DMF to the FDA cross-referenced by NCI, DCP. 

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6.2 
Reported Adverse Events and Potential Risks 
 
A preliminary human clinical study with the MUC1 100mer vaccine was conducted in subjects with a 
history of advanced adenoma.16 Forty subjects received 100 µg of MUC1 100mer admixed with 
polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (Poly-ICLC) adjuvant at 0, 2, and 10 
weeks; antibody titers were evaluated prior to each vaccination and at weeks 12, 28, and 52. More than 
150 vaccinations were administered in this study. No adverse events (AEs) above CTCAE (v3.0) grade 1 
were identified, and no unanticipated AEs were observed. AEs related to vaccination included erythema, 
experienced by 87.5% of subjects (35 out of 40), discomfort at the injection site (80%, 32 subjects), and 
flu-like symptoms (37.5%, 15 subjects), which responded well to analgesics such as Tylenol. No subjects 
developed a change in anti-nuclear antibody (ANA) titer at one year, and no new autoimmune diseases 
were observed.  
 
The MUC1 vaccine was also assessed in 16 pancreatic cancer patients who were candidates for curative 
resection due to early diagnosis.20 These patients were considered better vaccine candidates because of 
a lower tumor burden and no immunotoxicity from previous chemotherapy. Subjects received four 
different doses of the MUC1 100mer peptide vaccine (100, 300, 1000, and 3000 µg, four subjects/group) 
admixed with SB-AS2 adjuvant every three weeks for three doses. The vaccine was well tolerated with 
most subjects experiencing mild AEs, including flu-like symptoms (grade 1, 25%), and tenderness (grade 
1, 38%) and erythema (grade 1, 31%; grade 2, 6%) at the injection site. No grade 3/4 AEs were reported. 
 
A phase 1 trial with MUC1 105mer peptide vaccine accrued 63 subjects with advanced colon, pancreatic, 
and breast cancers.41  Subjects were vaccinated with 100 µg of a MUC1 peptide, consisting of 105 amino 
acids representing a little more than 5 tandem repeats from the extracellular VNTR, admixed with BCG 
as adjuvant. Two booster vaccines were administered at three-week intervals. The vaccine was well 
tolerated, with most subjects (98%) experiencing local ulceration at the injection site, fever, chills, and 
night sweats, all related to BCG, which is no longer used as adjuvant. 
 
MUC1 100mer plus Poly-ICLC vaccine was previously tested in a phase 1/2 trial in metastatic prostate 
cancer. In this trial, Poly-ICLC was used in two different ways, as an adjuvant as well as an immune 
modifier. Patients were pretreated for two weeks prior to the MUC1/poly-ICLC vaccination with an 
intravenous injection three times/week with one of two high doses of Poly-ICLC, 25 µg/kg or 50 µg/kg; 
this was continued until disease progression. Two weeks after starting intravenous Poly-ICLC, patients 
were given the MUC1 vaccine with Poly-ICLC as adjuvant, as a low dose of 500 µg total per injection, 
subcutaneously; three injections were administered at three-week intervals. A total of 14 patients were 
treated; 88% experienced grade 1 toxicity, the most common being injection site reaction (93%). Eight 
patients experienced grade 2 toxicity (fatigue and fever), and two patients had grade 3 toxicity (fever 
and transient neurological symptoms) correlating with the start of iv injections of high doses of Poly-ICLC 
prior to vaccination. These symptoms were readily controlled and resolved. There were no grade 4/5 
AEs.   
 
MUC1/Poly-ICLC vaccine was administered to three patients with advanced lung cancer and quickly 
progressing disease. Two patients received only one injection before succumbing to their disease. The 
third patient received boosters every three months for a total of three years, and developed anti-MUC1 
antibodies while experiencing only grade 1 toxicity (redness and inflammation at the injection site). 
 

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One patient with metastatic lung cancer is currently being treated on an expanded access protocol and 
is receiving the MUC1/Poly-ICLC vaccine on the same schedule as the one followed in the prophylactic 
setting in advanced adenoma (week 0, 2, and week 10). The patient has generated a good antibody 
response and is now getting regular boosters every three months. The only reported AEs are grade 1 
toxicity at the injection site, and long-term disease stability is reported. 
 
An NCI, DCP-sponsored randomized, double-blind, placebo-controlled trial of MUC1-Poly ICLC vaccine in 
participants with newly diagnosed advanced adenomas is ongoing. Subjects are randomly assigned to 
receive either MUC1-Poly ICLC vaccine or normal saline injections at week 0, 2, and 10, with a booster 
injection at week 53. In 103 subjects evaluable for toxicity to date, the most commonly reported AEs 
were grade 1/2 injection site reactions (29 subjects, 28.2%) and grade 1 influenza-like illness (eight, 
7.8%).  
 
In one subject given the MUC1 vaccine in the DCP adenoma study, grade 1 elevated liver enzymes 
(alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) were observed two weeks after 
the initial injection. The DCP Medical Monitor considered this to be a serious adverse event (SAE), 
possibly related and unexpected for the study agent, thus qualifying it as an IND safety report. The data 
in this case suggest that the increased hepatic enzymes may be related to MUC1 vaccine and/or the 
adjuvant poly-ICLC (Hiltonol).  
 
The Poly-ICLC Investigator’s Brochure provides data from high dose (unspecified) Poly-ICLC cancer trials 
indicating that modest reversible hepatic enzyme elevations can occur after drug administration. In a 
trial of intravenous Poly-ICLC (about 100 μg/kg) administered to multiple sclerosis (MS) patients, 
transient, modest elevations of AST and ALT occurred after 84% of 127 infusions, and increased lactate 
dehydrogenase (LDH) and alkaline phosphatase occurred after 52% of the infusions. The event in this 
DCP-sponsored trial was considered unexpected because the adjuvant dose was much lower (3.95 
μg/kg) and administered via a different route (subcutaneous) than in the MS study, as well as 
administered with the MUC1 vaccine. Also, although the subject had a relevant past history of 
nonalcoholic steatohepatitis (NASH) with a risk factor of obesity, the MUC1 vaccine and/or the adjuvant 
Poly-ICLC could not be ruled out as a cause of the event due to the timing. No similar events have been 
reported in the study or in the four prior completed studies described in the Investigator’s Brochure. 
Individuals with a diagnosis of NASH and a NAFLD (nonalcoholic fatty liver disease) activity score (NAS) 
≥5 are excluded from the current study in response to this event. Other SAEs reported in the ongoing 
DCP study are considered not related to study agent. 
 
 
 
 
 
 
 
 
 
 
 
 

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6.4 
Agent Distribution 
 
Agents will only be released by NCI, DCP after documentation of CIRB approval of the DCP-approved 
protocol and consent is provided to DCP and the collection of all Essential Documents is complete (see 
DCP website for description of Essential Documents).  
 
The Investigator, or a responsible party designated by the Investigator, must maintain a careful record of 
the inventory and disposition of all agents using NCI Drug Accountability Record Form (DARF) or 
comparable institutional form. The investigator or designee is required to maintain adequate records of 
receipt, dispensing, and final disposition of study agent. Include on receipt record from whom the agent 
was received and to whom study agent was shipped, date, quantity, and batch or lot number. On 
dispensing record, note quantities and dates study agent was dispensed to and returned by each 
participant.  
 
6.5  
Agent Accountability 
 
The Investigator, or a responsible party designated by the Investigator, must maintain a careful record of 
the inventory and disposition of all agents received from DCP using the NCI Drug Accountability Record 
Form (DARF). The Investigator is required to maintain adequate records of receipt, dispensing and final 
disposition of study agent. This responsibility will be delegated to the Participating Organization 
pharmacist.  Include on receipt record from whom the agent was received and to whom study agent was 
shipped, date, quantity and batch or lot number. On dispensing record, note quantities and dates study 
agent was dispensed to and returned by each participant.  
 
6.6 
Packaging and Labeling 
 
The participating organization pharmacy personnel will be required to label the injection supplied for 
each participant.  Each injection should be labeled according to institutional guidelines.   The label 
should define the injection as MUC 1 100mcg/0.05mL w. poly-ICLC 500mcg/0.25mL.  The label should 
also include the date of preparation, the route of administration, and the study name.  The label may 
also include other information, such as the time of expiration, as required by local or state regulations. 
 
6.7 
Storage 
 
The MUC-1 vaccine will be stored frozen at-70 to -80o C until mixed for injection.  MUC1 Vaccine will be 
shipped on dry-ice overnight to each site.  Participating organizations are required to store the vaccine 
in a -70 to -80o freezer upon receipt. 
 
Poly-ICLC is stable at room temperature for brief periods (days). It is normally refrigerated at about 40oF 
(2-8°C) but should not be frozen.  Poly-ICLC will be shipped at ambient temperature overnight to each 
participating site.   It is to be stored in the refrigerator upon receipt.  
 
 
 
 
 
 

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6.8 
Pre-Registration and Registration 
 
6.8.1 Participant Pre-Registration 
 
6.8.1.1 To pre-register a participant, the participating site will send the completed, signed, and 
dated Pre-Registration Eligibility Checklist, to the CPN Registration Office (Email: 
random01@mayo.edu; Fax: 507-284-0885) to pre-register all participants.  The CPN Registration 
Office will enter the information into the CPN-hosted database.   A unique participant identification 
number (PID) will be assigned. No study-related activities may take place until pre-registration has 
taken place. 
 
6.8.1.2 At the time of pre-registration, the following will also be verified: 
• 
CIRB (local context subcommittee) approval for the registering institution 
• 
Participant eligibility (including existence of a signed informed consent document) 
• 
Existence of a signed authorization for use and disclosure of protected health information  
(USA Institutions only) 
• 
Study agent is available and Drug Shipment Authorization has been granted to the 
registering site 
• 
The following will also be recorded: 
o Participant has/has not given permission for blood samples to be collected and that 
these samples and related information may be used for optional laboratory studies. 
o Participant has/has not given permission for the study doctors to contact them or 
their physician to see if they wish to learn about the results from the optional 
studies. 
o Participant has/has not given permission for blood samples and related information 
to be kept in a Biobank for use in future health research. 
o Participant has/has not given permission for information from their alcohol and 
tobacco use assessments to be used for future health research 
o Participant has/has not given permission to send blood sample(s) and related 
information to researchers at outside institutions. 
o Participant has/has not given permission to their study doctors (or their 
representative) to contact them to see if they wish to participate in research in the 
future. 
6.8.1.3   Baseline (screening) evaluations must be completed within the guidelines specified on 
the Schedule of Events (See Section 7.1). 
6.8.1.4 Registration Office personnel will automatically register participants separately to the 
translational components of the study (See Section 13). 
 
6.8.2 Registration 
 
6.8.2.1 To register a participant, the participating site will send the completed, signed, and dated 
Registration Eligibility Checklist to the CPN Registration Office (Email: random01@mayo.edu; Fax: 
507-284-0885).  The CPN Registration Office will enter the information into the CPN-hosted 
database.  For randomization details, see Section 13.2.  
 
6.8.2.2 Intervention on this protocol must commence at a CPN institution under the supervision of a 
CPN clinician. 

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6.8.2.3 Intervention cannot begin prior to Registration and must begin ≤ 14 days after Registration. 
 
       6.8.2.4   Descriptive Factors:   
• 
Participating organization: University of Pittsburgh versus Mayo Clinic 
• 
Gender: Male versus female 
• 
Smoking status: Current versus former  
 
6.9 
Blinding and Unblinding Methods 
 
Not applicable  
 
6.10 
Agent Destruction/Disposal 
 
At the completion of investigation or after completion of the site pharmacy final close out visit report by 
the CPN Compliance Coordinator, all unused study agent will be returned to the University of Pittsburgh. 
The University of Pittsburgh will supply instructions, shipping supplies, shipping bills, and other items 
necessary for the return shipment.  

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1. Vital signs include height (screening only), weight, temperature, blood pressure, heart rate, respiratory rate. 
2. Hematology testing (evaluated at local labs) includes CBC with 5-part differential and platelets. 
3. Blood chemistry tests (evaluated at local labs) include:  potassium, sodium, chloride, bicarbonate, creatinine, serum glucose, BUN, total 
bilirubin, alkaline phosphatase, AST/SGOT, ALT/SGPT, uric acid, amylase, lipase, and albumin.  At the screening, Week 4, and Week 24 
visits only, blood testing will also include antinuclear antibody (ANA).  Optional research blood will be collected at screening and Week 
24, if participant consent is provided. 
4. Testing (evaluated locally) includes spirometry, including graphic record, total and timed vital capacity, expiratory flow rate 
measurement, with or without maximal voluntary ventilation, and pulmonary diffusing capacity. 
5. Immunological testing for antibody responses to MUC1 (See Section 9.1).   
6. All blood testing for secondary and exploratory endpoints will utilize plasma remaining after the immunological studies are complete 
with the exception of high sensitivity C-reactive protein (hsCRP).  For individuals accrued prior to protocol Amendment 2, levels of hsCRP 
will be tested at baseline and Week 24 using frozen plasma remaining from the blood draw for immunological studies (See footnote #5 
above).   Beginning with Amendment 2, one extra blood specimen will be collected, processed into serum, and stored until the end of 
the study for hsCRP. 
7. Where applicable, blood draws and AE assessments will precede vaccine administration (See Section 7.4). 
8. If any adverse events have not resolved at the time of the Week 24 visit, an optional follow up phone call may take place at Week 28 (+/- 
7 days). 

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7.2 
Baseline Testing/Pre-study Evaluation 
 
After participants have been informed about the study and have signed the informed consent 
document, they will be pre-registered and assigned a unique participant identification number (PID).  
 
They will then undergo initial screening tests and procedures.  The order in which these tests and 
procedures is conducted is flexible within the designated study timelines and should be consistent with 
good clinical practice and institutional policies and procedures.  These tests and procedures include a 
physical exam, documentation of medical/surgical history, alcohol and tobacco use assessments, review 
of clinical CT imaging, and documentation of any existing baseline symptoms, allergies, concomitant 
medications, and baseline blood tests.  Baseline blood tests include ANA, CBC with 5-part differential 
and platelets, potassium, sodium, chloride, bicarbonate, creatinine, serum glucose, BUN, total bilirubin, 
alkaline phosphatase, uric acid, AST/SGOT, ALT/SGPT, albumin, amylase, lipase, and an optional 
additional specimen for future research.  Blood will also be drawn at baseline/screening for the immune 
assays and exploratory endpoints.  A urine cotinine test will be performed.  Pulmonary function testing 
includes spirometry, including graphic record, total and timed vital capacity, expiratory flow rate 
measurement, with or without maximal voluntary ventilation and pulmonary diffusing capacity.  A urine 
pregnancy test will be administered, if applicable. 
 
If participants are eligible and willing to participate, they will be registered to the study. 
 
7.3 
Evaluation During Study Intervention 
 
Vaccine will be administered at Weeks 0, 2, and 10.  Participants will be monitored for at least 30 
minutes after each injection for possible emergent side effects. 
 
Prior to vaccine administration: 
• 
Females of childbearing potential will be required to document negative pregnancy test. 
• 
Blood will be drawn for safety and/or immune response, as applicable (See Section 7.1 and see 
below). 
• 
Adverse events and concomitant medications will be assessed (See Section 11.1 for details). 
• 
Vital signs will be evaluated (temperature, blood pressure, heart and respiratory rates, and 
weight) 
• 
Blood testing results will be reviewed by the treating physician for clinical significance and 
possible indications of toxicity.   
 
Immune response will be tested at Weeks 2, 4, and 12.  A repeat ANA titer will be drawn at Week 4. 
Blood tests to monitor toxicity will be conducted at Weeks 2, 4, 10, and 12.  Urine cotinine will be 
monitored at Week 12.    
 
Adverse events will be evaluated during all contacts with the participants, with emphasis on AE 
evaluation two weeks after each injection (See Section 11.1 for details).  Possible adverse events and 
concomitant medication information will be captured by telephone at Weeks 16 and 20.   
 
 
 
 

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7.4 
Evaluation at Completion of Study Intervention (or early termination) 
 
The post-intervention evaluation will take place at Week 24 (+/- 7 days). The order in which these tests 
and procedures is conducted is flexible within the designated study timelines and should be consistent 
with good clinical practice and institutional policies and procedures.  These tests and procedures include 
a physical exam, review of adverse events, and concomitant medications, alcohol and tobacco use 
follow-up assessments, and blood tests.  Blood tests include CBC with 5-part differential and platelets, 
potassium, sodium, chloride, bicarbonate, creatinine, serum glucose, BUN, total bilirubin, alkaline 
phosphatase, uric acid, AST/SGOT, ALT/SGPT, albumin, amylase, lipase, and ANA.  Blood will also be 
drawn for the immune assays and exploratory endpoints. An optional additional blood specimen will be 
collected for future research, if consent was provided. A urine cotinine test will be performed.  
Pulmonary function testing includes spirometry, including graphic record, total and timed vital capacity, 
expiratory flow rate measurement, with or without maximal voluntary ventilation, and pulmonary 
diffusing capacity.   The Was It Worth It (WIWI) Questionnaire will also be administered. If the 
participant provides consent, the data from this questionnaire will be included in the central Quality of 
Life database (along with demographic information) that is accessible to non-study investigators after 
CIRB approval.  
 
7.5 
Post-intervention Follow-up Period 
 
If any adverse events have not resolved at the time of the Week 24 visit, a follow up phone call may take 
place at Week 28 (+/- 14 days).   Concomitant medications will be recorded.  Adverse events will be 
followed according to institutional standards of good clinical practice.   
 
7.6 
Methods for Clinical Procedures 
 
See Section 5.2 for vaccine preparation and administration procedures. 
 
8.  
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION 
 
8.1 
Primary Endpoint 
 
See Section 13.4.  
 
8.2 
Secondary Endpoints 
 
See Section 13.5. 
 
8.3 
Off-Agent Criteria  
 
Participants may stop taking the study agent due to: completion of the planned intervention period, 
development and/or continuation of an adverse event or serious adverse event, inadequate agent 
supply, noncompliance, use of concomitant medications, medical contraindication, refusal, ineligibility 
(see Section 8.4), major treatment violation (see Section 8.4) or alternative treatment. Participants will 
continue to be followed, if possible, for safety according to the intended schedule of events (see Section 
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Participants discontinuing the planned intervention prematurely will be encouraged to complete the 
Post-Intervention Evaluation tests and procedures as appropriate (if participant does not refuse, is not 
lost to follow-up, or unless it is clinically contraindicated). See Section 8.4 for further details as to data 
submission for participants deemed Ineligible after starting treatment or classified as a Major Treatment 
Violation (i.e., protocol requirements regarding intervention during the first week post-registration were 
severely violated). In such cases, all data and all on-study materials, collected up until the point of 
confirmation of ineligibility or major violation status must be submitted. 
 
8.4 
Off-Study Criteria 
 
Participants may go “Off-Study” for the following reasons: development or continuation of an adverse 
event or serious adverse event, death, lost to follow-up, participant withdrawal, physician decision, 
protocol violation, completion of study, or other (with detailed comments provided). Reason(s) will be 
noted in the participant’s research records, with the primary reason clearly identified. The participant 
will be classified as (Off Study/Off Agent). Data submission and follow-up after participants are 
determined to be a screen failure or “Off-Study/Off-Agent” for specific situations is noted below: 
 
Ineligible: A registered participant is deemed ineligible if the participant does not satisfy each 
and every eligibility criterion for study entry. 
• 
If participants received study intervention, on-study materials and all data up until the 
point of confirmation of ineligibility will be submitted. 
• 
If participants did not receive study intervention, on-study materials must be submitted. No 
further data submission is necessary. No follow-up is required. 
 
Major Treatment Violation: A registered participant is deemed as being in major treatment violation by 
the coordinating center, if the participant’s very first treatment/intervention administration is so grossly 
administered in error, that the participant’s data can no longer be used for the primary endpoint. These 
cases are typically rare. 
• 
On-study material and all data up until the point of confirmation of a major violation must 
be submitted. 
 
Cancel: A registered participant is deemed a cancel if he/she refuses the study before any study 
intervention is given.   
• 
On-study material must be submitted. No further data submission is necessary.  No follow-
up is required. 
 
8.5 
Study Termination 
 
NCI, DCP as the study sponsor has the right to discontinue the study at any time.  
 
 
 
 
 
 
 

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9. 
CORRELATIVE/SPECIAL STUDIES 
 
9.1 
Rationale for Methodology Selection 
 
The most appropriate biomarker of vaccine efficacy is the immune response.  We will measure the 
major T cell dependent anti-MUC1 antibody IgG isotype that requires MUC1 specific T cells to promote 
isotype switching by B cells from IgM.  We will largely focus on IgG, as that antibody isotype is easier to 
measure and more reproducibly induced.  The biospecimen repository archive will include plasma and 
PBMC for immunologic and other assays, such as the frequency and quality of antigen-specific T cells 
induced by the vaccine, and changes in the serum cytokine and chemokine profiles.  
 
The MUC1 ELISA is an established assay that has been used to monitor many clinical trials as well as IgG 
response in large cohorts of patients on other studies.  It has been validated as highly reproducible.  The 
set-up includes positive and negative control anti-MUC1 antibodies that allow comparison of results 
between different studies.  Nevertheless, in this trial, each patient will also be his/her own control as we 
will compare post-vaccination titers with pre-vaccination baseline.  All time points will be assayed 
simultaneously and multiple times.   
 
Immune Assays:  Upon receipt of the overnight shipment or immediately after collection, heparinized 
blood will be centrifuged over a density gradient (Ficoll) to separate the plasma and PBMC. Plasma will 
be collected, aliquoted, and stored at -20oC.  PBMC will be washed several times, aliquoted, slowly 
frozen to -70 to -80oC in human serum with 20% DMSO and stored in the vapor phase of liquid nitrogen.  
 
Measurement of the vaccine-induced anti-MUC1 IgG will be determined by the Enzyme-Linked 
Immunosorbent Assay (ELISA) that was established in Dr. Finn’s laboratory and successfully used to 
measure anti-MUC1 responses in humans and mice.  The procedure is as follows: Immulon 4 (Thermo-
Fisher Scientific, MA) microtiter plates are coated overnight at 4ºC with 1μg of synthetic MUC1 100mer 
peptide (vaccine antigen) dissolved in 0.9% Dulbecco phosphate buffered saline (PBS).  Corresponding 
control plates receive PBS but no antigen. The plates are washed three times with and incubated with 
2.5% bovine serum albumin (BSA) in PBS (PBS-BSA) to fully coat the microtiter plate wells with protein 
and block non-specific binding. PBS-BSA is removed and plasma diluted in PBS-BSA added to the wells.  
After one-hour incubation at room temperature the plates are washed five times with PBS with 0.1% 
tween-20 (Sigma-Aldrich, MO), and alkaline phosphatase-conjugated anti-human IgG secondary 
antibody (Sigma-Aldrich) in PBS-BSA added.  Following one-hour incubation, the plates are washed five 
times and the substrate, p-nitrophenyl phosphate (Sigma-Aldrich), added to each well. The reaction is 
terminated after one hour by adding 0.5M NaOH. The results are read at optical density (OD) 405nm on 
a spectrophotometer. The OD values from the control wells containing no antigen are subtracted from 
the OD values in test wells coated with peptide. Every sample is assayed multiple times at multiple 
dilutions, in at least triplicate wells.  The results can be expressed wither as OD values or control 
antibody of a known titer, included in the assay, is used to convert the OD values to titers.   
 
For detecting Myeloid-Derived Suppressor Cells (MDSC), PBMC will be thawed and stained with APC-
labeled mouse anti-human CD11b antibody (clone: ICRF44, BD Biosciences), PE-Cyanine 7 (PE-Cy7) 
labeled mouse anti human CD14 antibody (clone: M5E2, BD Biosciences), PE -labeled mouse anti human 
CD33 antibody (clone: WM53, BD Biosciences) and FITC-labeled mouse anti human HLA-DR antibody 
(clone: G46-6, BD Biosciences). MDSC will be defined by flow cytometry as CD11b+ CD33+/low HLA-DR-/low 
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9.2 
Comparable Methods 
 
This study will employ procedures that have been validated previously for clinical use. 
 
10. 
SPECIMEN MANAGEMENT  
 
10.1 
Laboratories 
 
Clinical laboratory analyses will take place at each Participating Organizations’ CAP-certified laboratory. 
 
Immunology analyses will take place in the laboratory facilities overseen by Olivera Finn, Ph.D. at the 
University of Pittsburgh: 
 
E1000-17B Biomedical Science Tower 
200 Lothrop Street, Pittsburgh, PA. 15261 
Phone:  412-648-8561 or 412-648-9817; Fax:  412-383-8098; Email: mckolani@pitt.edu 
 
10.2 
Collection and Handling Procedures 
 
 
10.2.1 Specimen Kits and Shipping Instructions 
 
Research blood kits will be provided by BAP Kit Building (Biospecimen Accessioning and Processing Core 
Facility).  Collection, handling, and shipping instructions will be included with each kit.  Participating Sites 
may obtain research blood kits by faxing the Supply Order Form to the number provided (found in the 
Forms Packet).  At least two weeks should be allowed to receive the shipping kits.  Kits will be sent via 
FedEx® Ground at no additional cost to the participating institutions.  They will not be forwarded by 
FedEx® rush delivery service unless the participating institution provides their own FedEx® account 
number.  CPN will not cover the cost for rush delivery of kits. 
 
Because charges are incurred for all outgoing kits, a small, but sufficient, supply of specimen collection 
kits should be ordered prior to participant entry. 
• 
ALL sections of the requisition form and specimen collection labels must be completed and legible.  
• 
Blood specimens should be sent over night via FedEx® on cold packs Monday - Thursday ONLY.  
• 
All samples must be shipped to the address provided on the specimen shippers (See Section 10.2.2). 
 
All samples will be shipped in compliance with the International Air Transport Association (IATA) 
Dangerous Goods Regulations. 
 
10.2.2    Research Blood Specimens  
 
Research blood specimens will be collected according to the table in Section 7.1.  Blood specimens for 
the immune assays must be collected M-Th only and shipped overnight for next day analysis.  Detailed 
instructions for collecting, processing, labeling, and shipping the specimens can be found in the 
instructions provided in each blood specimen kit. 
 
Immune Assays:  Heparinized whole blood (4 green-topped tubes) collected at all locations will be 
shipped to the University Of Pittsburgh School Of Medicine.  Trained laboratory personnel will receive 

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and record the specimens, and will also be responsible for processing the blood into plasma and PBMCs.  
PBMCs will be frozen at -70 to -80oC in human serum with 20% DMSO and plasma will be frozen at -
20oC.  Lab personnel will run ELISA assays for anti-MUC1 IgG and FACS analysis of % MDSC.  
Approximately 50% of plasma and 25% of the live cells will be shipped to the Biorepository at the Mayo 
Clinic for storage and later release when requested for analyses of MUC1 immune response (T-cells +/- 
cytokine responses), as well as additional biomarker studies.  
 
Blood specimens for immune assays will be sent to: 
Jia Xue, E1000-17B Biomedical Science Tower 
200 Lothrop Street, Pittsburgh, PA. 15261 
Phone:  412-648-8561 or 412-648-9817; Fax:  412-383-8098; Email: jix11@pitt.edu 
 
For tracking purposes, participating organizations will telephone or email Jia Xue to inform the lab 
that specimens are being sent to the University of Pittsburgh. 
 
Jia Xue,  
 
Email: jix11@pitt.edu 
 
 
 
Mandatory blood specimen for secondary and exploratory endpoints, as well as optional research blood 
collection (for individuals who consent to providing blood for future unspecified research) will take place 
at Baseline/Screening and at Week 24.  See the table on the following page for details. 
 
BAP kits will be available for this blood collection utilizing the MAY2016-08-01 BAP Kit Supply Order 
Form.  If are questions or problems with the BAP kits, please email:  mccc/ncctg@mayo.edu  
 
 
 

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At study completion, remaining frozen biologic specimens will be labeled (study number, participant ID 
number, specimen type, specimen number, date of collection) batched, and shipped (overnight, M-Th 
only) for short-term storage to: 
Biospecimens Accessioning and Processing (BAP) Freezer 
ST SL-39, 150 Third Street Southwest, Rochester, MN  55902 
NCI reserves the option to either retain or relinquish ownership of the unused biologic specimens. If NCI 
retains ownership of specimens, the Contractor shall collect, verify and transfer the requested biologic 
specimens from the site to a NCI-specified repository or laboratory at NCI’s expense.   
 
Biologic specimens collected during the conduct of each clinical trial that are not used during the course 
of the study will be considered deliverables under the contract and thus the property of the NCI. At 
study completion, NCI reserves the option to either retain or relinquish ownership of the unused 
biologic specimens. If NCI retains ownership of specimens, the Contractor shall collect, verify and 
transfer the requested biologic specimens from the site to a NCI-specified repository or laboratory at 
NCI’s expense.  
 
11. 
REPORTING ADVERSE EVENTS  
 
DEFINITION: AE means any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign), 
symptom, or disease temporally associated with participation in a study, whether or not related to that 
participation. This includes all deaths that occur while a participant is on a study. 
 
Please note that all abnormal clinical laboratory values that are determined to be of clinical significance 
based on a physician’s assessment are to be reported as AEs. Those labs determined to be of no clinical 
significance or of unknown clinical significance (per the physician’s assessment) should not be reported 
as AEs. Any lab value of unknown clinical significance should continue to be investigated/followed-up 
further for a final determination, if possible. 
 
Since there is considerable physiologic variability in the Pulmonary Function Tests (PFTs) done at two 
different time points, to report statistically and clinically relevant AEs related to PFTs done at week 24 
the following definitions will be used: 
 
A. For a participant with normal PFTs at baseline (normal PFTs as defined by FEV1 >80% predicted and 
FEV1/FVC ratio ≥ 0.7) 
*Any decline in FEV1 done after vaccination series of ≥ (equal or higher) 12% and ≥ (equal or higher) 
200cc as compared to baseline FEV1 would be reportable regardless of its relatedness to the study 
vaccine. 
 
B. For a participant with abnormal PFTs known previously or determined at the time of baseline 
testing (abnormal PFTs as defined by FEV1 ≤ (equal or less) 80% and FEV1/FVC ratio ˂ 0.7)  
*Any decline in FV1 done after vaccination series of ≥ (equal or higher) 20% and ≥ (equal or higher) 
330cc as compared to baseline FEV1 would be reportable regardless of its relatedness to the study 
vaccine. 
 

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• Death 
• A life-threatening AE 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to perform normal 
life functions 
• A congenital anomaly or birth defect 
• Important medical events that may not be immediately life-threatening or result in 
death or hospitalization should also be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the patient and may require 
intervention to prevent one of the other outcomes. 
 
11.2.2 Reporting SAEs to DCP 
 
11.2.2.1 The Lead Organization and all Participating Organizations will report SAEs on the DCP SAE 
Report Form or application found at http://prevention.cancer.gov/clinical-trials/clinical-trials-
management/protocol-information-office/pio-instructions-and-tools/2012-consortia. 
 
11.2.2.2 Contact the DCP Medical Monitor by email (preferable) or phone within 24 hours of knowledge 
of the event.  
 
Malgorzata (Margaret) Wojtowicz, M.D. 
National Institutes of Health, National Cancer Institute, Division of Cancer Prevention 
Medical and Scientific Monitor 
Lung and Upper Aerodigestive Cancer Research Group 
9609 Medical Center Drive, Rm 5E-104, MSC9781 
Bethesda, MD 20892 (For FedEx, use Rockville, MD  20850) 
Phone:  240-276-7012   
Fax:  240-276-7848 
Email: wojtowim@mail.nih.gov 
 
Include the following information when calling the Medical Monitor: 
• 
Date and time of the SAE 
• 
Date and time of the SAE report 
• 
Name of reporter 
• 
Call back phone number 
• 
Affiliation/Institution conducting the study 
• 
DCP protocol number 
• 
Title of protocol 
• 
Description of the SAE, including attribution to drug 
 
Guidance for the process of coding the SAE can be obtained by contacting the NCI MD Help Desk:  
adeersmd@tech-res.com 
 
11.2.2.3 The Lead Organization and all Participating Organizations will also submit typed SAE reports 
and follow up reports within 48 hours of learning of the event using the DCP SAE Report Form to all of 
the following: 

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• 
Margaret Wojtowicz, M.D., DCP Medical Monitor 
Phone: 240-276-7012 
Email:  wojtowim@mail.nih.gov 
• 
Arjun Pennathur, M.D. Principal Investigator/Study Chair 
Phone: 412-648-6271 
Email:  pennathura@pitt.edu 
• 
CPN Operations Office 
Phone:  507-284-2180 
Email: cancerpreventionnetwork@mayo.edu 
• 
DCP’s Regulatory Contractor CCS Associates, Inc. 
Phone: 650-691-4400 
Email: safety@ccsainc.com  
 
11.2.2.4 The DCP Medical Monitor and CCSA regulatory and safety staff will determine which SAEs 
require FDA submission as IND safety reports. 
 
11.2.2.5 The Lead Organization and all Participating Organizations will comply with applicable regulatory 
requirements related to reporting SAEs to the CIRB/IEC.  
 
11.2.3 Follow-up of SAE 
 
Site staff should send follow-up reports as requested when additional information is available. 
Additional information should be entered on the DCP SAE Report Form in the appropriate format. 
Follow-up information should be sent to all of the above, including DCP, as soon as available.  All SAEs 
will be followed according to institutional standards of good clinical practice.  
 
12. 
STUDY MONITORING 
 
12.1 
Data Management 
 
The Mayo Clinic Cancer Center database will be the database of record for the protocol and subject to 
NCI and FDA audit.  Minimum Data Sets will be submitted to DCP per contract requirements.  Please see 
the DCP-approved CPN Master Data Management Plan. 
 
12.2 
Case Report Forms 
 
Participant data will be collected using protocol-specific case report forms (CRF) utilizing NCI-approved 
Common Data Elements (CDEs). The approved CRFs will be used to create the electronic CRF (e-CRF) 
screens for data entry into the Mayo Clinic Cancer Center database. Amended CRFs will be submitted to 
the DCP Protocol Information Office for review and approval. 
 
12.3 
Source Documents 
 
A source document is any document, form, or record where specific participants’ data are first recorded.  
FDA [21 CFR 312.62 (b)] requires that the investigator “...prepare and maintain accurate case histories 
designed to record all observations and other data pertinent to the investigation on each individual 
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items, source documents include:  
• 
Inpatient and outpatient medical records  
• 
Progress notes  
• 
Consults  
• 
Nursing notes  
• 
Pathology reports  
• 
Radiology reports  
• 
Medicine/radiation administration records  
• 
Surgical reports  
• 
Laboratory reports  
• 
Admission forms  
• 
Flow sheets that are signed and dated  
• 
Protocol or study road maps  
• 
Appointment books  
• 
Participant diaries/calendars 
• 
Participant-completed symptom diary/report card 
 
12.4 
Data and Safety Monitoring Plan 
 
The DCP-approved Master DSMP, applicable to all studies within the CPN Consortium provides detailed 
information regarding data and safety monitoring for this study.  The trial will be monitored closely for 
occurrence of adverse events by the study team and by the Mayo Clinic Cancer Center Data Safety 
Monitoring Board (DSMB).  The DSMB will be consulted regarding whether or not accrual should be 
suspended to allow for investigation in the occurrence of severe adverse events, particularly for those 
that are possibly, probably, or definitely related to the study agent. 
 
12.5 
Sponsor or FDA Monitoring 
 
The NCI, DCP (or their designee), pharmaceutical collaborator (or their designee), or FDA may 
monitor/audit various aspects of the study. These monitors will be given access to facilities, databases, 
supplies and records to review and verify data pertinent to the study.  
 
12.6 
Record Retention 
 
Clinical records for all participants, including CRFs, all source documentation (containing evidence to 
study eligibility, history and physical findings, laboratory data, results of consultations, etc.), as well as 
CIRB records and other regulatory documentation will be retained by the Investigator in a secure 
storage facility in compliance with Health Insurance Portability and Accountability Act (HIPAA), Office of 
Human Research Protections (OHRP), Food and Drug Administration (FDA) regulations and guidances, 
and NCI/DCP requirements, unless the standard at the site is more stringent. The records for all studies 
performed under an IND will be maintained, at a minimum, for two years after the approval of a New 
Drug Application (NDA). For NCI/DCP, records will be retained for at least three years after the 
completion of the research. NCI will be notified prior to the planned destruction of any materials. The 
records should be accessible for inspection and copying by authorized persons of the Food and Drug 
Administration. If the study is done outside of the United States, applicable regulatory requirements for 
the specific country participating in the study also apply. 

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Safety primary endpoint:  AEs and toxicities will be closely monitored for up to 24 weeks after 
participants receive the first dose of the MUC1 vaccine.  All registered and treated participants will be 
evaluable for adverse events (AEs) from the time of their first dose of the vaccine.  To evaluate the AE 
profile for this treatment, the maximum grade for each type of adverse event will be recorded for each 
participant and frequency tables will be reviewed to determine the overall patterns. In addition, the 
number and severity of adverse events will be tabulated and summarized across all grades.  Grade 2+ 
adverse events will be similarly described and summarized separately.  As per NCI CTC Version 4.0, 
toxicities are defined as adverse events that are classified as either possibly, probably, or definitely 
related to the interventional agent.  Overall toxicity incidence, as well as toxicity profiles will be explored 
and summarized. Frequency distributions, graphical techniques, and other descriptive measures will 
form the basis of these analyses. In addition, we will review all adverse event data that are graded as 3, 
4, or 5 and classified as either “unrelated or unlikely to be related” to the study intervention in the event 
of an actual relationship developing.   
 
13.5 
Secondary Objectives, Endpoints, Analysis Plans 
 
• 
To explore potential differences, if any, in the immunogenicity of the vaccine (as assessed at 
weeks 12 and 24 by the IgG anti-MUC1 antibody titer ratio) in current vs. former smokers. We 
will thus continuously monitor enrollment to the trial by smoking status.  Once 15 participants 
are enrolled, a breakdown of enrollment by smoking status will be shared with the study team.  
Based on the smoking status distribution, the study team will make a decision to either continue 
the study as is, or restrict enrollment to either the current or the former smokers in order to 
have at least 15 participants each within the former and current smoker categories.   
• 
To evaluate pre-vaccination levels versus post-vaccination (Week 12) levels of circulating 
myeloid derived suppressor cells (MDSC) and correlate with the ability to respond to the 
vaccine.   For this analysis, we will summarize the data using descriptive statistics and graphical 
methods (i.e. boxplots, scatter plots, etc.).  For continuous MDSC data vs. response data, we will 
use t-tests or Wilcoxon Rank-Sum tests (for non-normal data).  For the associations of 2 
continuous variables, we will use linear regression, the correlation coefficient, and scatter plots.   
 
In addition, as exploratory endpoints we will also assess: 
• 
The relationship between COPD status at pre-registration and immune response in current 
versus former smokers.  In individuals with COPD, the severity of airflow obstruction will be 
measured by the pulmonary function tests as per the GOLD classification   
• 
Whether or not changes in immunogenicity in individuals with COPD corresponds to different 
circulating MDSC levels    
• 
The impact of the MUC1/Poly-ICLC vaccine on inflammation-related high sensitivity C-reactive 
protein (hsCRP) and interleukin-6 (IL-6) 
• 
The ability to successfully vaccinate with MUC1/Poly-ICLC vaccine depending on baseline hsCRP 
and IL-6 levels.   
 
13.6 
Reporting and Exclusions 
 
All registered participants who start treatment and complete both the baseline and 12-week post-
baseline evaluation will be evaluable for the 12-week immunogenicity response primary endpoint using 
the modified intent-to-treat principle, as long as they received the Week 0, Week 2, and Week 10 

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injections (See Section 5.6 for delays in vaccine administration that are considered allowable and will 
not impact evaluability for the primary endpoint).  We plan to over-accrue by about 20% overall to 
ensure an adequate sample size in the primary analysis cohort.  There will be no imputation for missing 
data.  A summary and listing of all major protocol violations will be provided.  All details will be given in 
the final study report and/or manuscript.  Participants lost to follow-up will be censored on the last date 
of assessment (or contact) and as appropriate for analyses that are dependent upon length of study 
participation.  All eligible participants who start treatment will be evaluable for the safety  
 
13.7 Adverse Event Stopping Rule 
 
The trial will be monitored closely for occurrence of adverse events by the study team and by the Mayo 
Clinic Cancer Center Data Safety and Monitoring Board (DSMB) using the adverse event (AE) stopping 
rule specified below: 
 
Adverse Event Stopping Rule: The stopping rule specified below is based on the knowledge available at 
study development. We note that the Adverse Event Stopping Rule may be adjusted in the event of 
either (1) the study re-opening to accrual after any temporary suspension or (2) at any time during the 
conduct of the trial and in consideration of newly acquired information regarding the adverse event 
profile of the treatment(s) under investigation. The study team in consultation with the Mayo DSMB 
may also choose to suspend accrual because of unexpected adverse event profiles that have not crossed 
the specified rule below. 
 
Accrual will be temporarily suspended to this study if at any time we observe events considered at least 
possibly related to study treatment (i.e., an adverse event with attribute specified as "possible", 
"probable", or "definite") that satisfy any of the following criteria for each arm separately: 
 
• If at any time 2 of the initial 10 treated participants or 20% of all participants (i.e. when 
accrual is greater than 10 participants) have experienced a grade 3 or higher adverse 
event.) 
• Each grade 5 event will be reviewed on a case by case basis in a real time fashion to 
determine whether study accrual should be suspended. We will also review all grade 4 
adverse events regardless of attribution to monitor the emergence of any previously 
unrecognized treatment related adverse event. 
 
13.8 
Evaluation of Response 
 
All registered participants who start treatment and complete both the baseline and 12-week post-
baseline evaluation will be evaluable for the 12-week immunogenicity response primary endpoint using 
the modified intent-to-treat principle, as long as they received the Week 0, Week 2, and Week 10 
injections.  All conclusions regarding efficacy will be based on all participants who completed both week 
0 and week 12 and have immunogenicity response values from those time points as well.  Participants 
with undetectable titers at baseline will be included in evaluation and their positive response to the 
vaccine will be defined as an increase in titer to at least two times the lower limit of detection of the 
assay.  
 
 Subanalyses may be performed on the subsets of participants, excluding those for whom major 
protocol deviations have been identified (e.g., early death due to other reasons, early discontinuation of 

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intervention, major protocol violations, etc.). However, sub-analyses may not serve as the basis for 
drawing conclusions concerning efficacy, and the reasons for excluding participants from the analysis 
should be clearly reported. For all measurements of response (i.e. the primary endpoint), the 95% 
confidence intervals will also be provided. 
 
13.9 
Interim Analysis 
 
There are no formal interim efficacy/futility analyses planned for the immune response endpoint.   
 
13.10 Ancillary Studies 
 
Laboratory measures will be correlated with participant outcome (i.e., adverse events, immunogenicity 
response, COPD status, smoking status, etc.) and with each other as well. Cut-points will be determined 
based on previously defined and accepted standards. Descriptive statistics and simple scatter plots will 
be generated to review the continuous biomarker data.  In addition, for continuous biomarker values, 
the actual and % change in the level of each of the biomarkers from baseline to post-baseline time 
points will be explored.  All categorical variables will be analyzed using chi-square tests or Fisher’s exact 
test.  For all translational endpoints, any notable statistical result will be viewed as an impetus for 
further study rather than as a definitive finding in and of itself. 
 
14. 
ETHICAL AND REGULATORY CONSIDERATIONS 
 
14.1 
Form FDA 1572 
 
Prior to initiating this study, the Protocol Lead Investigator at the Lead or Participating Organization(s) 
will provide a signed Form FDA 1572 stating that the study will be conducted in compliance with 
regulations for clinical investigations and listing the investigators, at each site that will participate in the 
protocol. All personnel directly involved in the performance of procedures required by the protocol and 
the collection of data should be listed on Form FDA 1572. 
 
14.2 
Other Required Documents 
 
14.2.1 Current (within two years) CV or biosketch for all study personnel listed on the Form FDA 1572 
and Delegation of Tasks form for the Lead Organization and all Participating Organizations  
 
14.2.2 Current medical licenses (where applicable) for all study personnel listed on Form FDA 1572 and 
Delegation of Tasks form for the Lead Organization and all Participating Organizations 
 
14.2.3 Lab certification (e.g., CLIA, CAP) and lab normal ranges for all labs listed on Form FDA 1572 for 
the Lead Organization and all Participating Organizations 
 
14.2.4 Documentation of training in “Good Clinical Practice” for all study personnel listed on the FDA 
Form 1572 and documentation of training in “Human Research Subjects Protection” for all study 
personnel listed on the Delegation of Tasks form for the Lead Organization and all Participating 
Organizations 
 

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14.2.5 Documentation of Federalwide Assurance (FWA) number for the Lead Organization and all 
Participating Organizations 
 
14.2.6 Signed Investigator’s Brochure/Package Insert acknowledgement form 
 
14.2.7 Delegation of Tasks form for the Lead Organization and all Participating Organizations signed by 
the Principal Investigator for each site and initialed by all study personnel listed on the form 
 
14.2.8   Signed and dated NCI, DCP Financial Disclosure Form for all study personnel listed on Form FDA 
1572 for the Lead Organization and all Participating Organizations 
 
14.3 
Central Institutional Review Board (CIRB) Approval 
 
Prior to initiating the study and receiving agent, the Investigators at the Lead Organization and the 
Participating Organization(s) must obtain written approval to conduct the study from the appropriate 
CIRB. Should changes to the study become necessary, protocol amendments will be submitted to the 
DCP PIO according to DCP Amendment Guidelines. The DCP-approved amended protocol must be 
approved by the CIRB prior to implementation 
 
14.4 
Informed Consent 
 
All potential study participants will be given a copy of the CIRB-approved Informed Consent to review. 
The investigator will explain all aspects of the study in lay language and answer all questions regarding 
the study. If the participant decides to participate in the study, he/she will be asked to sign and date the 
Informed Consent document. The study agent(s) will not be released to a participant who has not signed 
the Informed Consent document. Participants who refuse to participate or who withdraw from the 
study will be treated without prejudice. 
 
Participants must be provided the option to allow the use of blood samples, other body fluids, and 
tissues obtained during testing, operative procedures, or other standard medical practices for further 
research purposes. If applicable, statement of this option may be included within the informed consent 
document or may be provided as an addendum to the consent. A Model Consent Form for Use of Tissue 
for Research is available through a link in the DCP website. 
 
Prior to study initiation, the informed consent document must be reviewed and approved by NCI, DCP, 
the Consortium Lead Organization, and the CIRB for each Organization at which the protocol will be 
implemented. Any subsequent changes to the informed consent must be approved by NCI, DCP, and the 
CIRB prior to initiation. 
 
14.5 
Submission of Regulatory Documents 
 
All regulatory documents are collected by the Consortia Lead Organization and reviewed for 
completeness and accuracy. Once the Consortia Lead Organization has received complete and accurate 
documents from a participating organization, the Consortium Lead Organization will forward the 
regulatory documents to DCP’s Regulatory Contractor: 
 
 
Paper Document/CD-ROM Submissions: 

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Regulatory Affairs Department, CCS Associates, Inc. 
 
2001 Gateway Place, Suite 350 West 
 
San Jose, CA 95110 
 
Phone: 650-691-4400 
 
Fax: 650-691-4410 
 
 
E-mail Submissions: regulatory@ccsainc.com 
 
Regulatory documents that do not require an original signature may be sent electronically to the 
Consortium Lead Organization for review, which will then be electronically forwarded to DCP’s 
Regulatory Contractor. 
 
14.6 
Other 
 
This trial will be conducted in compliance with the protocol, Good Clinical Practice (GCP), and the 
applicable regulatory requirements. 
 
15. 
FINANCING, EXPENSES, AND/OR INSURANCE 
 
No expenses solely associated with this clinical trial will be incurred by the study participant and/or their 
insurance carrier.  However, participants and/or their insurance carriers will be billed for tests and 
procedures that are considered standard-of-care.  In the event of an injury or illness, the study 
participant and/or their insurance carrier will be responsible for all expenses related to the injury or 
illness.  Participants will be provided with payments of up to a total of $270 to cover expenses related to 
their participation in the study. 
 
 
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Y, Kaga K, Miyagi Y, Yokose T, Takano A, Daigo Y, Seino KI. Chemotherapy-Induced IL34 Enhances 
Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of 
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Finn OJ. Vaccines for cancer prevention: a practical and feasible approach to the cancer 
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AK. Mucins in lung cancer: diagnostic, prognostic, and therapeutic implications. Journal of 
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Stricker BH. C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: 
the Rotterdam Study. Journal of clinical oncology : official journal of the American Society of 
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40. 
Martins KA, Bavari S, Salazar AM. Vaccine adjuvant uses of poly-IC and derivatives. Expert review 
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surgical research 1996;63:298-304. 
 
 
 
 

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Consent Form 
 
Study Title for Study Participants: MUC1 Vaccine to Reduce Risk for Lung Cancer 
 
Official Study Title for Internet Search on http://www.ClinicalTrials.gov:  A Pilot 
Study of MUC1 Vaccine in Current and Former Smokers at High Risk for Lung 
Cancer 
  
Introduction  
 
This is a clinical trial, a type of research study. Your study doctor will explain the clinical trial to 
you. Clinical trials include only people who choose to take part in the research. Please take your 
time to make your decision about volunteering. You may discuss your decision with your friends 
and family. You can also discuss this study with your health care team. If you have any 
questions, you can ask your study doctor for more of an explanation. You should only agree to 
participate in this study when you are comfortable enough with the information so that you can 
make an informed decision about joining. 
 
What is the usual approach to my risk for lung cancer?   
 
You are being asked to take part in this study because you are a smoker or former smoker at 
increased risk for lung cancer.  People who are at increased risk and choose not to participate in 
a study are usually followed closely by their doctor to watch for the development of cancer.   
 
What are my other choices if I do not take part in this study?  
 
If you decide not to take part in this study, you have other choices. For example: 
• you may choose to have the usual approach described above, 
• you may choose to take part in a different study, if one is available,  
• or you may choose to do nothing. 
 
 
Why is this study being done? 
 
MUC1 is a natural protein that is changed when a normal cell becomes a cancer cell. The body’s 
immune system can recognize these changes very early in the process of changing from a 
normal cell to a cancer cell.  A vaccine has been developed that consists of a MUC1 protein and 

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another compound, Poly-ICLC.  The Poly-ICLC is believed to make the vaccine more 
effective.  Our goal is to slow or stop the changes from normal to pre-cancer to cancer.  
 
This vaccine has proven to be safe in previous clinical trials in individuals at risk for colon 
cancer.  It also seems to stimulate the body’s immune system. The MUC1/Poly-ICLC vaccine is 
now being tested in persons at high risk for lung cancer due to their smoking history.  
 
The purpose of this study is to test the safety of the vaccine, and to find out what effects, if any, 
it has on stimulating the body’s immune system.  There will be about 50 people taking part in 
this study.  
 
How long will I be in this study?  
 
You will receive 3 doses of the study vaccine over the course of 10 weeks.   The vaccine will be 
given to you in an injection by trained personnel after review of all of your medical history and 
lab tests.  You will receive 0.30 cc (1/20 of a teaspoon) of MUC1/poly-ICLC study vaccine. The 
injection will be administered under the skin in the upper arm (or upper thigh, if needed) with a 
thin, tiny needle (like the one used for a tuberculosis test).  The site of injection will remain the 
same for all injections.  You will remain at the study visit for about 30 minutes after each 
injection to watch for side effects. 
 
You will then be watched for a response to the vaccine and any possible side effects for an 
additional 14 weeks.  Even if you do not finish the study, your doctor will continue to watch you 
for side effects and follow your condition for a total of 24 weeks. 
 
What extra tests and procedures will I have if I take part in this study? 
 
Before you begin the study, you will need to have the following extra tests and procedures to 
find out if you can be in the study:  
• 
Physical exam with review of vital signs (heart rate, temperature, height, weight, 
and blood pressure 
• 
Review of your medical and surgical history 
• 
Assessment of your use of alcohol and tobacco 
• 
Review of any medications you are taking 
• 
Review of your CT scan done within the previous 6 months (to make sure you do not 
have cancer) 
• 
Blood tests, which will require about 3 Tablespoons of blood  
• 
Urine test to evaluate your exposure to tobacco 
• 
Lung function tests 
• 
Pregnancy test, if you are a woman capable of becoming pregnant 
 
Pulmonary Function Tests (PFTs): You will undergo a group of tests called pulmonary function 

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tests (also called lung function tests) to check how well your lungs work. The tests determine 
how much air your lungs can hold, how quickly you can move air in and out of your lungs, and 
how well your lungs put oxygen into and remove carbon dioxide out of your blood. If there are 
any results that are troublesome, you will be informed and asked if you would like to be 
referred to an appropriate health care provider for follow-up.  The types of PFTs you will 
undergo in this study are:  
 
Spirometry: You will breathe into a mouthpiece attached to a recording device 
(spirometer). Spirometry measures how much and how quickly you can move air out of 
your lungs.  
 
Lung Diffusion Testing: You will breathe in air containing a very small amount of carbon 
monoxide and then hold your breath for 10 seconds. You will then rapidly blow it out. 
The exhaled (blown out) gas is tested to determine how much of the carbon monoxide 
was absorbed during the breath and this relates to how well your lungs exchange 
oxygen and carbon dioxide. 
 
As part of this study you will also be asked to answer questions about your tobacco and alcohol 
use, both before you begin the study and again at about Week 24. Researchers want to see if 
tobacco and alcohol use affects the side effects people might get while on this study, or if 
tobacco and alcohol use modifies the effects of the study agents. 
 
If you agree, an optional blood sample (about 2 Tablespoons) will be collected for possible 
future research.  This is described in more detail in the section entitled “Optional Sample 
Collections for Laboratory Studies and/or Biobanking for Possible Future Studies” later in this 
document. 
 
If the exams, tests, and procedures show that you can take part in the study, and you choose 
to, then you will be scheduled to have your first vaccine injection.  A repeat pregnancy test will 
be performed before the vaccination, if applicable. 
 
During the study: 
• Repeat vaccinations at Week 2 and Week 10 
• Repeat blood testing at Weeks 2, 4, 10, 12, and 24 to check your response to the 
vaccine and check for any possible side effects.  This will require about 3 
Tablespoons of blood. 
• Repeat urine testing at Weeks 12 and 24 
• Phone calls at Weeks 16 and 20, and possibly 28 to see how you are doing, ask about 
any side effects, and ask about any new medications you are taking 
• Return visit at Week 24 for a repeat physical exam, repeat blood, urine, and lung 
tests, review of side effects and medications, alcohol and tobacco use follow-up 
assessments, and completion of the Was It Worth It questionnaire which asks a few 
questions about your experience on this clinical trial. 

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someone.  Check with your study doctor about what kind of birth control methods to use and 
how long to use them.  For more information about risks and side effects, ask your study 
doctor.  Should a woman become pregnant or suspect she is pregnant while participating in this 
study, she should inform her study physician immediately. 
 
Effects of other drugs you may be taking 
 
It is important to tell the doctor or study staff if you are taking any prescription medications 
including prescription steroids, over the counter drugs, or herbal supplements.  We will need 
this information to make sure that there is no interaction with the study agent.   
 
Are there benefits to taking part in the study? 
 
This study may or may not help you because we do not know how the study drugs will compare 
to the usual approach for your condition. This study may help us learn things that could help 
people in the future. 
 
Can I stop taking part in this study? 
 
Yes. You can decide to stop at any time. If you decide to stop for any reason, it is important to 
let the study doctor know as soon as possible so you can stop safely. If you stop, you can decide 
whether or not to let the study doctor continue to provide your medical information to the 
organization running the study.  The study doctor will tell you about any new information or 
changes in the study that could affect your health or your willingness to continue in the study. 
 
For the tobacco and alcohol use questions, you can decide to not answer some or all of the 
questions. Your decision will not affect whether you can participate in the study, and it will not 
affect your relationship with your doctor or the study staff. 
 
The study doctor may take you out of the study: 
• If your health changes.  
• If the study is no longer in your best interest. 
• If new information becomes available. 
• If you do not follow the study rules. 
• If the study is stopped early for any reason by the sponsor (National Cancer Institute, 
Division of Cancer Prevention [DCP]), the Central Institutional Review Board (CIRB), or 
the United States Food and Drug Administration (FDA). 
 
What are my rights in this study? 
 
Taking part in this study is your choice. No matter what decision you make, and even if your 
decision changes, there will be no penalty to you. You will not lose medical care or any legal 

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rights. 
 
For questions about your rights while in this study, call the Central Institutional Review Board 
(CIRB) at 888-657-3711.  
 
What are the costs of taking part in this study?  
 
The MUC1 vaccine will be supplied at no charge while you take part in this study. The cost of 
study-specific exams, tests, and any other procedures will be paid for by the study.  Some costs 
associated with your care may be considered standard of care, and will be billed to you or your 
insurance company. You will have to pay for any costs (including deductibles and co-payments) 
not covered by your health insurer. 
 
The study will pay for the following: 
• MUC1 vaccine 
• Physical exams and assessments 
• Blood tests 
• Urine tests to evaluate your exposure to tobacco 
• Lung function tests 
• Blood collection for optional research 
• Pregnancy tests, if applicable 
• Questionnaires and Vaccine Report Cards 
• Phone calls to check on side effects and symptoms 
 
You or your insurance company will pay for the following: 
• CT scan that is reviewed to confirm the fact that there is no cancer.  This will have been 
completed at a time point that is the same as your usual and routine clinical care 
 
Before you decide to be in the study, you should check with your health plan or insurance 
company to find out exactly what they will pay for.  
 
Will I be paid for participating in the study? 
 
If you complete the study, you will receive $270 to cover the costs associated with participation 
in the study, such as parking, transportation, and child care. This will be paid as follows: $50.00 
for completing the screening visit, $50.00 for each vaccine injection, and $70.00 for completion 
of the post-intervention visit. 
 
The payments will be authorized at the end of each visit, but it will take some time to process 
the payment and provide the payment to you. 
 
What happens if I am injured or hurt because I took part in this study?  

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If you feel you have been injured or hurt as a result of taking part in the study, it is important 
that you tell the study doctor immediately. You will get medical treatment if you are injured or 
hurt as a result of taking part in this study.  
 
The study sponsors will not offer to pay for medical treatment for injury. Your insurance 
company may not be willing to pay for study-related injury. If you have no insurance coverage, 
you would be responsible for any costs. Even though you are in a study, you keep all of your 
legal rights to receive payment for injury caused by medical errors. 
 
Who will see my medical information?  
 
Your privacy is very important to us.  The study doctors will make every effort to protect it.  The 
study doctors have a privacy permit to help protect your records if there is a court case.  
However, some of your medical information may be given out if required by law.  If this should 
happen, the study doctors will do their best to make sure that any information that goes out to 
others will not identify who you are.  
 
Some of your health information, such as your response to cancer treatment, results of study 
tests, and medicines you took, will be kept by the study sponsor in a central research database.  
However, your name and contact information will not be put in the database.  If information 
from this study is published or presented at scientific meetings, your name and other personal 
information will not be used.  
 
There are organizations that may look at your study records.  Your health information in the 
research database also may be shared with these organizations.  They must keep your 
information private, unless required by law to give it to another group.   
 
Some of these organizations are: 
• 
The study sponsor, NCI Division of Cancer Prevention 
• 
The Central Institutional Review Board, CIRB, is a group of people who review the 
research with the goal of protecting the people who take part in the study. 
• 
The Food and Drug Administration and the National Cancer Institute. 
• 
The National Cancer Institute will obtain information for this clinical trial under data 
collection authority Title 42 U.S.C. 285. 
 
Where can I get more information? 
 
You may visit the NCI website at http://cancer.gov/ for more information about studies or 
general information about cancer. You may also call the NCI Cancer Information Service to get 
the same information at: 1-800-4-CANCER (1-800-422-6237).  
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 

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by U.S. law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 
 
Who can answer my questions about this study? 
 
You can talk to the study doctor about any questions or concerns you have about this study or 
to report side effects or injuries. Contact the study doctor __________________ (insert name of 
study doctor[s]) at __________________ (insert telephone number). 
 
 
 
 
This section is about optional studies you can choose to take part in.  
 
This part of the consent form is about optional studies that you can choose to take part in. You 
will not get health benefits from any of these studies. The researchers leading this optional 
study hope the results will help other people with cancer or at high risk for cancer in the future. 
 
The results will not be added to your medical records, and you or your study doctor may not 
know the results. You will not be billed for these optional studies.  
 
You can still take part in the main study even if you say ‘no’ to any or all of these studies. If you 
sign up for but cannot complete any of the studies for any reason, you can still take part in the 
main study. 
 
As part of the main study, you will be asked to complete the ‘Was It Worth It?’ questionnaire at 
Week 24. Your responses will be reviewed as part of the main study. However, you have the 
option to allow your responses to be included in a central Quality of Life database (along with 
demographic information) that is accessible to non-study investigators. If you do not wish to 
include your responses in the central Quality of Life database, your responses will only be 
reviewed as part of the main study. 
 
 
 
Please circle your answer to show whether or not you would like to take part in this option: 
 
I agree to have my responses to the Was It Worth It? Questionnaire included in a central 
Quality of Life database (along with demographic information) that is accessible to non-study 
investigators. 
 
 
YES 
 
NO 
 

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Optional Sample Collections for Laboratory Studies and/or Biobanking for 
Possible Future Studies 
 
Researchers are trying to learn more about cancer, diabetes, and other health problems. Much 
of this research is done using blood samples from study participants like you. Through these 
studies, researchers hope to find new ways to prevent, detect, treat, or cure health problems.  
 
Some of these studies may be about genes. Genes carry information about features that are 
found in you and in people who are related to you. Researchers are interested in the way that 
genes affect how your body responds to treatment. 
 
If you choose to take part, a sample of your blood will be collected. The researchers ask your 
permission to store and use your samples and health information for medical research.  The 
research that may be done is unknown at this time. Storing samples for future studies is called 
“biobanking.” The Biobank is being run by the Cancer Prevention Network (CPN) at the Mayo 
Clinic and supported by the National Cancer Institute. 
 
WHAT IS INVOLVED?  
 
If you agree to take part, here is what will happen next: 
 
1) An additional 2 Tablespoons of blood will be collected from a vein in your arm. 
2) Your samples and some related information will be stored in the Biobank at the Mayo Clinic 
along with samples from other people who choose to take part.  
3) Your samples will be used for analyses directly related to this study, including additional 
indicators of immune response. 
4) The samples will be stored at the Mayo Clinic until the end of the study, when they may be 
transferred to the National Institutes of Health.  Left-over blood after the main study is 
complete will also be available for future unspecific research, in addition to the optional 
blood draw. 
5) Qualified researchers can submit a request to use the materials stored in the Biobank.  A 
research committee will review each request. There will also be an ethics review to ensure 
that the request is necessary and proper. Researchers will not be given your name or any 
other information that could directly identify you. 
6) Neither you nor your doctor will be notified if/when research is conducted using your 
samples. 
7) Some of your genetic and health information may be placed in the central databases that 
may be public, along with information from many other people.  Information that could 
directly identify you will not be included. 
 
WHAT ARE THE POSSIBLE RISKS?  

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1) The most common risks related to drawing blood from your arm are brief pain and possibly 
a bruise.  
2) There is a risk that someone could get access to the personal information in your medical 
records or other information we have stored about you.  
3) There is a risk that someone could trace the information in a central database back to you. 
Even without your name or other identifiers, your genetic information is unique to you. The 
researchers believe the chance that someone will identify you is very small, but the risk may 
change in the future as people come up with new ways of tracing information.  
 
There are laws against the misuse of genetic information, but they may not give full protection. 
New health information about inherited traits that might affect you or your blood relatives 
could be found during a study. The researchers believe the chance these things will happen is 
very small, but cannot promise that they will not occur.  
 
A new Federal law, called the Genetic Information Nondiscrimination Act (GINA), generally 
makes it illegal for health insurance companies, group health plans, and most employers to 
discriminate against you based on your genetic information. This law generally will protect you 
in the following ways:  
 
• Health insurance companies and group health plans may not request your genetic 
information that we get from this research.  
• Health insurance companies and group health plans may not use your genetic information 
when making decisions regarding your eligibility or premiums.  
 
Employers with 15 or more employees may not use your genetic information that we get from 
this research when making a decision to hire, promote, or fire you or when setting the terms of 
your employment. All health insurance companies and group health plans must follow this law 
by May 21, 2010. All employers with 15 or more employees must follow this law as of 
November 21, 2009. 
 
 
 
Be aware that this new Federal law does not protect you against genetic discrimination by 
companies that sell life insurance, disability insurance, or long-term care insurance.  
 
 
HOW WILL INFORMATION ABOUT ME BE KEPT PRIVATE?  
 
Your privacy is very important to the researchers and they will make every effort to protect it. 
Here are just a few of the steps they will take: 
 
1) When your sample(s) is sent to the researchers, no information identifying you (such as 
your name or social security number) will be sent. Samples will be identified by a unique 
study code only.  

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2) The list that links the unique code to your name will be kept separate from your sample and 
health information. Any Biobank and Mayo Clinic staff with access to the list must sign an 
agreement to keep your identity confidential. 
3) Researchers to whom the Cancer Prevention Network or the National Cancer Institute sends 
your sample and information will not know who you are. They must also sign an agreement 
that they will not try to find out who you are. 
4) Information that identifies you will not be given to anyone, unless required by law. 
5) If research results are published, your name and other personal information will not be 
used. 
 
WHAT ARE THE POSSIBLE BENEFITS?  
 
You will not benefit from taking part.  The researchers, using the samples from you and others, 
might make discoveries that could help people in the future. 
 
ARE THERE ANY COSTS OR PAYMENTS?  
 
There are no costs to you or your insurance. You will not be paid for taking part; however, you 
may receive some funds to defray some of the cost of participating (e.g., parking, child care). If 
any of the research leads to new tests, drugs, or other commercial products, you will not share 
in any profits. 
 
WHAT IF I CHANGE MY MIND?  
 
If you decide you no longer want your samples to be used, you can call the study doctor,  
<name>, at <telephone number> who will let the researchers know. Then, any sample that 
remains in the bank will no longer be used. Samples or related information that have already 
been given to or used by researchers will not be returned. 
 
WHAT IF I HAVE MORE QUESTIONS?  
 
If you have questions about the use of your samples for research, contact the study doctor, 
<name>, at <telephone number> 
 
Please circle your answer to show whether or not you would like to take part in each option. 
 
 
SAMPLES FOR THE OPTIONAL LABORATORY STUDIES: 
 
 
I agree to have my blood samples collected, and I agree that these samples and related 
information may be used for the optional laboratory studies described above. 
 
 
YES 
 
NO 

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I agree that my study doctors, or their representative, may contact me or my physician to see if 
I wish to learn about results from these optional studies. 
 
 
YES 
 
NO 
 
 
SAMPLES AND INFORMATION FOR FUTURE RESEARCH STUDIES: 
 
 
I agree that my blood samples and related information may be collected and kept in a Biobank 
for use in future health research. 
 
 
YES 
 
NO 
 
I agree that the information from my tobacco and alcohol use assessments may be used in 
future health research. 
 
 
YES 
 
NO 
 
I agree that my blood samples and related information may be given to researchers at outside 
institutions 
 
YES 
 
NO 
 
I agree that my study doctors, or their representative, may contact me or my physician to see if 
I wish to participate in other research in the future. 
 
 
YES 
 
NO 
 
This is the end of the section about optional studies. 
 
 
 
 
 
My Signature Agreeing to Take Part in the Main Study 
I have read this consent form or had it read to me. I have discussed it with the study doctor and 
my questions have been answered. I will be given a signed copy of this form. I agree to take 
part in the main study and any additional studies where I circled “yes.”  
 
Participant’s signature ________________________________ 
 

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Date of signature_____________________________________ 
 
 
Signature of person(s) conducting the informed consent discussion ______________________ 
 
Date of signature_________________________________  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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• Lung function tests 
• Review your symptom diary and discuss any side effects, symptoms, 
and medications you are taking 
• Alcohol and tobacco use follow-up assessments 
• Blood and urine tests for safety monitoring and to test the response 
to the vaccine 
• Optional blood collection for research 
• Questionnaire about your experience on this clinical trial: Was It 
Worth It? 
Week 28 
• Phone call to see how you are doing might take place, if needed, to 
ask about side effects and ask about any medications you are taking. 
 

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APPENDIX B 
 
GLOSSARY 
 
aa – Amino acid 
AA – Advanced adenoma 
ADL – Activities of daily living 
AE – Adverse events 
ADCC – antibody-dependent cell-mediated cytotoxicity 
ANA – Antinuclear antibody 
BAP – Biospecimens Accessioning and Processing 
CACC – Colitis-associate colon cancer 
CIRB – Central Institutional Review Board 
CPN – Cancer Prevention Network 
CRF – Case report form 
CTL – Cytotoxic T-lymphocytes 
DCP – NCI, Division of Cancer Prevention 
dsRNA – double-stranded RNA 
FAP – Familial adenomatous polyposis 
FDA – Food and Drug Administration 
HNPCC – Heritable nonpolyposis colorectal cancer 
IBD – Irritable bowel disorder  
IFNs – Interferons  
IgG – Immunoglobulins  
IND – Investigational new drug 
IRB – Institutional Review Board 
MDSC – Myeloid derived suppressor cells 
MUC1 – Mucin 1 (high molecular weight type I transmembrane glycoprotein) 
NCI – National Cancer Institute 
NK – Natural killer cells 
NF-kB – Nuclear factor kappa-light-chain-enhancer of activated B cells 
OAS – Oligoadenylate synthetase  
PBMC – Peripheral blood mononuclear cells 
PO – Participating Organization 
PKR – Protein kinase receptor 
SAE – Serious adverse events 
T12 – Antibody titer at week 12 
Th cells – T-helper cells 
TLR – Toll like receptor 
VNTR – Variable number of tandem repeats 
WIWI – Was It Worth It Questionnaire 
 
 
 
 
 
 

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APPENDIX C 
 
Was It Worth It Questionnaire 
 
Visit type (Time point):* 
 Week 24 or early termination 
 
             ------------------------------------------------------------------ 
Participating in a clinical trial / research study is a personal choice and an individual 
experience.  We would like to get your feedback on your experience in this research study.  
Please respond to the following questions as indicated. 
 
Directions:  Please answer each question by circling Y (for yes), N (for no), or U (for uncertain). 
 
 
Was it worthwhile for you to participate in this research study? 
 
       Y    N 
U 
 
 
If you had to do it over, would you participate in this research study again?     Y    N 
U 
 
 
Would you recommend participating in this research study to others? 
      Y 
   N 
U 
 
 
Directions:  Circle one response 
 
 
Overall, did your quality of life change by participating in this research study? 
 
 
 
It improved 
               It stayed the same 
 
It got worse 
 
 
 
Overall, how was your experience of participating in this research study?  
 
 
 
Better than I expected 
The same as I expected 
Worse than I expected 
 
 
If there was one thing that could have been done to improve your experience in this research 
study, what would it be? 
 
 
 
 
Would you like to talk to someone about your concerns (circle one response)?     Yes   No 
 
_______________________________________   ___________________________________________ 
Signature 
                                                              Date 

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APPENDIX D 
 
Vaccine Report Card 
 
Dear Study Participant, 
 
Thank you for your willingness to participate in this clinical trial of the MUC1 vaccine.  This is 
one of the first cancer prevention vaccine trials, and we want to carefully document the 
vaccine experience. 
 
In this booklet you will find a “vaccine report card” to record symptoms.  Please review these 
instructions carefully.  If you have any questions about the report card, ask your study team.   
 
When to record symptoms:   
The day of your first vaccine injection will be considered Day 0.   
• On Day 2, please record symptoms you have experienced since you left your study visit.  
If you took any medications to relieve symptoms, please write them down.  If the 
symptoms have disappeared, write down the date on the report card in the column 
labeled “date symptoms disappeared.”  Once a symptom disappears, you do not need 
to continue recording anything about that symptom. 
• On Day 7, write down all of the symptoms you experience from Day 3 to Day 7.  
• On Day 14, write down all of the symptoms you experience from Day 8 to Day 14. 
• If you are not scheduled to return for a study visit on or around Day 14, please send this 
booklet back to the study team by mail, fax, or email.  Your study team members will 
provide a postage-paid envelope, fax number, or email address for you. 
 
What to record: 
The previous studies with the MUC1 vaccine have shown us that some, but not all people 
receiving the vaccine will have reactions such as redness at the injection site, swelling, warmth 
or itching, and pain or tenderness. Not everyone experiences these symptoms. Some people 
will have no symptoms.   
 
If there are any other symptoms you experience and want to document, please write them in 
the text box on the back page of this booklet. If assistance is needed to complete the vaccine 
report card, please contact your study team. 
 
 
 
 
 
 
 
 

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Appendix E. Alcohol Assessment: Baseline 
Instructions:  For the following questions about drinking alcoholic beverages, a drink means a 12 oz. beer, a 5 oz. glass of wine, 
or one and a half ounces of liquor. 
1. 
In your entire life, have you had at least 12 drinks of any kind of alcoholic beverage? (check one) 
 Yes 
 No (End) 
 Choose not to answer (End) 
 Don’t know/Not sure 
(If No or Choose not to answer), stop assessment 
 
2. 
In the past 12 months, on average, how often did you drink any type of alcoholic beverage?  (Enter the number of days you 
drank based on the timeframe checked below.  Enter 0 if you never drank and skip to Question 6.) _______ 
(If more than 0, check one) 
 Week  
 Month 
 Year 
 Choose not to answer 
 Don’t know/Not sure 
 
3. 
In the past 12 months, on those days that you drank alcoholic beverages, on average, how many drinks did you have per 
day?  
(Enter the average number of drinks per day)_______ 
(If no answer, check one) 
 Choose not to answer 
 Don’t know/Not sure 
 
4. 
In the past 12 months, on how many days did you have 5 or more drinks of any alcoholic beverage?   
(Enter the number of days you had 5 or more drinks, or enter 0 if none.)________ 
(If no answer, check one) 
 Choose not to answer 
 Don’t know/Not sure 
 
5. 
Was there ever a time or times in your life when you drank 5 or more drinks of any kind of alcoholic beverage almost every 
day?  
       (check one) 
 Yes 
 No  
 Choose not to answer 
 Don’t know/Not sure 
 
6. 
If you do not currently drink alcoholic beverages, but did in the past, how long has it been since you last drank regularly?  
       (check one) 
 Within the past month (0 to 1 month ago) 
 Between 1 and 3 months (1 to 3 months ago) 
 Between 3 and 6 months (3 to 6 months ago) 
 Between 6 and 12 months (6 to 12 months ago) 
 Between 1 and 5 years (1 to 5 years ago) 
 Between 5 and 15 years (5 to 15 years ago) 
 More than 15 years ago  
 Don’t know/Not sure 
 Never drank regularly 
 Choose not to answer 

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Alcohol Assessment: Baseline (continued) 
 
7. 
At the heaviest point, either now or in the past, on the days when you drank, about how many drinks did you drink a day on 
the average?  (Enter the number of drinks a day)________ 
       (If no answer, check one)  
 Choose not to answer 
 Don’t know/Not sure 
 
8. 
How many years have you been drinking (or did drink) regularly?    ______ years 
(If no answer, check one) 
 Choose not to answer 
 Don’t know/Not sure  
 
9. 
At what age did you begin drinking regularly?   ______ years of age 
 
(If no answer, check one) 
 Choose not to answer 
 Don’t know/Not sure  
 
10. What type(s) of alcohol do you drink?  
 
Wine  
(check one) 
Yes     
No    
 Choose not to answer 
Liquor   
(check one) 
Yes     
No    
 Choose not to answer 
Beer   
(check one) 
Yes     
No    
 Choose not to answer 
Wine cooler   
(check one) 
Yes     
No    
 Choose not to answer 
 
 
 
 
 
_____________________________     ___________________ 
Investigator signature  
                Date 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix E. Alcohol Assessment: Follow-Up 
 
 
Instructions:  For the following questions about drinking alcoholic beverages, a drink means a 12 oz. beer, a 5 oz. glass of wine, 
or one and a half ounces of liquor. 
 
 
1. During the past 30 days, did you drink any alcoholic beverages?  (check one) 
 Yes 
 No (End) 
 Choose not to answer (End) 
 Don’t know/Not sure 
    (If No or Choose not to answer, stop assessment) 
 
2. During the past 30 days, how many days per week or per month did you drink any alcoholic beverages, on the average?  
(Enter number of days you drank based on the timeframe checked below.  Enter 0 if you did not drink.) ______ 
(If more than 0), specify (check one) 
 Week  
 Month 
 Choose not to answer 
 Don’t know/Not sure 
 
3. On the days when you drank, on average, about how many drinks did you have?    
(Enter the average number of drinks you had per day. Enter 0 if you did not drink.) _______ 
(If no answer, check one) 
 Choose not to answer 
 Don’t know/Not sure 
 
4. In the past 30 days, on how many days did you have 5 or more drinks per day?  
_____________ (Enter the number of days you had 5 or more drinks, or enter 0 if none.)  
  (If no answer, check one.) 
 
 None 
 
 Choose not to answer  
 
 Do not know/Not sure 
 
 
 
 
 
 
_____________________________     ___________________ 
Investigator signature  
                Date 
 
 
 
 
 

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Appendix E. Tobacco Assessment: Baseline 
 
Section A. Basic Cigarette Use Information 
1. Have you smoked at least 100 cigarettes (5 packs = 100 cigarettes) in your entire life? 
Yes  
 Choose not to answer → Skip to Section B 
 
 No → Skip to Section B 
 Don’t know/Not sure → Skip to Section B 
 
2. How old were you when you first smoked a cigarette (even one or two puffs)?    _______ Years old 
 
(If no answer, check one) 
  
Choose not to answer       
Don’t know/Not sure 
 
3. How old were you when you first began smoking cigarettes regularly?   _______ Years old 
 
   (If no answer, check one) 
     
Refused        
Don’t know/Not sure     
Check here if you have never smoked cigarettes regularly. 
 
4. How many total years have you smoked (or did you smoke) cigarettes? Do not count any time you may have stayed off 
cigarettes.       
  (If you smoked less than one year, write “1.”)  ______ Years 
 
 
Choose not to answer       
Don’t know/Not sure 
 
5. 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 
(If no answer, check one) 
 
Choose not to answer       
Don’t know/Not sure 
 
6. Do you NOW smoke cigarettes? (check one) 
 Everyday 
 Some days 
 Choose not to answer → Skip to question 8 
 Not at all → Skip to question 8 
 
7.  How soon after you wake up do you smoke your first cigarette? (check one) 
  Within 30 minutes            
  After 30 minutes      
 Choose not to answer 
 
8. 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)   (check one) 
Yes     
No 
1-7 days   (check one)   
Yes     
No 
(If yes), Number of days since last cigarette ________ 
Less than 1 month (check one)   
Yes     
No 
(If yes), Number of weeks since last cigarette _________ 
Less than 1 year (check one)   
Yes     
No 
(If yes), Number of months since last cigarette __________ 
More than 1 year (check one)   
Yes     
No 
(If yes), Number of years since last cigarette ___________ 
Don’t know/Don’t remember   (check one)   
Yes     
No 
Choose not to answer 
 
 
 

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Tobacco Assessment: Baseline (continued) 
Section B. Use of Other Forms of Tobacco 
 
9.  Have you ever used other forms of tobacco, not including cigarettes? (check one) 
 Yes    
 Choose not to answer 
 No → Skip to Section C 
 
10.  How often do you/did you use other forms of tobacco? 
Every day   (check one)     
Yes     
No       (If yes), Number of times per day ________ 
Some days   (check one)   
Yes     
No     (If yes), Number of days _______  
(If yes), Per (select one)     
 Week       
 Month    
Year 
 
11. Which of the following products have you ever used regularly?  (Mark yes, no., or choose not to answer for all choices) 
Cigarettes 
(check one)  
Yes     
No    
 Choose not to answer 
Traditional cigars, cigarillos or filtered cigars 
(check one)  
Yes     
No    
 Choose not to answer 
Hookah 
(check one)  
Yes     
No    
 Choose not to answer 
Bidis 
(check one)  
Yes     
No    
 Choose not to answer 
Snus 
(check one)  
Yes     
No    
 Choose not to answer 
E-cigarettes or other electronic nicotine delivery system 
(check one)  
Yes     
No    
 Choose not to answer 
Pipes 
(check one)  
Yes     
No    
 Choose not to answer 
Waterpipe 
(check one)  
Yes     
No    
 Choose not to answer 
Clove cigarettes or kreteks 
(check one)  
Yes     
No    
 Choose not to answer 
Smokeless tobacco (like dip, chew, or snuff) 
(check one)  
Yes     
No    
 Choose not to answer 
Paan with tobacco, gutka, zarda, khaini 
(check one)  
Yes     
No    
 Choose not to answer 
Other, please specify: 
 
 
 
12. If you do not currently use other forms of tobacco, but did in the past, how long has it been since you last used other forms 
of tobacco regularly? (check one) 
 Within the past month (0 to 1 month ago) 
 Between 1 and 5 years (1 to 5 years ago) 
 Between 1 and 3 months (1 to 3 months ago) 
 Between 5 and 15 years (5 to 15 years ago) 
 Between 3 and 6 months (3 to 6 months ago) 
 More than 15 years ago 
 Between 6 and 12 months (6 to 12 months ago) 
 Don’t know/Not sure 
 Never used other forms of tobacco regularly     
 Choose not to answer 
 
Section C. Second-Hand Smoke Exposure 
13. Are you currently living with a smoker?  (check one) 
Yes       
No       
 Choose not to answer 
  
14. In the past 30 days, have you lived in a place where other people smoked cigarettes indoors?  (check one) 
Yes       
No       
 Choose not to answer 
 
15. In the past 30 days, have you worked in a place where other people smoked cigarettes indoors? (check one) 
Yes       
No       
 Choose not to answer 
 
16. Thinking of all your childhood and adult years, have you ever lived in a place where other people smoked cigarettes 
indoors? (check one) 
Yes → In total, for about how many years? _______ If less than 1, write “1.”   
No        
 Choose not to answer 
 
17. Thinking of all the years you have worked, have you ever worked in a place where other people smoked cigarettes indoors?    
(check one) 
Yes → In total, for about how many years? _______ If less than 1, write “1.”   
No        
 Choose not to answer             _____________________________     ___________________ 
Investigator signature  
                Date 

MAY2016-08-01 
Version 5.0, Amendment 6 
January 25, 2021 
DCP Protocol Template Version 8.5 
–82– 
08/31/2016 
Appendix E. Tobacco Assessment: Follow-Up 
 
1. Do you NOW smoke cigarettes? (check one) 
 Everyday 
 Some days 
 Choose not to answer→ Skip to Question 3. 
 Not at all → Skip to Question 3. 
 
2. On average, when you 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 
(If no answer, check one) 
Choose not to answer      
Don’t know/Not sure 
 
3. 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)   (check one)   
Yes     
No 
1-7 days    (check one)   
Yes     
No 
 
(If yes), Number of days since last cigarette _____ 
Less than 1 month   (check one)   
Yes     
No 
 
(If yes), Number of weeks since last cigarette _____ 
Less than 1 year   (check one)   
Yes     
No 
 
(If yes), Number of months since last cigarette _____ 
More than 1 year   (check one)   
Yes     
No 
 
(If yes), Number of years since last cigarette _____ 
Don’t know/Don’t remember   (check one)   
Yes     
No 
Choose not to answer 
 
 
4. Since your last visit, have you used other forms of tobacco, not including cigarettes?  (check one) 
 Yes 
 Choose not to answer (End) 
  No (End)        (If no), stop assessment 
 
5. How often do you/did you use other forms of tobacco?  
Every day    (check one)   
Yes     
No      (If yes), Number of times per day ________ 
Some days   (check one)   
Yes     
No     (If yes), Number of days ________  
 
                                                               (If yes), per (select one)    
Week    
Month    
Year 
     
Choose not to answer 
 
6.   Since your last visit, which of the following products have you used?  (Mark yes or no for all choices) 
Cigarettes 
(check one)  
Yes     
No    
 Choose not to answer 
Traditional cigars, cigarillos or filtered cigars 
(check one)  
Yes     
No    
 Choose not to answer 
Hookah 
(check one)  
Yes     
No    
 Choose not to answer 
Bidis 
(check one)  
Yes     
No    
 Choose not to answer 
Snus 
(check one)  
Yes     
No    
 Choose not to answer 
E-cigarettes or other electronic nicotine delivery system 
(check one)  
Yes     
No    
 Choose not to answer 
Pipes 
(check one)  
Yes     
No    
 Choose not to answer 
Waterpipe 
(check one)  
Yes     
No    
 Choose not to answer 
Clove cigarettes or kreteks 
(check one)  
Yes     
No    
 Choose not to answer 
Smokeless tobacco (like dip, chew, or snuff) 
(check one)  
Yes     
No    
 Choose not to answer 
Paan with tobacco, gutka, zarda, khaini 
(check one)  
Yes     
No    
 Choose not to answer 
Other, please specify: _________________________ 
 

MAY2016-08-01 
Version 5.0, Amendment 6 
January 25, 2021 
DCP Protocol Template Version 8.5 
–83– 
08/31/2016 
Tobacco Assessment: Follow-Up (continued) 
 
7. If you do not currently use other forms of tobacco, but did in the past, how long has it been since you last used other forms of 
tobacco regularly? (check one) 
 Within the past month (0 to 1 month ago) 
 Between 1 and 3 months (1 to 3 months ago) 
 Between 3 and 6 months (3 to 6 months ago) 
 Between 6 and 12 months (6 to 12 months ago) 
 Between 1 and 5 years (1 to 5 years ago) 
 Between 5 and 15 years (5 to 15 years ago) 
 More than 15 years ago 
 Don’t know/Not sure 
 Choose not to answer 
 Never used other forms of tobacco regularly 
 
The following instructions pertain to questions 8 -10.  During each of the following time frames, please indicate whether you 
smoked cigarettes every day, some days, or not at all. 
 
8.  During study treatment (check one) 
 Smoked every day 
 Smoked some days 
 Did not smoke at all 
 Don’t know/not sure 
 Choose not to answer 
 Not applicable  
 
9.  After the end of study treatment (check one)  
 Smoked every day 
 Smoked some days 
 Did not smoke at all 
 Don’t know/not sure 
 Choose not to answer 
 Not applicable (I have not completed the study treatment) 
 
 
 
10.  Since your last visit to this clinic (check one) 
 
 Smoked every day 
 Smoked some days 
 Did not smoke at all 
 Don’t know/not sure 
 Choose not to answer 
 Not applicable (This is my first visit to this clinic) 
 
 
 
 
_____________________________     ___________________ 
Investigator signature  
                Date 
 

MAY2016-08-01 
Version 5.0, Amendment 6 
January 25, 2021 
DCP Protocol Template Version 8.5 
–84– 
08/31/2016 
Appendix F. Alcohol and Tobacco Cessation Resources 
National and local resources to help with alcohol abuse and alcoholism 
NIAAA’s online guide Treatment for Alcohol Problems: Finding and Getting Help is written for 
individuals, and their family and friends, who are looking for options to address alcohol 
problems. It is intended as a resource to understand what treatment choices are available and 
what to consider when selecting among them. 
https://pubs.niaaa.nih.gov/publications/treatment/treatment.htm 
Other resources: 
National Institute on Alcohol Abuse and Alcoholism www.niaaa.nih.gov  
301–443–3860  
National Institute on Drug Abuse www.nida.nih.gov  
301–443–1124  
National Clearinghouse for Alcohol and Drug Information www.samhsa.gov  
1–800–729–6686  
Substance Abuse Treatment Facility Locator www.findtreatment.samhsa.gov  
1–800–662–HELP  
Alcoholics Anonymous (AA) www.aa.org  
212–870–3400 or check your local phone directory under “Alcoholism”  
Moderation Management www.moderation.org 
212–871–0974  
Secular Organizations for Sobriety www.sossobriety.org  
323–666–4295  
SMART Recovery www.smartrecovery.org  
440–951–5357  
Women for Sobriety www.womenforsobriety.org  
215–536–8026  
Al-Anon Family Groups www.al-anon.alateen.org  
1–888–425–2666 for meetings  
Adult Children of Alcoholics www.adultchildren.org 
310–534–1815  

MAY2016-08-01 
Version 5.0, Amendment 6 
January 25, 2021 
DCP Protocol Template Version 8.5 
–85– 
08/31/2016 
National and local resources to help with quitting smoking 
NCI’s Smokefree.gov offers science-driven tools, information, and support that has helped 
smokers quit. You will find state and national resources, free materials, and quitting advice 
from NCI. 
Smokefree.gov was established by the Tobacco Control Research Branch of NCI, a component 
of the National Institutes of Health, in collaboration with the Centers for Disease Control and 
Prevention and other organizations. 
Publications available from the Smokefree.gov Web site include the following: 
• 
Clearing the Air: Quit Smoking Today for smokers interested in quitting. 
• 
Clear Horizons for smokers over age 50. 
• 
Forever Free™  for smokers who have recently quit. 
• 
Forever Free for Baby and Me™, in English and Spanish, for pregnant smokers who have 
recently quit. 
• 
Pathways to Freedom: Winning the Fight Against Tobacco for African American smokers. 
NCI’s Smoking Quitline at 1–877–44U–QUIT (1–877–448–7848) offers a wide range of services, 
including individualized counseling, printed information, referrals to other resources, and 
recorded messages. Smoking cessation counselors are available to answer smoking-related 
questions in English or Spanish, Monday through Friday, 8:00 a.m. to 8:00 p.m., Eastern Time. 
Smoking cessation counselors are also available through LiveHelp, an online instant messaging 
service. LiveHelp is available Monday through Friday, 8:00 a.m. to 11:00 p.m., Eastern Time. 
Your state has a toll-free telephone quitline. Call 1–800–QUIT–NOW (1–800–784–8669) to get 
one-on-one help with quitting, support and coping strategies, and referrals to resources and 
local cessation programs. The toll-free number routes callers to state-run quitlines, which 
provide free cessation assistance and resource information to all tobacco users in the United 
States. This initiative was created by the Department of Health and Human Services. For more 
information about quitlines, speak to an expert on the Smokefree.gov Web site.