Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Vaccine in Patients With Newly Diagnosed Advanced Adenomas
Phase: PHASE2
Conditions: Colorectal Adenoma, Colorectal Adenoma With Severe Dysplasia, Colorectal Carcinoma, Colorectal Tubulovillous Adenoma
Sponsor: National Cancer Institute (NCI)

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DCP Protocol #:  
MAY2013-01-01    
 
Local Protocol #: 
MAY2013-01-01 
 
Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Vaccine in Patients with Newly 
Diagnosed Advanced Adenomas 
 
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 Name: 
 
 
University of Pittsburgh  
Protocol Principal Investigator:  
Robert E. Schoen, M.D., M.P.H. * 
 
 
 
 
 
Professor of Medicine and Epidemiology 
 
 
 
 
 
University of Pittsburgh Medical Center 
200 Lothrop St, Mezzanine Level, C Wing, 200 Lothrop Street 
Pittsburgh, PA  15213 
 
 
 
 
 
Telephone:  412-648-7086 
 
 
 
 
 
Fax: 412-648-7080 
 
 
 
 
 
rschoen@pitt.edu 
 
Organization:   
 
 
University of Pittsburgh 
Investigator: 
 
 
 
Olivera J. Finn, Ph.D. † 
 
 
 
 
 
University of Pittsburgh School of Medicine 
 
 
 
 
 
Chair, Department of Immunology 
 
 
 
 
 
E1040 Biomedical Science Tower 
 
 
 
 
 
Pittsburgh, PA  15262 
Telephone:  412-648-9816 
Fax: 412-648-9378 
E-mail:  ojfinn@pitt.edu  
 
Organization: 
 
 
Mayo Clinic 
Statistician: 
 
 
Nathan R. Foster, M.S. † 
 
 
 
200 First Street, SW, Rochester, MN  55905 
 
 
 
Telephone:  507-284-5051 
 
 
 
Fax:  507-266-2477 
 
 
 
E-mail:  foster.nathan@mayo.edu 
 
 
 
 
 
 
* Investigator having NCI responsibility for this protocol  
† Study Contributor(s) not responsible for patient care 
 
 

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Participating Organizations: 
 
Organization and Site Principal Investigator 
Site Co-investigators 
University of Pittsburgh Medical Center – PA015  
200 Lothrop Street, Pittsburgh, PA  15213 
 
Robert Schoen, M.D., M.P.H. 
Phone: 412-648-7086 
Fax: 412-648-7080 
Email: rschoen@pitt.edu 
Olivera J. Finn, Ph.D. 
Phone: 412-648-9816 
Fax: 412-648-9378 
Email: ojfinn@pitt.edu 
 
John McKolanis, Ph.D. 
Cell phone: 412-508-7671 
Fax:  412-383-8098 
Email: mckolani@pitt.edu 
Mayo Clinic in Rochester, MN – MN026 
200 First Street Southwest, Rochester, MN  55905 
 
Lisa A. Boardman, M.D. 
Phone: 507-284-2511 
Fax: 507-266-4371 
Email: Boardman.lisa@mayo.edu 
Paul J. Limburg, M.D., M.P.H. 
Phone: 507-284-2511 
Fax: 507-266-4371 
Email: Limburg.paul@mayo.edu 
 
 
University of Puerto Rico – PR008 
PR Cancer Center, PMB 371, PO Box 70344  
San Juan, PR  00936-8344 
 
Marcia Cruz-Correa, M.D., Ph.D. 
Phone: 787-759-0306 
Fax:  787-758-8303 
Email:  Marcia.cruz1@upr.edu 
Priscilla Magno-Pagatzaurtundua, M.D. 
Phone:  787-620-8716 x 223 
Fax: 787-758-8303 
Email: Priscilla.magno@upr.edu 
 
Mariella C. Rodriguez Suarez, M.D. 
Phone: 787-206-3915 
Fax: 787-538-8303 
Email: marerodz@gmail.com 
Massachusetts General Hospital – MA034 
Institute for Technology Assessment, 101 Merrimac 
Street, Boston, MA  02114 
 
Chin Hur, M.D. 
Phone: 617-724-4411 
Fax: 
Email: chur@mgh-ita.org 
None 
Thomas Jefferson University – PA121 
132 South 10th Street, 1170 Main, Philadelphia, PA 
19107 
 
David Kastenberg, M.D. 
Phone: 215-955-8108 
Fax: 215-955-3965 
Email: david.kastenberg@jefferson.edu 
 
 
Leo Katz, M.D. 
Phone: 215-955-8108 
Fax: 215-955-3965 
Email: leo.katz@jefferson.edu 
Daniel Quirk, M.D. 
Phone: 215-955-8108 
Fax: 215-955-3965 
Email: Daniel.quirk@jefferson.edu 

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Kansas City VA Hospital – MO029 
Department of Veteran’s Affairs, 4801 E. Linwood 
Blvd. (151), Kansas City, MO  64128 
 
Ajay Bansal, M.D. 
Phone: 816-861-4700 
Fax: 816-861-1110 
Email:  ajay.bansal@va.gov 
 Amit Rastogi, M.D. 
Phone: 816-861-4700 
Fax: 816-861-1110 
Email:  amit.rastogi@va.gov 
Fox Chase Cancer Center – PA086 
333 Cottman Avenue, Philadelphia, PA 19111 
 
David Weinberg, M.D., M.Sc. 
Phone:  215-214-1424 
Fax: 215-214-1425 
Email: David.weinberg@fccc.edu 
Stephen Heller, M.D. 
Phone:  215-214-1424 
Fax: 215-214-1425 
Email: Stephen.heller@fccc.edu 
Minhhuyen Nguyen, M.D. 
Phone:  215-214-1424 
Fax: 215-214-1425 
Email: minhhuyen.nguyen@fccc.edu 
Jeffrey Tokar, M.D. 
Phone:  215-728-2577 
Fax: 215-728-3639 
Email: Jeffrey.tokar@fccc.edu 
 
IND Sponsor: 
 
NCI, DCP 
 
IND# 
 
 
#15885 
 
Agent(s)/Supplier: 
MUC1 peptide, U. of Pittsburgh/Poly ICLC adjuvant: Oncovir, Inc.  
Contract # 
 
HHSN261201200042I 
 
Protocol Version Date: August 22, 2016   
 
Protocol Revision or  
 
Amendment #  
Version 5.0, Amendment 6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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CONTACTS 
Questions: 
Contact Name: 
Test schedule 
Study visits and procedures 
Specimen handling 
Lynda Dzubinski  
Lead Study Coordinator 
University of Pittsburgh Medical Center 
Phone: 412-648-9116; Fax: 412-648-9924 
Email:  lyd1@pitt.edu 
Subject eligibility, Test schedule 
Intervention 
Delays/Interruptions/Adjustments 
Adverse events, Forms completion 
Paraffin-embedded biospecimens 
April Felt 
CPN Research Base Quality Assurance Specialist and 
Pathology Coordinator 
Phone: 507-538-0268    Fax: 507-266-3722 
E-mail:  felt.april@mayo.edu 
Adverse Events 
Pat McNamara 
CPN Research Base  AdEERS Coordinator 
Phone: 507-266-3028     Fax: 507-284-9628 
E-mail:  mcnamara.patricia@mayo.edu 
CPN Lead Site Coordinator 
 
Colleen Garvey 
CPN Research Base Program Coordinator 
Phone: 507-284-2180     Fax: 507-266-4371 
E-mail: garvey.colleen@mayo.edu 
Protocol Development 
Sharon Kaufman 
CPN Research Base Senior Research Protocol 
Specialist  
Phone: 507-293-1605     Fax: 507-266-4371 
E-mail: kaufman.sharon@mayo.edu  
Regulatory 
Administrative 
Karrie Fursa 
CPN Research Base Research Protocol Specialist  
Phone:  507-266-2218    Fax:  507-266-4371 
E-mail:  fursa.karrie@mayo.edu  
Registration/Randomization 
Unblinding of Study Agents 
CPN Registration Office (8:00-4:30 Central Time) 
Phone: 507-284-4130; Fax: 507-284-0885 
E-mail: random01@mayo.edu 
Monitoring 
Anne Holland 
CPN Research Base Compliance Coordinator 
Phone: 507-293-7795   
Email: Holland.anne@mayo.edu   
All other biospecimens 
Biospecimens collection and shipment  
Roxann M. Neumann, RN, BSN, CCRP 
CPN Research Base Biospecimen Resource Manager 
Phone: 507-538-0602    Fax: 507-284-8105 
E-mail: neumann.roxann@mayo.edu  

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SCHEMA 
 
Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Vaccine in Patients with Newly 
Diagnosed Advanced Adenomas 
 
 
 
 
Protocol Title 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Target population 
• 
Male and female participants between 40 and 70 years of age 
• 
Recent diagnosis (within 1 year) of ≥1 advanced adenoma defined as: an adenoma ≥ 1 cm in size, 
or with villous or tubulovillous histology, or with high-grade (or severe) dysplasia. 
• 
Informed Consent 
Screening Evaluation (n = 120) 
• 
Office visit, physical exam, laboratory studies (to confirm eligibility), and verification of advanced 
adenoma status 
Registration/Randomization (n = 110 eligible participants; Week 0) 
Assuming 8% ineligibility after Week 0 screening 
MUC1 Vaccine Injection  
(See Section 7.1 for Schedule) 
(n=55 eligible participants) 
Placebo (normal saline) Injection 
(See Section 7.1 for Schedule) 
(n=55 eligible participants) 
Pre-Registration 

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Study: Parts 1 and 2 
• 
Vaccine vs. placebo injection with blood sampling for titer at weeks 0 (pre-injection titer), 2, and 
10 weeks  
• 
Completion of Part 1: Titer collection at week 12.  
• 
Part 2: Week 16, 28 and 40 telephone monitoring.   
• 
Titer collection at week 52 (pre-booster titer). 
• 
Week 53: booster vaccine vs. placebo injection 
• 
Completion of Part 2: Week 55 Titer collection (post booster), followed by telephone call follow 
up at week 57.  
• 
Endpoints:  
o Comparison of the  immunogenicity at week 12 of a MUC1 peptide vaccine with 
adjuvant (administered at 0, 2, and 10 weeks) (Part I endpoint) 
o To evaluate the ability of the vaccine to elicit a long-term memory response (Key Part 
II endpoint) 
o To assess adverse events to the MUC1 peptide vaccine in comparison to placebo 
during Parts I and II 
Part 3: Post Intervention Follow Up 
(n = 45 expected evaluable participants per arm) 
• 
Monitoring for adenoma recurrence (Weeks 57 - 156) 
• 
Telephone monitoring approximately every 6 months post booster administration.  
• 
Titer collection near timing of surveillance colonoscopy (approximately year 3) 
• 
Completion of Part 3: Post colonoscopy follow up and obtaining of tissue blocks from surveillance 
colonoscopy  
• 
Endpoint: 
o To compare the adenoma recurrence rate from surveillance exams occurring at least 
1 year and up to 3 years after Week 0 vaccine administration - MUC1 peptide vaccine 
vs. placebo (Part III key secondary endpoint). 
Off Study 

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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 
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 
Poly-ICLC – Polyinosinic-Polycytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose 
(Hiltonol®) 
PKR – Protein kinase receptor 
SAE – Serious adverse events 
T52 – Antibody titer at week 52 
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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TABLE OF CONTENTS 
 
Cover Page .................................................................................................................................................... 1 
Participating Institutions .............................................................................................................................. 2 
Contacts ........................................................................................................................................................ 4 
SCHEMA ........................................................................................................................................................ 5 
Glossary ........................................................................................................................................................ 7 
 
1. OBJECTIVES 
1.1        Primary Objective .................................................................................................................... 11  
1.2        Secondary Objectives .............................................................................................................. 11 
1.3        Translational Objectives .......................................................................................................... 11 
 
2. BACKGROUND ...................................................................................................................................... 11 
2.1 
Study Disease: Advanced Adenomas ...................................................................................... 16 
2.2 
Study Agent: MUC1 Vaccine (MUC1 peptide/Poly-ICLC) ........................................................ 16 
2.3 
Rationale ................................................................................................................................. 16 
2.4 
Studies Planned in the Proposed Clinical Trial ........................................................................ 17 
 
3. SUMMARY OF STUDY PLAN ................................................................................................................. 19 
3.1 
Study Parts .............................................................................................................................. 19 
3.2 
Study Design............................................................................................................................ 20 
3.3 
Vaccine and Clinical Endpoints ............................................................................................... 20 
 
4. PARTICIPANT SELECTION ..................................................................................................................... 21 
4.1 
Pre-Registration ...................................................................................................................... 21 
4.2 
Registration/Randomization ................................................................................................... 22 
4.3 
Inclusion of Women and Minorities ....................................................................................... 23 
4.4 
Recruitment and Retention Plan............................................................................................. 23 
 
5. AGENT ADMINISTRATION .................................................................................................................... 23 
5.1 
Dose Regimen and Dose Groups ............................................................................................. 23 
5.2 
Vaccine Administration ........................................................................................................... 23 
5.3  
Run-in Procedures ................................................................................................................... 24 
5.4 
Concomitant Medications ....................................................................................................... 24 
5.5 
Contraindications .................................................................................................................... 24 
5.6 
Dose Modification ................................................................................................................... 24 
5.7 
Adherence/Compliance .......................................................................................................... 24 
 
6. PHARMACEUTICAL INFORMATION ..................................................................................................... 24 
6.1 
Study Agent (IND#15885, NCI, DCP) ....................................................................................... 24 
6.2 
Reported Adverse Events and Potential Risks ........................................................................ 26 
6.3 
Availability ............................................................................................................................... 27 
6.4 
Agent Distribution  .................................................................................................................. 27 
6.5  
Agent Accountability  .............................................................................................................. 27 
6.6 
Packaging and Labeling ........................................................................................................... 27 
6.7  
Storage .................................................................................................................................... 28 

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       6.8 
Participant Pre-Registration and Registration/Randomization  ............................................. 28 
6.9 
Blinding and Unblinding Methods .......................................................................................... 30 
6.10 
Agent Destruction/Disposal .................................................................................................... 30 
 
7. CLINICAL EVALUATIONS AND PROCEDURES ....................................................................................... 31 
7.1 
Schedule of Events .................................................................................................................. 31 
7.2 
Baseline Testing/Prestudy Evaluation ..................................................................................... 34 
7.3 
Evaluation During Study Intervention ..................................................................................... 34 
7.4 
Evaluation at the Completion of Study Intervention .............................................................. 35 
7.5 
Post-Intervention Follow Up Period ....................................................................................... 35 
7.6  
Methods for Clinical Procedures ............................................................................................. 35 
 
8. CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION ................................................................. 35 
8.1 
Primary Endpoint .................................................................................................................... 35 
8.2 
Secondary and Translational Endpoints .................................................................................. 35 
8.3 
Off Agent Criteria .................................................................................................................... 36 
8.4 
Off Study Criteria .................................................................................................................... 37 
8.5  
Study Termination ................................................................................................................... 37 
 
9. CORRELATIVE/SPECIAL STUDIES .......................................................................................................... 38 
9.1 
Rationale for Methodology Selection ..................................................................................... 38 
9.2 
Comparable Methods ............................................................................................................. 38 
 
10. SPECIMEN MANAGEMENT................................................................................................................... 38 
10.1 
Laboratories ............................................................................................................................ 38 
10.2 
Collection, Handling, and Shipping Procedures ...................................................................... 38 
10.3 
Tissue Banking ......................................................................................................................... 40 
 
11. REPORTING ADVERSE EVENTS AND DEVIATIONS ............................................................................... 41 
11.1 
Adverse Events and Deviations ............................................................................................... 41 
11.2 
Serious Adverse Events ........................................................................................................... 44 
 
12. STUDY MONITORING ........................................................................................................................... 45 
12.1 
Data Management .................................................................................................................. 45 
12.2 
Case Report Forms .................................................................................................................. 45 
12.3 
Source Documents .................................................................................................................. 45 
12.4 
Data and Safety Monitoring Plan ............................................................................................ 46 
12.5 
Sponsor or FDA Monitoring .................................................................................................... 46 
12.6 
Record Retention .................................................................................................................... 46 
12.7 
CRADA/CTA ............................................................................................................................. 47 
 
13. STATISTICAL CONSIDERATIONS ........................................................................................................... 47 
13.1 
Study Design/Description ....................................................................................................... 47 
13.2 
Randomization/Stratification .................................................................................................. 48 
13.3 
Accrual and Feasibility ............................................................................................................ 49 
13.4 
Primary Objective, Endpoint, Analysis Plan ............................................................................ 49 
13.5 
Secondary Objectives, Endpoints, Analysis Plans ................................................................... 49 

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13.6 
Reporting and Exclusions ........................................................................................................ 50 
13.7 
Evaluation of Toxicity .............................................................................................................. 50 
13.8 
Evaluation of Response ........................................................................................................... 51 
13.9 
Interim Analyses...................................................................................................................... 52 
13.10 
Ancillary Studies ...................................................................................................................... 52 
 
14. ETHICAL AND REGULATORY CONSIDERATIONS .................................................................................. 53 
14.1 
FDA Form 1572 ....................................................................................................................... 53 
14.2 
Other Required Documents .................................................................................................... 53 
14.3 
Institutional Review Board Approval ...................................................................................... 53 
14.4 
Informed Consent ................................................................................................................... 54 
14.5 
Submission of Regulatory Documents .................................................................................... 54 
14.6 
Other ....................................................................................................................................... 54 
 
15. FINANCE, EXPENSES, AND/OR INSURANCE ........................................................................................ 55 
 
REFERENCES ................................................................................................................................................ 55 
 
INFORMED CONSENT TEMPLATE ............................................................................................................... 58 
 
APPENDICES ................................................................................................................................................ 69 
 
 
APPENDIX A. Performance Status Criteria .......................................................................................... 70 
 
 
APPENDIX B. Recruitment and Retention Plan Template .................................................................. 71 
 
 
APPENDIX C. Was it Worth It Questionnaire ...................................................................................... 79 
 
       APPENDIX D. Pre- and Post-Vaccine Risk, Regret, and Symptom Surveys......................................... 80 
 
       APPENDIX E. Vaccine Report Card ....................................................................................................... 92 
 
       APPENDIX F. Calculation of NAS Score ................................................................................................ 97 
 
 
 

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1. OBJECTIVES 
 
1.1  Primary Objective 
The primary objective of this trial is to compare the  immunogenicity at week 12 of a MUC1 peptide 
vaccine with adjuvant (administered at 0, 2, and 10 weeks) in participants with a history of an advanced 
adenoma, randomized to receive MUC1 peptide vaccine versus placebo (Part I endpoint). 
 
1.2 Secondary Objectives 
Secondary objectives which correlate with the planned parts of the study include: 
• 
To evaluate the ability of the vaccine to elicit a long-term memory response.  We will administer a 
booster injection of the vaccine or placebo at week 53.  Anti-MUC1 antibody response will be assessed 
at week 55 and compared to the week 52 pre-booster vaccine level (T55/T52). (Part II key secondary 
endpoint). 
• 
To compare the adenoma recurrence rate from surveillance exams occurring at least 1 year and up to 3 
years after Week 0 vaccine administration – MUC1 versus placebo (Part III key secondary endpoint).  
• 
To compare the adenoma recurrence rates between MUC1 and placebo by excluding the following types 
of adenomas. These adenomas are excluded since they may represent missed or residual adenomas 
from the baseline exam. These analyses are exploratory. 
o Participants with adenomas ≤ 5 mm, 
o Participants with adenomatous tissue which may represent residual adenoma at the site of the 
previous advanced adenoma, 
o Participants with adenomatous tissue detected in the same segment of the bowel as the 
previous advanced adenoma.  
• 
To assess adverse events to the MUC1 peptide vaccine in comparison to placebo during Parts I and II. 
• 
To assess patient reported injection site reaction events from the Vaccine Report Card. 
 
1.3 Translational Objectives 
• 
To compare the anti-MUC1 antibody titer at the time of surveillance colonoscopy for the purpose of 
evaluating the anti-MUC1 antibody response in relation to adenoma recurrence. Since surveillance 
colonoscopy is generally at 3 years after an advanced adenoma, this titer will typically be obtained at 
approximately week 156. 
• 
To evaluate MUC1 expression on baseline advanced adenomas and on recurrent adenomas detected at 
surveillance colonoscopy. Based on current knowledge of MUC1 expression and function in tumor cells, 
MUC1 negative adenomas are not expected to grow as immune escape variants. This has never been 
tested before, and the trial will provide an appropriate setting to study this issue.   
• 
To evaluate levels of circulating myeloid derived suppressor cells (MDSC) in the vaccinated and the 
placebo group and correlate with anti-MUC1 antibody levels and adenoma recurrence. 
To establish a biospecimen repository archive including live cells, plasma, and germline DNA for future 
immunologic (e.g. MUC1-specific T cells) and other assays (systems biology approach to detect 
differences between responders and non-responders), testing not currently accommodated within the 
budget of this trial.  
 
2. BACKGROUND   
     Randomized controlled trials demonstrate that endoscopic removal of adenomatous polyps reduces 
cancer incidence1, 2. However, there are many more adenomas than cancers, adenomatous polyp 

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recurrence rates are high, and repeated colonoscopic surveillance to monitor and remove recurrent 
adenomas is invasive, expensive, and associated with medical risk. Furthermore, surveillance 
colonoscopy is frequently misapplied, with excessive colonoscopy in low risk individuals and inadequate 
colonoscopy in some high risk individuals 3. Immunotherapy targeting antigens known to be aberrantly 
expressed on colon cancers and polyps offers the potential for a relatively non-invasive and non-toxic 
prevention strategy, and because of the specificity of the immune response and its long-term memory, 
offers the potential for prolonged protection.  Data suggest that aberrant expression of tumor antigens 
is subject to immune surveillance. During evolution from premalignant lesion to tumor, tumor-specific 
antibodies and T cells can be identified that in many animal models and human studies have been 
correlated with better prognosis. In a large study in colon cancer, that has now been repeated numerous 
times and in different types of tumors, infiltration of primary tumors with T cells was the best predictor 
of increased survival, surpassing even the cancer stage predictive value 4. MUC1 vaccines to boost 
immune responses have been tested in colon cancer patients with advanced metastatic disease with a 
clinical response between 10% and 14%5. While the immune responses induced were by and large weak 
due to the generally immunosuppressed state of patients with advanced disease, in 22 studies that  
measured vaccine induced immune responses, humoral immunity was seen in 59% of patients and 
cellular immunity in 44%5.  The limited effect of vaccine therapy in established cancer is now known to 
be due to numerous immunosuppressive mechanisms that develop in the cancer patient over time, 
caused either by the tumor or the immunotoxicity of standard cancer therapy, or both. Drugs, such as 
ipilimumab, are under development or being employed to modulate the tumor microenvironment to 
favor vaccine efficacy. However, most of these drugs are highly toxic in addition to being very expensive. 
 
An opportunity to bypass these barriers is presented by the discovery that many of the tumor antigens 
in cancer vaccines are also expressed on precursor lesions, e.g. adenomatous polyps as precursors to 
colon cancer, PanINs to pancreatic cancer and CINs to cervical cancer, suggesting that immunization of 
patients with pre-malignant lesions before the tumor and cytotoxic therapy suppresses the immune 
response is possible and may be preferred. Our hypothesis is that a vaccine that elicits or boosts 
immune surveillance early in the oncogenic process will prevent malignant disease by eliminating 
premalignant lesions and preventing their recurrence and their progression to cancer.  We are testing 
this hypothesis in the best elucidated pathway of premalignant to malignant progression, adenomatous 
polyp to colon cancer. The antigen we propose is MUC1, a tumor-associated antigen abnormally 
expressed on polyps and colon cancer 6, 7, and the population for the planned intervention is individuals 
with advanced adenomas, a group at high risk for colorectal cancer, even years after initial diagnosis 8.  
 
MUC1: Mucins are large glycoproteins that consist of an extended polypeptide core that is heavily 
glycosylated by O-linked carbohydrates. Mucin 1 (MUC1) is a high molecular weight (>200,000 dalton) 
type I transmembrane glycoprotein. MUC1 is produced by cells of epithelial origin and expressed on the 
apical surface of these cells as they form glands. MUC1 is expressed by normal epithelial cells but in low 
levels, polarized to the apical surface, and with extensive glycosylation. MUC1 is a cell surface mucin 
that is able to induce a specific immune response9, 10.  When cells undergo malignant transformation 
they produce hypoglycosylated MUC1 that has lost luminal polarity and is expressed at a much higher 
level than on normal cells. These characteristics allow its recognition by the immune system resulting in 
low-titer anti-MUC1 antibodies and MUC1 specific cytotoxic T-lymphocytes (CTL). Patients with 
adenocarcinomas of the breast, pancreas, and large bowel have T cells and antibodies that are directed 
to MUC1 11. The naturally occurring weak response is thought to be secondary to the lack of induction of 
MUC1 specific T-helper (Th) cells 12.  A MUC1 vaccine that can boost that immune response, especially 
effector pathways that induce MUC1-specific Th cell responses, may be effective in controlling or 

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curtailing tumor growth.  MUC1 is characterized by a large number of tandem repeats of 20 amino acids 
in the extracellular domain, which are quite immunogenic when underglycosylated, the form expressed 
on tumor cells 13, 14.  Recent work with T cells suggests that the immune response is directed to peptide 
and glycopeptide epitopes from the tandem repeat region exposed on the hypoglycosylated tumor form 
of MUC1.  During neoplastic transformation, the amount of MUC1 produced by tumor cells increases 
and its glycosylation decreases thus increasing the number and density of epitopes that serve both as 
immunogens as well as targets of the immune response.  The MUC1 molecule is also of interest because 
it binds β-catenin 15, 16 as well as intermediates in the ras signaling pathway 17 promoting cell 
transformation.  Thus, immunization against this molecule may affect premalignant cells in several 
different ways.  Cytotoxic T cells generated by a MUC1 vaccine may directly destroy premalignant cells, 
while the antibodies may be involved not only in direct destruction of cells through antibody-dependent 
cell-mediated cytotoxicity (ADCC) or complement mediated lysis, but also by blocking signaling 
pathways that promote further neoplastic transformation.  
 
Abnormal MUC1 expression has been a target for both active and passive immunotherapy of cancer in 
many pre-clinical and clinical studies18-20. Targeting a molecule that is critical for cancer progression and 
survival lessens the chance that MUC1 negative mutant cancer cells would arise. In a recent NCI 
workshop on tumor antigen prioritization, MUC1 was ranked as the overall #2 priority target (only 
slightly behind WT1) 21. Its priority was a result of 25 years of preclinical studies in animal models and 
almost 20 years of clinical trials, primarily in the therapeutic setting. 
 
MUC1 vaccines:  MUC1 proteins, peptides, glycopeptides or DNA-based vaccines have been widely used 
with or without adjuvants, loaded on DCs, with cytokines and immune stimulatory molecules, or 
engineered in various viral vectors, for treatment of cancer. These have been administered to patients 
with advanced disease and compromised immune systems. Even though the immune response induced 
by the vaccines was infrequent and at low levels, both humoral and cellular responses have been 
reported. In a meta-analysis published in 2006 of all clinical trials of MUC1 colon cancer vaccines 
published since 1985, consisting of 32 studies involving 527 colorectal cancer patients and accounting 
for 108 publications, utilizing MUC1 antigens that varied from whole tumors to individual peptides with 
a variety of adjuvants, toxicity was mild in the vast majority of studies, and manifest primarily as 
injection site symptomatology and flu like symptoms 5. At the University of Pittsburgh Cancer Institute 
we have run seven clinical trials using the unglycosylated VNTR 100mer MUC1 peptide representing 5 
tandem repeats, a highly immunogenic form not found on normal epithelial cells. 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 22. The vaccine was safe and induced IgG 
and T cells responses in some patients. Two of 16 patients 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. The second Part 
I/II trial used MUC1 100mer-peptide-loaded on DC. The vaccine was well-tolerated and non-toxic in 12 
patients enrolled. The patients were followed for over four years and four of the twelve patients were 
alive without evidence of recurrence at 5 years. 
 
Two decades of clinical trials targeting MUC1in a variety of cancers in over 1200 patients were recently 
reviewed 23. Ongoing trials registered at clinicaltrials.gov identify an additional 2000 patients planned 
for anti-MUC1 therapy 23. The presence of anti MUC1 immunity in cancer patients favorably affects 
tumor development and prognosis23.  
 

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MUC1 Peptide: Many types of vaccines have been tested by numerous investigators around the world 
incorporating a variety of MUC1 antigenic forms made immunogenic through the use of different 
adjuvants23. Other forms, such as endogenously expressed MUC1 peptides via a plasmid, synthetic 
mRNA or a virus vector comprise only a minority of MUC1 vaccines. Synthetic MUC1 peptides have 
ranged from 16mer to 105mer in length and, with very few exceptions, they have all been derived from 
the VNTR tandem repeat sequence. The synthetic MUC1 tandem repeat peptides have been conjugated 
to immunogenic proteins or substrates, such as keyhole limpet haemocyanin (KLH) or mannan, mixed 
with various adjuvants such as Bacille de Calmette et Guērin (BCG), partially purified mycobacteria cell-
wall skeleton and monophosphoryl lipid A (MPL) (DETOX), Quillaja Saponaria extract (QS-21), incomplete 
Freund’s adjuvant (IFA) and QS-21 and MPL (SB-AS2).  The 3-D structure of the MUC1 tandem repeat 
using 20, 40 and 60aa-long peptides has been characterized 24 and the optimal number of repeats for 
induction of immune responses or detection of antibodies in ELISA assays has been determined 25.  The 
findings suggested that increasing numbers of tandem repeats elicited increasing titers of antibodies as 
well as detection levels of serum IgG in ELISAs.  Attempts to synthesize long MUC1 peptides were 
successful first through manual synthesis and later also achieved through automatic synthesis.  The 
optimal length was considered to correspond to 5 tandem repeats, 100aa, below which detection was 
weaker and above which no further benefit was seen.  Thus the 100mer peptide became the vaccine 
antigen and the facility for production of the certified peptide for clinical use was established at the 
University of Pittsburgh.   
 
Poly ICLC Adjuvant:  Polyinosinic-Polycytidylic acid stabilized with poly-L-lysine and 
carboxymethylcellulose (Poly-ICLC, Hiltonol®) is a synthetic, non-replicating double-stranded ribonucleic 
acid (dsRNA), with no specific genetic message. It acts as viral-mimic with broad innate and adaptive 
immune enhancing, vaccine adjuvant, antiviral and antiproliferative effects 25, 26. These are mediated 
partly by its induction of a ‘natural mix’ of interferons (IFNs), cytokines, and chemokines, activation of 
natural killer [NK] cells, myeloid dendritic cells via TLR3 and MDA5, T4 and T8 cells, and activation of 
several nuclear and cytoplasmic enzyme systems (oligoadenylate synthetase [OAS], the dsRNA 
dependent protein kinase [PKR], RIG-I Helicase, and MDA5) that are involved in antiviral and antitumor 
host defenses. It has been shown to have broad gene regulatory actions as well. Poly-ICLC is currently 
being developed for the treatment of various disease indications in humans. Older studies in advanced 
cancer patients had shown a maximum tolerated dose of over 200 mcg/kg intravenously (IV), but Poly-
ICLC has been administered intramuscularly (IM) 2 to 3 times weekly for years at doses of 10 to 50 μg/kg 
in patients with gliomas, multiple sclerosis or HIV/AIDS, and is well tolerated 27-29. Three recent phase II 
multicenter trials of Poly-ICLC 20 mcg/kg IM 3 times weekly in over 180 patients with gliomas have 
confirmed safety and potential efficacy (see poly ICLC investigational brochure). Poly-ICLC is also being 
used for various cancer vaccine platforms in about two dozen, ongoing phase I/II clinical trials in patients 
with glioma, hepatoma, lymphoma, prostate, cervical, ovarian, breast, colon, and pancreatic cancers.  
 
About 400 patients have been safely treated in those trials to date (see poly ICLC investigational 
brochure). The most common side effects of low-dose Poly-ICLC are temporary discomfort at the 
injection site and occasional transient malaise that lasts for several hours. Occasionally, patients on low-
dose Poly-ICLC have developed a flu-like syndrome with fever, chills, and malaise. This syndrome 
typically resolves in 12 to 24 hours, responds to acetaminophen, and does not recur on subsequent 
dosing. Subcutaneous dosing, especially with vaccine, can also result in transient injection site erythema. 
Poly-ICLC has also been used nasally in a recent phase I randomized dose escalation trial in humans 
(N=50), and was well tolerated. 
 

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Vaccines for Prevention   
Other than viral vaccines for cancers of known viral origin, vaccines for prevention of cancer have not 
received sufficient attention.  Yet, there are many non-viral antigens that are differentially expressed 
between normal and cancer cells, such as MUC1, that are perceived by the immune system as foreign 
and to which immune responses can be safely generated through vaccination.  In preclinical animal 
models of human cancer, these vaccine-elicited immune responses have prevented cancer development 
or cancer progression. These studies have served as the basis for the first clinical feasibility study of the 
MUC1 peptide vaccine in individuals with the history of advanced adenoma who are considered at 
increased risk for developing colon cancer34.  This study showed that the vaccine consisting of 100mcg of 
the synthetic 100mer MUC1 peptide admixed with the TLR-3 agonist Hiltonol as adjuvant, induced anti-
MUC1 IgG and long term immune memory thus confirming its immunogenicity.  The study also showed 
that individuals with above normal numbers of circulating myeloid derived suppressor cells (MDSC) were 
prevented from responding to the vaccine.  The randomized placebo-controlled trial described in this 
protocol will confirm the vaccine immunogenicity and its dependence on the MDSC and compare 
adenoma recurrence in vaccine responders vs. non-responders.   
 
Colorectal Adenomas 
MUC1 is overexpressed and hypoglycosylated on premalignant lesions such as adenomatous polyps, and 
its expression is significantly greater with higher degrees of dysplasia 7. MUC1 is functionally important 
in the maintenance of the malignant phenotype. Thus, induction of an immune response against MUC1 
in the setting of pre-malignancy, such as in patients with adenomatous polyps, may protect from polyp 
recurrence as well as from progression to cancer. 
 
 
Mouse model of MUC1 vaccine for colon cancer prevention 
Mouse experiments have been performed over the years to test the immunogenicity, safety and efficacy 
of MUC1 vaccines.  One of the best mouse models has been the MUC1 transgenic mouse that expresses 
human MUC1 under its own promoter and thus maintains tissue specific expression, including 
undergoing changes in expression during tumorigenesis. Most vaccines tested in human clinical trials 
showed both high immunogenicity and high efficacy in mouse models. It should be emphasized that this 
result was always achievable in the prevention setting and worked in the therapeutic setting only when 
the tumors were extremely small (e.g. 3-day tumors).  Vaccination in the setting of a larger or metastatic 
tumor was never successful. Experiments in spontaneous mouse tumor models, though more labor 
intensive and of longer duration, are a good reflection of the immunosurveillance of the emerging tumor 
by the immune system and more closely resemble human disease than transplantable tumor models.  A 
well-known model of human colon carcinogenesis is the Apc/MIN mouse that develops spontaneous 
adenomatous polyps that can develop into cancer. This mouse was crossed to the MUC1 transgenic 
mouse and both the polyps and the resulting tumors expressed the abnormal MUC1 and could be 
Normal 
Tumor 
O-linked 
oligosaccharides 
HGVTSAPDTRPAPGSTAPPA 
Figure1: Abnormal MUC1 is overexpressed and 
hypoglycosylated. Hypoglycosylated MUC1 
exposes the disaccharide T antigen and the shorter 
monosaccharide Tn antigen attached to the 
protein backbone of MUC1 molecules. 

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targeted by a MUC1 vaccine.  In the MIN mouse, a MUC1-based vaccine caused flattening of adenomas 
and significantly reduced the number of large adenomas 35. Immunization was successful in generating a 
MUC1-specific immune response. 
 
Two recent MUC1 vaccine studies in mouse tumor models of colorectal cancer were recently performed. 
In an IL-10-/- mice that spontaneously develop inflammatory bowel disease (IBD) and progress to colitis 
associated colon cancer (CACC), crossed with MUC1 transgenic mice, a MUC1 vaccine that induced 
humoral and cellular anti-MUC1 immunity reduced inflammation and prevented development of CACC 
36. The same result was obtained in a dextran sodium sulfate (DSS) model of CACC where the 
MUC1vaccine reduced chronic colitis, prevented development of dysplasia, and extended survival 37.  
While this is a different route of colon cancer development in that these are inflammatory models, the 
model shows both efficacy and safety of the vaccine-induced anti-MUC1 immunity.   
 
2.1  Study Disease: Advanced Adenomas 
 
Advanced adenomas (AAs) are defined as pre-neoplastic adenomatous polyps that are either: 1) ≥ 1 cm 
in size, 2) demonstrate villous or tubulovillous histology, or 3) have severe or high grade dysplasia. 
Advanced adenomas occur in about 5-10% of patients undergoing screening colonoscopy.  Individuals 
with AAs are a high risk group. Studies show that individuals having an advanced adenoma have a 2 fold 
or more risk of having a recurrent AA compared to individuals with non-advanced adenomas 38, 39, and 
more importantly, are at higher risk for subsequent colorectal cancer, even years later 8, 40. Patients with 
AA are an appropriate group to focus on for prevention. Low levels of anti-MUC1 IgG can be detected in 
patients with advanced adenomas 41. Most recently, we performed a pilot study of MUC1 vaccine in 
patients with a prior history of advanced adenoma, though not necessarily recently diagnosed advanced 
adenomas, and the vaccine was well tolerated with no significant toxicity 34.  
 
2.2 Study Agent: MUC1 Vaccine (MUC1 peptide/Poly-ICLC)  
 
A certified clinical grade 100-amino acid synthetic MUC1 peptide with the molecular structure of H2N-
(GVTSAPDTRPAPGSTAPPAH)5-CONH2, will be synthesized at the University of Pittsburgh Peptide 
Synthesis Facility. The adjuvant, toll like receptor (TLR) 3 agonist, Poly-ICLC (Hiltonol®), will be supplied 
by Oncovir Inc. (Washington, DC) in single-dose vials of 1mL solution containing 2mg poly-IC, 1.5mg 
poly-L-lysine, and 5mg sodium carboxymethylcellulose in 0.9% sodium chloride, adjusted to pH 7.6-7.8 
with sodium hydroxide. The vaccine will consist of 100 micrograms (0.1mg) of the MUC1 100mer 
peptide dissolved in 50mcL (0.05mL) of sterile saline, admixed with 500mcg (0.5mg) of Hiltonol® in 
250mcL (0.25mL), for a total injection volume of 300mcL (0.3mL). 
 
2.3  Rationale  
 
Completed Feasibility study of MUC1 Vaccine at U. of Pittsburgh   
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 34. In the 39 participants that 
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 response 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 
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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 didn’t 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.  
 
Adverse Events   
Over 150 vaccinations were administered in the pilot study. No adverse events above grade 1 were 
identified, and no unanticipated adverse events were observed. Most participants developed erythema 
with soreness at the injection site. Some developed short lived fever and muscle aches, which respond 
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.  
 
Figure 2: 
 
 
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.  
 
2.4 Studies Planned in the Proposed Trial 
 
Evaluation of anti-MUC1 antibody titer and MUC1 expression in adenomas in relation to adenoma 
recurrence  
Anti-MUC1 IgG will be measured at w12 and w55 to measure the immune response to the vaccine in 
comparison to placebo, and at the time of the endpoint surveillance colonoscopy to examine the 
relationship between antibody titer and adenoma recurrence. In addition, sections of the qualifying 
advanced adenoma and of any recurrent adenomas will be obtained.  Comparison of tumor associated 
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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MUC1 antigen expression on the recurrent adenomas in relation to antibody response, and comparison 
among vaccine responders, non-responders, and the control group are planned.  
 
Evaluation of anti-MUC1 antibody responses and pre-vaccination levels of circulating MDSC 
Heparinized blood will be collected at week 0, 2, 10, and 12 and live PBMCs stored in DMSO and LN2 at  
-70 to -80oC. We plan measurements of levels of circulating MDSC in all participants.  We know from the 
feasibility study that higher levels of MDSC were associated with lack of generation of vaccine induced 
antibodies.  We will confirm this observation in a larger number of individuals and will evaluate MDSC 
levels as a variable influencing adenoma recurrence.  In the placebo group, we expect to have MDSC low 
and MDSC high individuals in whom we can determine if adenoma recurrence rates might correlate with 
MDSC.  
 
Using samples stored in the biorepository, eventually, stored PBMCs will be used to evaluate MUC1 
specific T helper and CTL responses.  These studies are more time intensive and expensive and funding 
for them will have to be obtained through other sources or other NCI grants. We do not anticipate 
difficulty obtaining funding for sophisticated immune assessments on this unique collection of clinical 
samples among participants undergoing a randomized trial of immunotherapy in a prevention setting. 
Within this trial, we are using T dependent antibody responses and T dependent memory responses as a 
surrogate marker of vaccine elicited T cells.     
 
Placebo Response   
There are several important reasons to include a placebo group. We do not know the frequency of 
spontaneous acquisition of antibodies to MUC1, nor do we have data on the natural history of 
fluctuation in antibody level over time. A control group with which to compare the antibody response 
and a control group with which to compare adenoma recurrence is essential.  
 
Exclusion of Individuals with Cancer    
We are intentionally not enrolling participants with cancer (within the previous 5 years), even early 
stage cancer. By the time a cancer is present, the immune system has been exposed to and has 
attempted to cope with the lesion for some time. Attesting to the value of an intact immune system, the 
antibody response rates observed in our preliminary study far exceed that observed in previous trials of 
participants with cancer. Even in the setting of advanced adenoma, the pilot study showed signs of 
immunosuppression (higher levels of MDSC) in some patients. All cancer patients have elevated levels of 
these and other immunosuppressive cell populations. 
 
How does the proposed trial differ from the completed feasibility study?   
The completed study was performed to assess immune response, evaluate toxicity, and to trial 
recruitment, consent, and vaccine administration. The completed study was a resounding success in 
terms of enrollment, follow up, absence of adverse events, and immune response. The eligibility criteria 
included a history of advanced adenoma that could have been diagnosed years prior. The mean time 
from advanced adenoma diagnosis to vaccination in included participants was 824 days with a range up 
to 3500 days. As such, participants had interim colonoscopy exams prior to vaccination, and assessment 
of the effect of vaccine on adenoma recurrence is not possible.  A significant difference in the proposed 
trial is the synchronization of vaccine administration with diagnosis of advanced adenoma such that a 
meaningful assessment of the vaccine on adenoma recurrence is attainable. A clinical endpoint is 
needed to advance immunotherapy in the prevention setting. 
 

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Laboratory Biomarkers  
 
 
The most appropriate biomarker of vaccine efficacy is the immune response. We will measure the major 
T cell dependent anti-MUC1 antibody IgG isotype which requires MUC1 specific T cells to promote 
isotype switching by B cells from IgM. We will largely focus on anti IgG to MUC1, as that antibody 
isotype is easier to measure and more reproducibly induced. We will also measure MDSC levels to 
evaluate the relationship between MDSC and vaccine response. 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 or adenoma recurrence and changes in the serum 
cytokine and chemokine profiles. The tissue sections of adenomas will be also be useful in exploring the 
underlying hypothesis that vaccination can impair MUC1 expression and adenoma progression. 
 
Conclusions and Implications 
The robust antibody response obtained in our pilot trial in participants with a premalignant advanced 
adenoma challenges the assumption that tumor-associated antigens like MUC1 are subject to immune 
tolerance.  Our data indicate that tumor or treatment-induced immune suppression was more likely 
responsible for ineffective immunization in cancer patients. The high level of antibody response in 
participants with pre-malignant disease attests to the promise of immunotherapy against tumor 
antigens as a means of prevention. Lack of toxicity will allow application of the vaccine in healthy as well 
as younger individuals with strong immune systems. 
 
The proposed trial will add substantively to the pilot trial, because it offers synchronization of diagnosis 
and vaccine administration, and allows assessment of a clinical endpoint, adenoma recurrence. As the 
first randomized trial of immunoprevention, the trial offers a pioneering, innovative opportunity in 
cancer prevention research. The development of a biorepository will facilitate ancillary biomarker 
studies in this unique cohort and promise multiple opportunities for collaboration in and outside the NIH 
to make the trial even more productive over time.  
 
3. SUMMARY OF STUDY PLAN 
 
3.1 Study Parts   
 
There are 3 Parts planned. Each Part will provide salient data on MUC1 immunoprevention, with 
continuation through Part III providing insight on the clinical efficacy of the vaccine.  
 
1. 
Part 1 will include participant follow up to week 12 and will permit assessment of MUC1 vaccine 
response compared to placebo.  
2. 
Part 2 will include participant follow up to week 56 and will permit assessment of MUC1 immune 
memory response to a booster dose of vaccine compared to placebo.  
3. 
Part 3 will include participant follow up to week 156 and will permit assessment of the clinical 
endpoint of adenoma recurrence in participants with vaccine compared to placebo. Assessment of 
MUC1 expression on recurrent adenomas will allow assessment of whether vaccination can impair 
MUC1 expression and adenoma progression. 
 
The vaccine is manufactured at the FDA certified peptide facility of the University of Pittsburgh. The 
vaccine will consist of 100 micrograms (0.1mg) of MUC1 100mer peptide dissolved in 50 microliters 
(0.05mL) of sterile saline, admixed with 500 micrograms (0.5mg) of the adjuvant poly-ICLC (Hiltonol®) in 
250 microliters (0.25mL) volume, for a total injection volume of 300 microliters (0.3mL). Poly-ICLC is a 

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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. 
Participants randomized to placebo will receive an identically appearing injection of sterile saline. 
 
3.2 Study Design  
 
This is a randomized, double-blind, placebo controlled phase II trial designed to elicit immune responses 
to abnormal MUC1. A 1-year booster vaccine will be administered to assess the presence of T cell 
dependent immune memory. Participants will be randomized on a 1:1 scheme. The protocol will call for 
injections at week T0, T2, and T10, and a booster injection at week T53. Monitoring of the immune 
response will be at each time point prior to injection, T0, T2, T10 and at week T12, T52, T55 (post 
booster), and at the time of the endpoint surveillance colonoscopy up to T156, for a total of 7 
measurements of MUC1 immune response.  For details regarding study visits and assessments, see 
Section 7. 
 
Up to 120 participants will be approached for pre-registration, and assuming an 8% ineligibility rate, 
approximately 110 participants will be randomized to either vaccine or placebo injections and followed 
up to 3 years for the primary and secondary endpoints. A dropout rate of up to 10% is assumed between 
baseline and year 1, and an additional 10% drop out rate is assumed between year 1 and year 3 
(termination of follow-up). 
 
Eligible participants will have had an advanced adenoma that was completely resected as reported by 
endoscopic assessment. Advanced adenomas will be defined as: 1) ≥ 1 cm in size; 2) demonstrates 
villous or tubulovillous histology; or 3) have severe or high grade dysplasia.  We anticipate enrolling 
approximately 4 participants per month across all sites for the first 3-6 months, and then 8 participants 
per month across all sites until we reach the accrual target. Accrual is expected to be completed in 18 
months. Total study duration for Part 1 is expected to be about 22 months, followed by an additional 12 
months for Part 2 and 24 months for Part 3.   
 
Intervention Arms:  Participants meeting study criteria will be randomly assigned to receive one of two 
interventions according to the following intervention schedule: 
• 
Muc1/poly ICLC 0.3 mL subcutaneous study vaccine in the upper thigh  
• 
Normal saline injection 0.3 mL subcutaneous in the upper thigh  
 
3.3 Vaccine and Clinical Endpoints  
 
The response to the vaccine will be evaluated by monitoring changes in IgG anti-MUC1 antibody titer 
ratio; defined as t12/t0, where t0 is the “initial titer” measured prior to vaccination, and t12 is the “final 
titer” drawn at 12 weeks. For the primary endpoint, the titer measured 2 weeks after the 3rd vaccination, 
at week 12, will be compared to the baseline titer at week 0.  Because IgG is more commonly induced 
and more likely to be detected because of the better quality of reagents, IgG levels will be the indicator 
of immungenicity. A titer ratio of ≥2 will be considered an immune response. The use of a titer ratio 
permits a uniform definition for an immunologic response regardless of the baseline level of MUC1 
antibody. The titer ratio at week 12 will mark the close of Part 1 of the trial. The assessment of the 
response to the booster vaccine will be evaluated by examining the week 55 titer to the titer at week 52, 
prior to receipt of the booster vaccine. Once again, a titer ratio of ≥2 for the T55/T52 comparison will be 
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The titer ratio of 2:1 as a measure of immune response was chosen in part from the infectious disease 
literature where this ratio is often employed as a marker of immune response. This ratio was commonly 
attained (44%) in our pilot study in participants with advanced adenoma 34. A titer increase of ≤2 may 
also have clinical efficacy. We have no preliminary information to identify what titer ratio may be 
associated with a clinical endpoint. The measurement of the response to the booster vaccine and 
communication with the patient regarding response (week 55) will mark the close of Part 2 of the trial.  
 
The week 156 endpoint will be adenoma recurrence. Adenoma prevention trials testing 
chemoprevention regimens have been performed for a variety of compounds ranging from beta 
carotene, calcium, folate, aspirin, DFMO, dietary modification, fiber supplementation, etc. Although 
there have been repeated calls for trials using other intermediate endpoints such as aberrant crypt foci, 
adenoma recurrence remains the mainstay in examining the efficacy of an agent in relation to colorectal 
cancer. The adenoma is a reproducible measure, with a reproducible, standardized nomenclature 
implemented by pathologists. 
 
4. 
PARTICIPANT SELECTION 
 
4.1 Pre-Registration 
 
4.1.1 
Pre-Registration Inclusion Criteria 
4.1.1.1 History of at least one of the following conditions in the previous 12 months: 
o Colorectal adenoma(s) ≥ 1 cm in maximal diameter 
o Colorectal adenoma(s) with villous or tubulovillous histology 
o Colorectal adenoma(s) with high grade (severe) dysplasia. 
4.1.1.2 Presumptive evidence that all adenomatous lesions, including qualifying advanced 
adenoma, have been completely removed.  
4.1.1.3 Age 40 - 70 years of age at time of registration/randomization.   Note:  Individuals 
under the age of 40 with advanced adenomas have a high risk of familial disease.  
Individuals over the age of 70 begin to show signs of impaired immune function due 
to age.   
4.1.1.4 Ability to understand and the willingness to sign a written informed consent 
document. 
4.1.1.5 Willingness to undergo screening tests and procedures. 
4.1.1.6 Willingness to provide blood samples for toxicity monitoring and research purposes. 
4.1.1.7 Not pregnant or nursing. Note:  A negative (serum or urine) pregnancy test must be 
documented ≤ 7 days prior to registration/randomization for women of childbearing 
potential.   
4.1.1.8 Willingness to employ adequate contraception through Week 53 of the study.  Note:  
The effects of the MUC1 vaccine on the developing human fetus at the dose 
specified in this study are unknown. For this reason, women of childbearing 
potential and men must agree to use adequate contraception (hormonal, barrier 
method of birth control, abstinence) prior to study entry and for the period of active 
vaccination (through Week 53).  Should a woman become pregnant or suspect she is 
pregnant while participating in this study, she should inform her physician 
immediately. 
 

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4.1.2 
Pre-Registration Exclusion Criteria 
4.1.2.1   History of any colorectal cancer 
4.1.2.2   History of other malignancy ≤ 5 years prior to the Registration/Randomization 
                evaluation, with the exception of basal cell or squamous cell skin cancer. 
4.1.2.3    Presence of an active acute or chronic infection or uncontrolled illness including, 
                but not limited to unstable congestive heart failure, unstable angina pectoris,  
                cardiac arrhythmia, or psychiatric illness/social situations that would limit 
                compliance with study requirements. 
4.1.2.4   Acquired immunosuppressive diseases such as active HIV infection or congenital 
               diseases of immunity.  
4.1.2.5   History of heritable cancer syndrome (FAP, HNPCC). 
4.1.2.6   History of auto-immune disease such as, but not restricted to, inflammatory bowel 
               disease, systemic lupus erythematosis, rheumatoid arthritis, ankylosing spondylitis, 
               scleroderma, multiple sclerosis, Hashimoto’s thyroiditis, or Grave’s disease.  
4.1.2.7   Current or planned use of immunomodulators including: infliximab, 6-MP 
               (mercaptopurine), methotrexate, cyclosporine, or other immunomodulatory drugs. 
4.1.2.8   History of allergic reactions attributed to compounds of similar chemical or biologic  
               composition to the study agent. 
4.1.2.9   Pregnant women, because the teratogenic or abortifacient effects of the study 
                agents remain incompletely defined.   
4.1.2.10 Breastfeeding women, because there is an unknown but potential risk for adverse 
                events in nursing infants secondary to treatment of the mother with the study  
                agents. 
4.1.2.11. Diagnosis of nonalcoholic steatohepatitis (NASH) and a NAFLD (nonalcoholic fatty 
                 liver disease) activity score (NAS) ≥5. NOTES and EXCEPTIONS:  NAS is based on 
                 findings from a liver biopsy.   Participants with NAS of ≤2 are eligible for 
                 enrollment. Participants with NAS of 3-4 must be discussed with the Principal 
                 Investigator and DCP before enrollment to consider other risk factors (i.e., obesity, 
                 alcohol intake). Participants with a prior diagnosis of NASH and no available NAS 
                 must be discussed with the Principal Investigator and DCP before enrollment to 
                 considered risk factors (i.e., obesity, alcohol intake). See Appendix F. 
 
4.2 Registration/Randomization 
 
4.2.1 
Registration/Randomization Inclusion Criteria 
 
4.2.1.1 ECOG performance status ≤1 (Karnofsky ≥70%; see Appendix A). 
4.2.1.2 Hemoglobin greater than 90% of the lower limit of institutional normal. 
4.2.1.3 Normal marrow and organ function, obtained ≤ 28 days prior to 
Registration/Randomization, and defined as follows: 
• 
Platelets ≥ 100 B/L (109/L) 
• 
WBC > 2.5 B/L (109/L) 
• 
AST (SGOT), ALT (SGPT), alkaline phosphatase, total bilirubin, BUN, and 
creatinine ≤ 1.5 x institutional upper limit of normal 
4.2.1.4 ANA test result excludes overt autoimmune disease.  Note:  Test result may be 
reported in any of the following formats:  ≤ 1:160, negative, or < 1.0. 

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4.2.2 
Registration/Randomization Exclusion Criteria 
 
4.2.2.1  Receiving any other investigational agent ≤ 3 months prior to 
               Registration/Randomization, except innocuous agents with no known interaction 
               with the study agent (e.g., standard dose multivitamins or topical agents for limited 
               skin conditions).  
4.2.2.2  Any use of oral corticosteroids ≤ 12 weeks prior to Registration/Randomization. 
 
4.3 
Inclusion of Women and Minorities 
 
Both men and women and members of all races and ethnic groups are eligible for this trial. Refer to the 
Recruitment, Retention, and Adherence (RR&A) Plan Template for details (Appendix B). 
 
4.4 
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 Template (Appendix B) as the basis for their plans.  At a minimum, these plans will be 
reviewed annually.  
 
5. 
AGENT ADMINISTRATION 
 
Intervention will be administered on an outpatient basis. Reported adverse events (AEs) and potential 
risks are described in Section 6.2. It should be noted that pharmacy personnel (or other appropriate 
personnel to whom this task is delegated) will not be blinded to the intervention assignment. Every 
effort should be taken to maintain the blinded nature of the study.  For example, the time required to 
formulate and dispense the active injection should be no longer than the time to formulate and 
dispense the placebo injection. 
 
5.1 
Dose Regimen and Dose Groups  
 
The vaccine will consist of 100 micrograms (0.1mg) of MUC1 100mer peptide dissolved in 50 microliters 
(0.05mL) of sterile saline, admixed with 500 micrograms (0.5mg) of the adjuvant poly-ICLC (Hiltonol®) in 
250 microliters (0.25mL) volume, for a total injection volume of 300 microliters (0.3mL). Vaccine will be 
administered at weeks 0, 2, and 10 weeks. A booster vaccine will be administered at week 53 to 
establish the presence of T helper cell memory to the antigen.   An identical-appearing placebo injection 
will be prepared using 0.9% NaCl.  
 
5.2 
Vaccine Administration 
 
The vaccine will be administered by appropriate site personnel subcutaneously in the anterior thigh 
approximately 20 cm inferior to the inguinal ligament. The vaccine will be administered into the same 
thigh on all 4 occasions for vaccine delivery. The vaccine site may demonstrate erythema after 
administration. This erythema can persist even to the timing of the next vaccine dosing. Erythema is not 
a contraindication to repeat vaccination. However, at the discretion of the investigator, repeat 
vaccination may be delayed, but not to exceed the protocol limits. It is also possible to inject the vaccine 

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into the opposite thigh, if necessary.  Preferred windows for visits and vaccine administration and 
sampling are provided in Section 7.1.  
 
5.3  
Run-in Procedures 
 
Not applicable. 
 
 
5.4 
Concomitant Medications 
 
All medications (prescription and over-the-counter), vitamin and mineral supplements, and/or herbs 
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.  
 
If a study participant is prescribed corticosteroids or immunomodulators during the course of the study, 
the situation will be discussed among the treating physician, the study chair, and the medical monitor to 
determine whether or not the participant should be allowed to continue on study. 
 
5.5  
Contraindications 
 
Contraindications to study participation include receiving other investigational agents, presence or 
occurrence of an active acute or chronic infection or undercurrent illness, use of immunomodulators 
pregnancy, or breastfeeding (as applicable). See Section 4.2 for details regarding initial eligibility.      
 
5.6 
Dose Modification 
 
The vaccine will be administered in the protocol-defined dosage for all participants on all occasions.  
 
5.7 
Adherence/Compliance 
 
5.7.1  All vaccine/placebo will be administered by appropriately trained study personnel at each site.  
               Vaccine/placebo administration will be documented on the Intervention Administration CRF.  
5.7.2      Individuals who receive the Week 0, Week 2, and Week 10 injections will be considered 
               evaluable for the primary endpoint.  Individuals who receive the Week 53 injection will be 
               considered evaluable for the Part II key secondary endpoint.  Individuals from whom data and  
               specimens are collected for a subsequent clinical colonoscopy occurring at least 1 year (52  
               weeks) after the Week 0 injection will be considered evaluable for the Part III key secondary 
               endpoint.  
 
6. 
PHARMACEUTICAL INFORMATION 
 
6.1 
Study Agent (IND # 15885, NCI, Division of Cancer Prevention)   
 
MUC1 Peptide 
The MUC1 peptide is composed of a 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 

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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. 
 
Placebo  
The placebo injection will contain normal saline (0.9% NaCl) provided by each individual Participating 
Organization.  
 
 
 
 
 
 
 
 

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6.2  Reported Adverse Events and Potential Risks 
 
The side effects listed in the table below are based on a variety of previous studies that were similar to 
this study in some ways but different in important ways (including stronger doses) that may have led to 
different side effects.  In the previous study that was most similar to this study, no autoimmune disease 
or serious side effects were identified. 
 
Possible Side Effects of the MUC1 – poly-ICLC vaccine: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Common, Some May Be Serious 
In 100 people who receive the injection, more than 20 may have: 
• 
Redness at injection site (erythema) 
• 
Pain/soreness at injection site 
• 
Flu-like symptoms, which may include fever  chills, headache, fatigue, muscle pain, and joint pain 
• 
Night sweats 
• 
Loss of appetite 
• 
Low albumin blood test result (a type of protein in the blood) 
 
The redness and soreness generally resolve within a few days to a week. Generally, acetaminophen 
(Tylenol®) is sufficient for pain relief.  The flu-like symptoms generally resolve within 12-24 hours.   
Acetaminophen (Tylenol®) generally helps with these symptoms if they occur.  
 
Occasional, Some May Be Serious 
In 100 people who receive the injection, 4 to 20 may have: 
• Low white blood cell count (cells that fight infections) 
• Low platelet count (cells that help the blood clot in order to stop bleeding) 
• Anemia (which may cause tiredness, or may require blood transfusion) 
• Abnormal liver function test results 
 
Rare, Some May Be Serious 
In 100 people who receive the injection, 3 or fewer may have: 
• 
Hives, shortness of breath, or an allergic reaction that is life-threatening 
• 
Immune reaction to his or her own tissue (autoimmune diseases) or if present, may be made 
worse.  
 
 
6.3  
Availability 
 
MUC1 100mer peptide and Poly-ICLC will be supplied by the University of Pittsburgh and sent to each 
participating site’s research pharmacy upon receipt of a completed CPN Study Agent Order Form. The 
vaccine/saline placebo injection will be prepared by each participating organization’s pharmacy (or 
other appropriate designated personnel) within 8 hours prior to clinical administration.  Normal saline 
for placebo injection will be provided by each participating organization.  Study agent will be supplied by 
and shipped from: 
 

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Olivera Finn, Ph.D., E1040 Biomedical Science Tower, Pittsburgh, PA  15262 
Telephone:  412-648-9816; Fax: 412-648-9378; E-mail:  ojfinn@pitt.edu  
 
6.4 
Agent Distribution 
 
Agent will only be distributed to participating organizations after documentation of IRB approval of the 
DCP-approved protocol and consent is provided to DCP, collection of all Essential Documents is 
complete (see DCP website for description of Essential Documents), and Drug Shipment Authorization 
has been confirmed. 
 
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 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.  
 
After receipt of the final site close out visit report by the CPN Compliance Coordinator, any remaining 
study agent may be destroyed per institutional guidelines. 
 
Forms required for study agent ordering, accountability, and return are available on the CPN website:  
http://cancerpreventionnetwork.org  
 
6.6 
Packaging and Labeling 
 
Participating site pharmacy personnel will not be blinded to the study intervention.  However, the 
pharmacy personnel will be required to label the injection supplied for each participant in such a 
manner as to not provide any information about intervention assignment to the site investigators.  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 or placebo 0.3mL.  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, if 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.  
 
6.8     Pre-Registration and Registration/Randomization 

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6.8.1 Participant Pre-Registration 
 
6.8.1.1 To pre-register a participant, access the Cancer Prevention Network (CPN) web page 
(https://cancerpr.ipower.com/member/MAY2013-01-01.shtml  ) and enter the remote pre-
registration application.  The remote pre-registration application is available 24 hours a day, 7 days a 
week.  Back up and/or system support contact information is available on the Web site.  If unable to 
access the Web site, call the CPN Registration Office at (507) 284-2753 between 8:00 a.m. and 4:30 
p.m. Central Time (Monday through Friday). 
 
The instructions for remote pre-registration are available on the CPN web page 
(https://cancerpr.ipower.com/member/MAY2013-01-01.shtml ) and detail the process for 
completing and confirming participant pre-registration.  Prior to initiation of protocol screening, this 
process must be completed in its entirety and a CPN Participant ID number (PID) must be available 
as noted in the instructions.  It is the responsibility of the individual pre-registering the participant to 
confirm the process has been successfully completed.  Participant pre-registration via the remote 
system can be confirmed in any of the following ways: 
• 
Contact the CPN Registration Office (507) 284-2753.  If the participant was fully pre-
registered, the Registration Office staff can access the information from the centralized 
database and confirm the pre-registration. 
• 
Refer to “Instructions for Remote Pre-Registration” in section “Finding/Displaying 
Information about a Registered Participant” within the Remote Registration/Randomization 
User’s Manual available for download from the CPN website. 
 
6.8.1.2 At the time of pre-registration, the following will also be verified: 
• 
IRB approval at 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 to collect and store blood and/or tissue for 
future use in research to learn about, prevent, treat, or cure cancer. 
o Participant has/has not given permission to collect and store blood and/or tissue for 
future use in research about other health problems (for example:  Barrett’s 
esophagus. causes of diabetes mellitus, Alzheimer’s disease, and heart disease). 
o Participant has/has not given permission to send blood and/or tissue sample(s) to 
researchers at an outside institution. 
o Participant has/has not given permission to his/her doctor (or someone from the 
Cancer Prevention Network) to contact them in the future to ask them to take part 
in more research. 
 
 
6.8.1.3   Baseline (screening) evaluations must be completed within the guidelines specified on 
  
the Schedule of Events (See Section 7.1). 
 

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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/Randomization 
 
6.8.2.1  Fax to 507-284-0885 a completed Eligibility Checklist (see CRF packet) to the CPN 
Registration Office between 8:00 a.m. and 4:30 p.m. Central time, Monday through 
Friday. 
 
6.8.2.2 Randomization:  For details, see Section 13.2. 
  
6.8.2.3 Intervention on this protocol must commence at a CPN institution under the supervision of a 
CPN clinician. 
 
6.8.2.4 Intervention cannot begin prior to Registration/Randomization and must begin ≤ 14 days 
after Registration/Randomization. 
 
6.8.2.5 Pathology and colonoscopy reports confirming diagnoses must be sent ≤ 30 days post 
Registration/Randomization to the CPN QAS at CPN Operations Office, Lanmark 2, 200 First Street 
Southwest, Rochester, MN  55905; or FAX: 507-266-3722, Attention CPN QAS. 
 
6.8.2.6 Once the intervention assignment has been ascertained by the CPN Registration Office, the 
appropriate blinded study agent information (MUC1 vaccine or placebo/saline injection) will be 
communicated to the designated data manager/nurse/pharmacist at the participant’s Participating 
Organization. The name of this contact person is to be entered in the designated space on the 
eligibility checklist so the Registration Office personnel have it for each participant at the time of 
registering/randomizing the participant. Make sure this contact person will be available at the time 
of the registration so he or she can receive the information from the Registration Specialist. This 
contact person may not be involved in assessing adverse events or any other outcome measure and 
should not be the same person listed on page one of the eligibility checklist form as the person 
completing the form. The last page of the eligibility checklist form should provide the source of 
communication for the contact person, either fax or email, and the appropriate contact information. 
 
       6.8.2.7   Stratification Factors:   
• 
Number of advanced adenoma on qualifying colonoscopy: ≥ 3 vs. < 3 
• 
Gender: male vs. female 
 
After the participant has been registered on to the study, values of the stratification factors will be 
recorded.  Randomization will be performed by CPN personnel.  The CPN electronic-based 
randomization system will be utilized to ensure that randomization of participants to appropriate 
study arms while balancing the stratification variables is carried out successfully. 
 
6.9 
Blinding and Unblinding Methods 
 
There are two distinct situations in which it will be deemed appropriate to break the randomization 
assignment for participants enrolled onto this current trial: 

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• 
In the event of an emergency for an individual participant. 
• 
Serious Adverse Event (SAE) that fulfills the criteria for expedited reporting to the FDA. 
In these situations, Participating Organization personnel may assume the participant is on active agent 
and call the CPN Registration Office within one business day to receive unblinding information.   The 
study name/number, participant identifier, and participant initials will be required to break the 
randomization code.   The Participating Organizations are responsible for notifying the medical monitor 
at DCP, NCI of the unblinding event. 
 
6.10 
Agent Destruction/Disposal 
 
At the completion of investigation and after submission of the site final close out visit report by the CPN 
Compliance Coordinator, all unused study agent will be destroyed on site according to institutional 
SOPs.   

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7. 
CLINICAL EVALUATIONS AND PROCEDURES 
7.1 
Schedule of Events 
Parts I and II 
Study Visit 
Pre-
Registration 
Screening/
Baseline1 
Registration/ 
Randomization 
Week 02 
Week 2 
Week 4 
(+/- 7 
days) 
Week 6 
(+/- 7 
days) 
Week 
10 
 
Week 12 
 
Weeks 
16, 28, 
and 40 
(+/- 7 
days) 
Week 52 
 
Week 53 
Booster 
 
Week 55 
 
Week 57 
(+/- 7 
days) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
History and 
Physical 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
Vital Signs 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
Baseline 
Symptoms 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
Medications 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CBC w/5-part diff., 
platelets 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
Blood chemistry 
panel (potassium, 
sodium, chloride, 
bicarbonate, 
creatinine, serum 
glucose, BUN, 
total bilirubin, alk 
phos, and uric 
acid) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
Antinuclear 
antibody (ANA) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
AST/SGOT;  
ALT/SGPT 
 
X 
 
X 
 
 
X 
X 
 
X 
 
X 
 
Research blood3 
 
X3 
 
X3 
 
 
X3 
X3 
 
X3 
 
X3 
 
Obtain medical 
record release, if 
applicable 
 
X 
 
 
 
 
 
 
 
 
 
 
 

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Part III 
Study Visit/Event 
Weeks 88, 104, 130  
(+/- 10 days) 
Week 156 
(Year 3) 12 
Update medical/surgical history 
 
X 
Phone call 
X10 
 
Concomitant medications 
X 
X 
Research blood3 
 
X3 
Obtain medical record release, if applicable 
 
X 
Obtain colonoscopy reports and specimens 
 
X 
QOL Questionnaire 
 
X11 
1. Baseline evaluations must occur after pre-registration and must be completed ≤ 28 days prior to registration/randomization.  
2. Week 0 injection must be administered ≤ 14 days after registration/randomization. The date on which the injection is administered will become the 
“zero” time point from which all subsequent time points will be measured.  
3. Research blood (blood for immunology assays and other endpoints) must be collected M-Th only and shipped overnight for next day analysis. 
4. Operative notes, endoscopy reports, and/or pathology reports must be reviewed locally to confirm that the candidate meets at least one of the entry 
criteria specified in inclusion criterion 4.1.1.1. Participants will need to registered/randomized within 1 year from the initial polyp removal, unless 
evidence of an advanced adenoma is identified at the subsequent colonoscopy, in which case the timing for eligibility will start anew.  Note: if 
Study Visit 
Pre-
Registration 
Screening/
Baseline1 
Registration/ 
Randomization 
Week 02 
Week 2 
Week 4 
(+/- 7 
days) 
Week 6 
(+/- 7 
days) 
Week 
10 
 
Week 12 
 
Weeks 
16, 28, 
and 40 
(+/- 7 
days) 
Week 52 
 
Week 53 
Booster 
 
Week 55 
 
Week 57 
(+/- 7 
days) 
Obtain 
colonoscopy 
reports and 
specimens4,5 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test6 
 
X 
X 
X 
 
 
X 
 
 
 
X 
 
 
Vaccination 
(MUC1/POLY-ICLC  
or placebo) 
 
 
X 
X7 
 
 
X8 
 
 
 
X9 
 
 
Adverse Events 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Phone call 
 
 
 
 
X 
X 
 
 
X 
 
 
 
X 
QOL 
Questionnaire(s) 
 
 
X11 
 
 
 
 
 
 
 
X11 
X11 
 

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participants are scheduled for early repeat colonoscopy, such as within 12 months of the colonoscopy that identified the advanced adenoma, to 
insure complete removal of the qualifying lesion, they should be enrolled after that repeat colonoscopy insures that no residual adenoma is present. 
5. Endoscopy report and/or pathology report confirming qualifying advanced adenoma diagnosis as well as the fact that all polyps and adenomas have 
been removed must be submitted by FAX or email to the CPN Quality Assurance Specialist (QAS) within 30 days after registration/randomization. 
6. Pregnancy test (serum or urine) will be performed for female participants of childbearing potential at baseline/screening and prior to each injection 
(Week 0, 2, 10, and booster vaccine).  Week 0 pregnancy test does not have to be repeated if ≤ 7 days since baseline/screening test.  Should a woman 
become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. 
7. Week 2 injection may not occur less than 14 days after Week 0 injection. It may occur up to 28 days after the Week 0 injection. 
8. Week 10 injection should occur 7-10 weeks (ideally 8 weeks) after Week 2 injection. 
9. Week 53 booster should ideally occur as soon as possible after the week 52 monitoring test results are available. It may occur up to 4 weeks after the 
Week 52 visit. 
10. Telephone contact will be made to monitor concomitant medications, possible adenoma recurrence, and the timing of follow up surveillance 
colonoscopy. 
11. The Risk, Regret, and Symptom Questionnaire (Appendix D) will be administered before the Week 0 injection, after the Week 53 injection, and at the 
Week 156 visit.  The Was It Worth It (WIWI) Questionnaire (Appendix C) will be administered during the Week 55 visit. 
12. The timing of the follow up surveillance colonoscopy will vary among individuals and institutions.  Ideally, the participants will return at Week 156 (+/- 
4 weeks) to update their medical/surgical history, concomitant medications, and immune response.  If any clinical surveillance colonoscopies are 
scheduled between Weeks 52 and 156, it would be ideal to gather the updated med/surg history and concomitant medications within 2 weeks before 
the scheduled colonoscopies. If this is not possible, it will not be considered a protocol deviation. These data should still be gathered and the timing 
noted. Reports and specimens from the colonoscopy should be gathered within 30 days after the colonoscopy.  Colonoscopy and pathology reports 
must be submitted by FAX or email to the CPN Quality Assurance Specialist (QAS) within 30 days after the date of the procedure. 
 
Summary of Parameters for Visit Timing 
Week/Visit 
Window 
Ideal timing 
0 
Within 28 days of screening visit 
within 1 week 
2 
No earlier than 2 weeks and up to 4 weeks from week 0 injection 
2 weeks from week 0 injection 
10 
7 – 10 weeks from week 2 injection 
8 weeks from week 2 injection 
12 
10 – 21 days after week 10 injection 
2 weeks from week 10 injection 
52 
51 to 54 weeks from week 0 injection 
52 weeks 
53 
As soon as possible after week 52 monitoring tests return 
Within 4 weeks of week 52 visit 
55 
10 – 21 days from week 53 injection 
2 weeks 
156 
Within 4 weeks of any planned colonoscopy 
2 weeks before colonoscopy 
Note: If the visit/event takes place within the window specified above, it will not be considered a deviation. However, for consistency, every effort should be 
made to schedule visits and events according to the “ideal timing” column. The scheduling of subsequent injections should be based on timing of previous 
injection.   If sampling or injections are delayed, they should still occur (even after colonoscopy for week 156 titer, for example), and timing should be noted.  

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7.2 
Baseline Testing/Prestudy 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, documentation of any existing baseline 
symptoms, allergies, and concomitant medications, and baseline blood tests.  Baseline blood tests 
include CBC with 5-part differential, potassium, sodium, chloride, bicarbonate, creatinine, serum 
glucose, BUN, total bilirubin, alkaline phosphatase, uric acid, AST/SGOT, ALT/SGPT, and antinuclear 
antibody (ANA). Blood will also be drawn at baseline for the immune assay (IgG assay).  Authorization to 
obtain data and specimens from the clinical colonoscopies will be obtained. 
 
If participants are eligible and willing to participate, they will be registered to the study and randomized 
to one of two intervention arms (vaccine versus placebo/saline injection). Values of the stratification 
factors will be recorded and the CPN electronic-based randomization system will be utilized to ensure 
that randomization of participants to appropriate study arms, while balancing the stratification 
variables, is carried out successfully. 
 
7.3 
Evaluation During Study Intervention 
 
Vaccine or placebo/saline will be administered at weeks 0, 2, and 10, with a booster at week 53.  
Females of childbearing potential will be required to document negative pregnancy test prior to each 
injection.  Immune response will be tested 2, 10, 12, 52, 55, and 156 (Year 3).  Adverse events will be 
evaluated at regular time points after each injection (See Section 11.1 for details). 
 
At the Week 2 and Week 12 visits, if any erythema or induration injection site reactions are still present, 
the participant’s measurement of the diameter will be compared with the study team’s measurement 
for the purpose of validating the participant-reported measurement. 
 
Blood tests to monitor toxicity will be conducted at weeks 2, 10, 12, 52, and 55.  At weeks 2, 10, and 55, 
CBC with 5-part differential, AST/SGOT, and ALT/SGPT will be performed.  At week 12, AST/SGOT and 
ALT/SGPT will be performed.  Possible adverse events and concomitant medication information will be 
captured at each visit and by telephone at weeks 4, 6, 16, 28, and 40. All visits will involve informing the 
participant of the results of previous blood tests. 
 
Participants will undergo an evaluation at week 52, including a physical exam, blood tests for immune 
response and toxicity monitoring, discussions of the results of previous tests, discussions of possible 
adverse events and concomitant medications.,.  The following blood tests will be performed:  CBC with 
5-part differential, potassium, sodium, chloride, bicarbonate, creatinine, serum glucose, BUN, total 
bilirubin, alkaline phosphatase, uric acid, AST/SGOT, ALT/SGPT, and antinuclear antibody (ANA).   
 
Risk, Regret, and Symptom Questionnaires will be administered prior to the Week 0 injection and at 
weeks 53 and 156. The Was It Worth It (WIWI) Questionnaire will be completed at Week 55. 
 
 

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7.4 
Evaluation at Completion of Study Intervention 
 
The final blood tests for immune response and toxicity monitoring will take place at Week 55.  Those 
results will be provided, and discussions of adverse events and concomitant medications will take place 
at Week 57 by telephone, 
 
7.5 
Post-intervention Follow-up Period 
 
For the purpose of monitoring adenoma recurrence and concomitant medications, contact by telephone 
will be made approximately every six months until Week 156 (Year 3) or the time of reported adenoma 
recurrence.  Reports and specimens from any clinical colonoscopies will be obtained.   Immune response 
will be tested.  See Section 7.1 for details. 
 
7.6 
Methods for Clinical Procedures 
 
7.6.1 Vaccine injection procedure details  
See Section 5.2. 
 
7.6.2 Colonoscopy data and specimens 
Data will be abstracted from operative and pathology reports from clinical surveillance 
colonoscopies to confirm initial eligibility (Section 4.1.1.1) and to document any recurrence or 
new diagnosis.  Permission will be obtained, if applicable, from each participant to obtain 
paraffin blocks and/or unstained slides from any specimens removed during the clinical 
surveillance colonoscopies. 
 
8.  
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION 
 
8.1 
Primary Endpoint 
 
The primary endpoint for this study is to compare the ratio of the week 12 to week 0 IgG levels between 
the MUC1 vaccine and placebo.  It is hypothesized that this ratio will be increased in patients treated 
with the MUC1 vaccine as compared to patients receiving the placebo.  All randomized participants who 
are evaluated at week 0 and week 12 and have IgG values from those time points will be evaluable for 
the primary endpoint of this study using a modified intent-to-treat principle.   If we are missing the data 
for Week 0 or Week 12, we will be missing data for the analysis since the primary endpoint will compare 
the ratio of the Week 12 to Week 0 IgG levels between the MUC1 vaccine and the placebo. 
 
The measurement of vaccine-induced anti-MUC1 IgG will be determined by Enzyme-Linked 
Immunosorbent Assay (ELISA).  See Section 10.2.2. 
 
8.2 
Secondary and Translational Endpoints 
 
The secondary endpoints will include the following: 
 
• 
The Part I key secondary endpoint will be a comparison of the proportion of patients with at least a 
2-fold increase in the IgG ratio between the 2 arms at 12 weeks. 

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• 
The Part II key secondary endpoint will assess the booster response at week 55 vs. week 52 for the 
vaccine as compared to placebo. 
• 
The Part III key secondary endpoint will compare the adenoma recurrence rate from surveillance 
exams occurring at least one year and up to three years after Week 0 vaccine administration – 
MUC1 peptide versus placebo.   
 
In addition to these key powered endpoints for the 3 different parts, we will also assess the following 
additional secondary endpoints: 
 
• 
Comparison of adverse events between the MUC1 vaccine and placebo during Part 1 and 2. 
• 
Comparison of the adenoma recurrence rates between MUC1 and placebo by excluding the 
following types of adenomas. These adenomas are excluded since they may represent missed or 
residual adenomas from the baseline exam. These analyses are exploratory. 
o Participants with adenomas ≤ 5 mm, 
o Participants with adenomatous tissue which may represent residual adenoma at the site of 
the previous advanced adenoma, 
o Participants with adenomatous tissue detected in the same segment of the bowel as the 
previous advanced adenoma.   
• 
Assessment of participant-reported injection site reaction events from the Vaccine Report Card. 
 
In addition, we will assess the following translational endpoints: 
 
• 
To compare the anti-MUC1 antibody titer at the time of surveillance colonoscopy for the purpose of 
evaluating the anti-MUC1 antibody response in relation to adenoma recurrence. Since surveillance 
colonoscopy is generally at 3 years after an advanced adenoma, this titer will typically be obtained 
at approximately week 156. 
• 
To evaluate MUC1 expression on baseline advanced adenomas and on recurrent adenomas 
detected at surveillance colonoscopy. Based on current knowledge of MUC1 expression and 
function in tumor cells, MUC1 negative adenomas are not expected to grow as immune escape 
variants, but this has never been tested before and the trial will provide an appropriate setting to 
study this issue.   
• 
To evaluate levels of circulating myeloid derived suppressor cells (MDSC) in the vaccinated and the 
placebo group and correlate with anti-MUC1 antibody levels and adenoma recurrence (See Section 
10.2.2). 
• 
To establish a biospecimen repository archive including live cells, plasma, and germline DNA for 
future immunologic and other assays, for testing not currently accommodated within the budget of 
this trial. 
 
Where appropriate, secondary and translational analyses will be based on all randomized participants 
(i.e. adverse event analyses) or defined participant subgroups.   
 
8.3 
Off-Agent Criteria  
 
Participants may stop taking the study agent due to: completion of the planned intervention period, 
development of an adverse event or serious adverse event, inadequate agent supply, noncompliance, 
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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 7).  
 
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-randomization 
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 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.  The FDA also has the 
authority to discontinue the study at any time. 
 
 
 

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9. 
CORRELATIVE/SPECIAL STUDIES 
 
9.1 
Rationale for Methodology Selection 
 
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.  See Section 10.2.2 for details. 
 
9.2 
Comparable Methods 
 
This study will employ procedures that have been validated previously for clinical use. 
 
10. 
SPECIMEN MANAGEMENT  
 
10.1 
Laboratories 
 
Heparinized whole blood collected at all locations will be shipped to the University Of Pittsburgh School 
Of Medicine.  Dr. John McKolanis will receive and record the specimens, and he will also be responsible 
for processing the blood into plasma and PBMC.  PBMC will be frozen at -70 to -80oC in human serum 
with 20% DMSO and plasma will be frozen at -20oC.  Dr. McKolanis 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 additional 
biomarker studies.  
 
Unstained slides from tissue blocks of the qualifying advanced adenoma and for adenomas detected at 
the time of surveillance colonoscopy that determines adenoma recurrence (baseline and recurrent 
adenomas) will be collected at each site and shipped to the Mayo Clinic.  They will then be batched and 
shipped to the University of Pittsburgh for subsequent immunostaining and other assays. 
 
 
10.2 
Collection, Handling, and Shipping 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. 
 

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• 
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 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. 
 
Blood specimens will be sent to: 
Dr. John McKolanis, 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 
 
For tracking purposes, participating organizations will telephone or email the following two 
individuals to inform them that specimens are being sent to the University of Pittsburgh. 
 
1. Dr. John McKolanis,  
 
 
Email: mckolani@pitt.edu 
 
 
Cell phone: 412-508-7671 
2. Roxann Neumann, Biospecimens Resource Manager  
 
 
Email:  Neumann.roxann@mayo.edu 
 
 
Telephone:  507-538-0602 
 
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 a one-hour incubation the plates are washed five 
times and the substrate, p-nitrophenyl phosphate (Sigma-Aldrich), added to each well. The reaction is 

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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 
cells. 
 
10.2.3 Tissue Specimens 
 
Paraffin blocks and/or unstained slides from the polyps/adenomas removed during routine colonoscopy, 
pre- and post-intervention, will be requested from the institution at which the procedure was 
performed.   
 
Tissue paraffin sections will be deparaffinized by baking overnight at 59°C. Endogenous peroxidase 
activity will be eliminated by treatment with 30% H2O2 for 15 min at room temperature. Antigen 
retrieval will be performed by microwave heating in 0.1% citrate buffer. Nonspecific binding sites will be 
blocked with Protein Blocking Agent (Thermo-Shandon Corp). Sections will be immunostained with anti-
MUC1 antibody HMPV, which recognizes all forms of MUC1 by binding the epitope APDTR in the VNTR 
region in a glycosylation-independent manner (BD Pharmingen) and anti-MUC1 antibody VU-4H5 (Santa 
Cruz Biotechnology), which recognizes the epitope APDTRPAP in the VNTR region of hypoglycosylated 
MUC1 (Santa Cruz Biotechnology). Staining will be performed by the avidin-biotin peroxidase complex 
(ABC) method with a commercial kit (Vectastain ABC kit, Vector Laboratories). Color development will 
be performed by 3,3’Diaminobenzidine (DAB) kit (BD Pharmingen).  
 
Institutions that are unable to submit paraffin blocks may send five 5-micron unstained slides from each 
advanced adenoma as an alternative. Paraffin blocks and/or slides must be labeled with the participant 
ID number, specimen type, specimen number, and date of collection.  Every effort must be made to 
make certain the specimen number on the block and/or slide labels corresponds to the polyp or 
adenoma number reported on the Colonoscopy Report CRF. 
 
Send blocks/slides to: 
CPN PC Office (Study MAY2013-01-01) 
RO_FF_03_24-CC/NW Clinic 
200 First Street Southwest, Rochester, MN 55905 
 
10.3 
Tissue Banking 
 
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.  
 

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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 banking/long term storage to: 
Biospecimens Accessioning and Processing (BAP) Freezer 
ST SL-39, 150 Third Street Southwest, Rochester, MN  55902 
At study completion, remaining paraffin blocks and slides will be labeled (study number, participant ID 
number, specimen type, specimen number, date of collection) batched, and shipped for banking/long 
term storage to: 
CPN PC Office (Study MAY2013-01-01) 
RO_FF_03_24-CC/NW Clinic 
200 First Street Southwest, Rochester, MN 55905 
 
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 AND DEVIATIONS  
 
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. 
 
A list of AEs that have occurred or might occur (Reported Adverse Events and Potential Risks) can be 
found in Section 6.2, Pharmaceutical Information, as well as the Investigator Brochure or package insert.  
 
11.1 
Adverse Events and Deviations 
 
11.1.1 Reportable Adverse Events (AEs) 
 
All AEs that occur after the informed consent is signed and baseline assessments are completed must be 
recorded on the AE CRF (paper and/or electronic) whether or not related to study agent. 
 
11.1.2 AE Data Elements: 
 
The following data elements are required for adverse event reporting. 
• 
AE verbatim term 
• 
System Organ Class (SOC) 

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• 
Common Terminology Criteria for Adverse Events v4.0 (CTCAE) AE term 
• 
Event onset date and event ended date 
• 
Severity grade 
• 
Attribution to study agent (relatedness) 
• 
Whether or not the event was reported as a serious adverse event (SAE) 
• 
Whether or not the subject dropped due to the event 
• 
Outcome of the event 
 
11.1.3  Severity of AEs 
 
 
 
11.1.3.1 Identify the AE using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
4.0. The CTCAE provides descriptive terminology and a grading scale for each adverse event listed. A 
copy of the CTCAE can be found at 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
 
All AEs, including injection site reactions, will be assessed according to the CTCAE grade associated with 
the AE term. AEs that do not have a corresponding CTCAE term will be assessed according to the general 
guidelines for grading used in the CTCAE v4.0. as stated below.  AEs will be reported and evaluated by 
use of the standard Adverse Events case report form (CRF). 
 
CTCAE v4.0 general severity guidelines:  
 
Grade 
Severity 
Description  
1 
Mild 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
2 
Moderate 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental activities of daily living 
(ADL)*. 
3 
Severe 
Severe or medically significant but not immediately life-
threatening;hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self-care ADL**. 
4 
Life-threatening 
Life-threatening consequences; urgent intervention indicated. 
5 
Fatal 
Death related to AE. 
   
ADL 
*Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
**Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
 
 
 
 
 
 
 

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11.1.3.2  Injection Site Reactions 
 
Injection site reactions, a subset of all AEs, will also be reported by use of a participant-completed 
Vaccine Report Card, captured on a separate CRF, and reported to NCI, DCP. This report will not be part 
of the MDS.  The following guidelines will be used to evaluate the injection site reaction: 
 
Local Reaction 
to Injectable 
Product 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Pain 
Does not interfere 
with activity 
Repeated use of 
non-narcotic pain 
reliever > 24 hours 
or interferes with 
activity 
Any use of narcotic 
pain reliever or 
prevents daily 
activity 
Emergency room 
(ER) visit or 
hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
ER visit or 
hospitalization 
Erythema/ 
Redness* 
2.5 - 5 cm 
5.1 - 10 cm 
> 10 cm 
Necrosis or 
exfoliative 
dermatitis 
Induration/ 
Swelling** 
2.5 - 5 cm and does 
not interfere with 
activity 
5.1 - 10 cm or 
interferes with 
activity 
> 10 cm or 
prevents daily 
activity 
Necrosis 
* In addition to grading the measured local reaction at the greatest single diameter, the measurement 
should be recorded as a continuous variable. 
** Induration/Swelling should be evaluated and graded using the functional scale as well as the actual 
measurement. 
11.1.4 Assessment of relationship of AE to treatment 
 
 
The possibility that the adverse event is related to study agent will be classified as one of the following: 
not related, unlikely, possible, probable, definite. 
  
11.1.5 Follow-up of AEs 
 
All AEs, including lab abnormalities that in the opinion of the investigator are clinically significant, will be 
followed according to good medical practices and documented as such. 
 
11.1.6  Reporting Deviations 
 
A protocol deviation is any noted variance or difference in the conduct of the study from the written 
protocol plan.  All deviations will be reported by completing the DCP Deviation Reporting form available 
on the CPN website: https://cancerpr.ipower.com/member/Deviations.shtml 
 
The deviation reporting form will be completed in Word format and submitted by email to the DCP 
medical monitor (see Section 11.2.2.2 for contact information). 

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11.2 
Serious Adverse Events  
 
11.2.1 DEFINITION: Fed. Reg. 75, Sept. 29, 2010 defines SAEs as those events, occurring at any dose, 
which meet any of the following criteria: 
• 
Results in death 
• 
Is life threatening (Note: the term life-threatening refers to an event in which the patient was at 
risk of death at the time of the event; it does not refer to an event which hypothetically might 
have caused death if it were more severe). 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
Is a congenital abnormality/birth defect 
• 
Important medical events that may not result in death, be life-threatening or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed. 
 
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 form found at http://prevention.cancer.gov/files/clinical-trials/SAE_form.doc. 
 
11.2.2.2 
Contact the DCP Medical Monitor by phone within 24 hours of knowledge of the event.  
 
 
 
 
 
 
 
Luz Maria Rodriguez, MD, FACS 
 
 
 
 
 
 
National Institutes of Health, National Cancer Institute 
Division of Cancer Prevention 
 
 
 
 
 
 
9609 Medical Center Drive, Room 5E228 
 
 
 
 
 
 
Bethesda, MD 20892 
 
 
 
 
 
 
Phone:  240-276-7039 
 
 
 
 
 
 
Fax (with cover sheet, Attn:  Dr. L. Rodriguez):  240-276-7848 
 
 
 
 
 
 
Email (preferred):  rodrigul@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 and expectedness 
 
11.2.2.3 
The Lead Organization and all Participating Organizations will FAX or email written SAE 
reports to the DCP Medical Monitor within 48 hours of learning of the event using the paper SAE form. 

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The written SAE reports will also be FAX’ed or emailed to Dr. Robert Schoen, Study Principal Investigator 
and CCS Associates, DCP’s Regulatory Contractor.    
 
 
 
Robert Schoen, M.D. 
 
 
Email:  rschoen@pitt.edu 
 
 
Fax:  412-648-7080 
 
 
 
 
 
DCP’s Regulatory Contractor, CCS Associates: 
 
 
Email:  safety@ccsainc.com 
 
 
Fax:  650-692-4410 
 
Participating Sites will also FAX this form to the CPN Operations Office within 48 hours of learning of the 
event at fax 507-284-9628.  See the Data Management Plan (see CPN web site) sections “Data 
Collection” and “Data Entry and Processing” for further instructions as SAEs must also be recorded on 
the participant’s appropriate case report forms.   
  
11.2.2.4 
The DCP Medical Monitor and regulatory staff will determine which SAEs require FDA 
submission, per CFR 21 Section 312.32 
 
11.2.2.5 
The Lead Organization and all Participating Organizations will comply with applicable 
regulatory requirements related to reporting SAEs to the IRB/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 form in the appropriate format. Follow-up 
information should be sent to DCP as soon as available. SAEs that are determined to be at least possibly 
related to study intervention will be followed according to institutional standards of care until resolved. 
 
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 
2012 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 

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designed to record all observations and other data pertinent to the investigation on each individual 
treated with the investigational agent or employed as a control in the investigation.” Among many other 
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 
• 
Participant-completed Vaccine Report Card.  
 
12.4 
Data and Safety Monitoring Plan 
 
The 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 
IRB 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 

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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. 
 
12.7 
Cooperative Research and Development Agreement (CRADA)/Clinical Trials Agreement (CTA) 
 
A CRADA/CTA agreement is not needed as, the contact between DCP and Mayo along with the Mayo 
subcontract with the University of Pittsburgh delineate each party’s’ responsibilities. 
 
 
13.  STATISTICAL CONSIDERATIONS 
 
13.1  Study Design/Description 
 
This is a randomized Phase II double blind placebo controlled trial designed to assess the effects of the 
MUC1-1 peptide with poly-ICLC adjuvant vs. placebo.  There will be 3 “Parts” to the study to allow 
periodic monitoring and the opportunity to evaluate whether to proceed after each part.  They key 
endpoints from each part are listed below:   
 
Part I: The ratio of the week 12 to week 0 IgG levels will be calculated and compared between the MUC1 
vaccine and placebo (primary endpoint, see 13.4).   
Part II:  Assessment of the booster response at week 55 vs. week 52 (T55/T52) for the vaccine as 
compared to placebo (key secondary endpoint, see 13.5) 
Part III:  Comparison of the adenoma recurrence rate from surveillance exams occurring at least one 
year and up to three years after Week 0 vaccine administration – MUC1 peptide versus placebo.  All 
patients will be followed for this endpoint (key secondary endpoint, see 13.5)  
 
In addition to these key powered endpoints for the 3 different parts, we will also assess the following 
additional secondary endpoints: 
• 
Comparison of adverse events between the MUC1 vaccine and placebo during part 1 and 2 (13.7). 
• 
To assess patient –reported vaccine-related side effects from the Vaccine Report Card. 
• 
Comparison of the proportion of patients with at least a 2-fold increase in the IgG ratio between the 
2 arms at 12 weeks (13.5).  
• 
Comparison of the adenoma recurrence rates between MUC1 and placebo by excluding the 
following types of adenomas. These adenomas are excluded since they may represent missed or 
residual adenomas from the baseline exam. These analyses are exploratory. 
o Participants with adenomas ≤ 5 mm, 
o Participants with adenomatous tissue which may represent residual adenoma at the site of the 
previous advanced adenoma, 
o Participants with adenomatous tissue detected in the same segment of the bowel as the 
previous advanced adenoma. 
• 
Assessment of participant-reported injection site reaction events from the Vaccine Report Card 
(Appendix E). 
 
 
 
 

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In addition, we will assess the following translational endpoints (see 13.10): 
• 
To compare the anti-MUC1 antibody titer at the time of surveillance colonoscopy for the purpose of 
evaluating the anti-MUC1 antibody response in relation to adenoma recurrence. Since surveillance 
colonoscopy is generally at 3 years after an advanced adenoma, this titer will typically be obtained 
at approximately week 156. 
• 
To evaluate MUC1 expression on baseline advanced adenomas and on recurrent adenomas 
detected at surveillance colonoscopy. Based on current knowledge of MUC1 expression and 
function in tumor cells, MUC1 negative adenomas are not expected to grow as immune escape 
variants, but this has never been tested before and the trial will provide an appropriate setting to 
study this issue.   
• 
To evaluate levels of circulating myeloid derived suppressor cells (MDSC) in the vaccinated and the 
placebo group and correlate with anti-MUC1 antibody levels and adenoma recurrence. 
• 
To establish a biospecimen repository archive including live cells, plasma, and germline DNA for 
future immunologic and other assays, for testing not currently accommodated within the budget of 
this trial. 
 
There are limited Quality of Life (QOL) data on participants who participate in chemoprevention trials 
and we intend to create a databank of QOL information by administering the “Was It Worth It” (WIWI) 
questionnaire at trial completion across multiple trials. We will seek to evaluate participant perception 
of their experience in trial participation once we have a reasonable amount of information (large 
enough sample size). Since participants who participate in these chemoprevention trials are high risk but 
otherwise healthy, the WIWI tool would help answer simple questions about participants’ assessment of 
whether or not participation in this trial was “worth it.”  
 
In addition to the WIWI Questionnaire, participants will be asked to complete a pre-vaccine 
questionnaire at baseline (prior to the Week 0 injection) and a post-vaccine questionnaires at Week 53 
(after the Week 53 booster injection) and approximately Week 156.  These questionnaires were used in 
the Pilot study of this MUC1 vaccine and are designed to gather information about perceived risk, 
regret, and symptoms.  The original copies of these questionnaires will be placed in the participants’ 
study files.  Copies should be sent electronically to: Lyn Robertson DrPH, RN, MSN, University of 
Pittsburgh; Email: robertsonlk@upmc.edu.  Questions should be forwarded to Dr. Robertson by email or 
telephone: 412-647-8588. 
 
Information from these risk assessments will only be used as supplementary data to explain for any 
potential confounding factors and not for any analytical purposes. 
 
13.2 
Randomization/Stratification  
 
Participants will be randomized in a 1:1 fashion to one of two arms (MUC1 vs. placebo), using a dynamic 
allocation procedure called the Pocock-Simon 42,  which balances the marginal distributions of the 
stratifications factors across the intervention groups and has been shown to be able to accommodate a 
large number of factors (10-20) without difficulty43.  For this study we will use the following stratification 
factors:  number of adenomous polyps removed >=3 vs. < 3 and gender. 
 
 
 

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13.3 
Accrual and Feasibility 
 
The study design requires a total of 120 participants for screening evaluation with approximately 110 
moving forward to randomization (55 total participants per arm) due to anticipated screen failures of 
approximately 8% prior to randomization.  We further expect up to 10% of participants to drop out or 
otherwise become non-evaluable by 1 year; this rate will be reflected in power calculations for parts 1 
and 2. An additional 10% expected drop out or exclusion rate between 1 and 3 years is expected, 
reflected in the power calculations for part 3. We expect to enroll a minimum of 1 participant per month 
for each of the participating CPN sites, for an overall accrual rate of 8 participants s per month.  With 
this accrual rate and with a 3-6 month ramp up for participating organizations, we plan to complete 
accrual in about 18 months.  Accounting for patient follow-up, data entry, and analysis, the part 1 
portion of the study is expected to be completed in about 22 months, followed by an additional 12 
months for part 2 and an additional 24 months for part 3.  The entire study duration is expected to take 
approximately 62 months (5.1 years), if we complete all 3 parts of the study.    
 
13.4 
Primary Objective, Endpoint, Analysis Plan 
 
The primary objective for this study is to compare the ratio of the week 12 to week 0 IgG levels between 
the MUC1 vaccine and placebo.  It is hypothesized that this ratio will be increased in patients treated 
with the MUC1 vaccine as compared to patients receiving the placebo.   Prior data from a pilot study of 
39 patients that were treated with the MUC1 vaccine37 showed a mean IgG ratio of 6.46 with a standard 
deviation of about 10.  Assuming equal standard deviations (i.e. 10) across the MUC1 and placebo 
groups, and assuming up to a 10% drop-out rate by year 1 (presumably less by 12 weeks), retaining at 
least 50 evaluable participants per arm yields at least 86% power to detect an increase in the mean IgG 
ratio from 1 to 6.5 for placebo vs. MUC1 (effect size = 0.55), using a 1-sided t-test with a significance 
level of 0.05. If the data are not normally distributed, we will use the Wilcoxon Rank-Sum test for this 
primary endpoint analysis.  If the vaccine shows a significant increase in the 12-week immune response 
rate as compared to placebo, we will proceed to Part 2.   
 
13.5 
Secondary Objectives, Endpoints, Analysis Plans 
 
As discussed previously, there will be key powered secondary endpoints for this study across all 3 parts.   
 
1)  Immune response at 12 weeks (Part 1):  The key secondary endpoint for Part 1 will compare the 
proportion of patients that have at least a 2-fold increase in the IgG ratio (week 12/week 0) between 
MUC1 and placebo.    Based on the pilot study37, we hypothesize that around 40% of vaccinated 
participants will demonstrate a 2 fold increase in MUC1 titer at week 12 compared to around 10% for 
the placebo arm.  Assuming a drop-out rate of up to 10% by 1 year (presumably less by 12 weeks), 
retaining at least 50 evaluable participants per arm provides 94% power to detect an increase in the 12-
week immune response rate from 10 to 40%, assuming a 2-sided significance level of 0.05 (nQuery 
Advisor 6.01).   
 
2) Booster Response at 1 year (Part 2):   The key secondary endpoint for Part 2 will assess the booster 
response at week 55 vs. week 52 for the vaccine as compared to placebo. Based on the pilot study, we 
expect 75% of week-12 responders will respond with a doubling of MUC1 antibody levels, or about 35% 
of the overall sample.  We expect the 1-year response rate to be around 10% in the placebo group.  Of 
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approximately 100 participants evaluable for this analysis (50/arm).  With 50 evaluable participants per 
arm, we would have 92% power to detect an increase in the 1-year immune response rate from 10 to 
35%, assuming a 1-sided significance level of 0.05 (nQuery Advisor 6.01).  We will also compare the 
actual IgG ratio values between the 2 treatment arms as well.   If the booster vaccine shows a significant 
increase in the 1-year immune response as compared to placebo and a response rate that exceeds 15%, 
we can proceed to Part III.       
 
3)  Adenoma recurrence rate at 3 years (Part 3):  Part 3 will evaluate the adenoma recurrence rate at 
least one year and up to 3 years. The adenoma recurrence rate at 3 years in participants with an 
adenoma is generally around 40-50% 33.  Assuming an additional 10% drop out rate between years 1 and 
3, we will have 90 participants (45/arm) evaluable for this endpoint, which will provide >80% power for 
the different effect sizes shown in the table below (1-sided alpha = 0.05).  
 
# Evaluable  
Effect Size 
(delta) 
Power 
1-sided alpha 
90 (45/arm) 
50 vs. 25% 
79% 
0.05 
90 (45/arm) 
45 vs. 20% 
82% 
0.05 
90 (45/arm) 
40 vs. 15% 
85% 
0.05 
 
4)  As an exploratory analysis, we will also evaluate the adenoma recurrence rate from surveillance 
exams occurring at least 1 year and up to 3 years after Week 0 vaccine administration between MUC1 
and placebo by excluding adenomas ≤ 5 mm, adenomatous tissue that may represent residual adenoma 
at the site of a previous adenoma, and adenomatous tissue detected in the same segment of the bowel 
as the previous advanced adenoma. These adenomas are excluded since they may represent missed or 
residual adenomas from the baseline exam. These analyses are exploratory. 
 
5) Participant-reported injection site reaction information will be collected by use of a participant-
completed Vaccine Report Card (Appendix E).  Descriptive statistics will be used to summarize these 
data and compare the data between study arms. 
 
13.6 
Reporting and Exclusions 
 
All randomized participants who are evaluated at week 0 and week 12 and have IgG values from those 
time points will be evaluable for the primary endpoint of this study using the intent-to-treat principle.  
We plan to over randomize assuming 10% drop out within 1 year 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. 
 
13.7 
Evaluation of Toxicity (secondary endpoint) 
 
All participants will be evaluable for adverse events (AEs) from the time of their first dose of MUC1 or 
Placebo during parts 1 and 2 of the study. To evaluate the AE profiles associated with each arm, the 
maximum grade for each type of adverse event will be recorded for each participant and frequency 
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(overall and by arm) will be tabulated and summarized across all grades.  Grade 3+ 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 within and 
across the MUC1 and placebo arms. 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. 
 
In addition, we will assess patient reported vaccine-related side effects from the Vaccine Report Card as 
an exploratory analysis.  We will summarize the results descriptively and compare the results between 
the 2 arms.   
 
13.7.1 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 during the first 2 parts of the study (i.e. first 57 weeks): 
 
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 randomized participants who are evaluated at week 0 and week 12 and have IgG values from those 
timepoints will be evaluable for the primary endpoint of this study using the intent-to-treat principle.  
All conclusions regarding efficacy will be based on all participants who completed both week 0 and week 
12 and have IgG values from those timepoints as well.  Subanalyses may be performed on the subsets of 
participants, excluding those for whom major protocol deviations have been identified (e.g., early death 
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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 Analyses 
 
Part I:  The Part 1 primary endpoint analysis will be the first interim analysis.   If the MUC1 vaccine is 
shown to significantly increase the IgG ratio as compared to placebo, we will move into the Part 2 
portion of the study.  This is defined in detail in Section 13.4.   
 
Part II:  If the booster vaccine shows a significant increase in the 1-year immune response as compared 
to placebo and the response rate exceeds 15%, we can proceed to Part III.        
 
Study enrollment and implementation will not be halted for these analyses unless the results indicate 
that the study should not proceed to the next Part. 
 
13.10 Ancillary Studies 
 
We will assess the following translational endpoints for this study. 
• 
To compare the anti-MUC1 antibody titer at the time of surveillance colonoscopy to evaluate the 
anti-MUC1 antibody response in relation to adenoma recurrence. Since surveillance colonoscopy is 
generally at 3 years after an advanced adenoma, this titer will typically be obtained at approximately 
week 156. 
• 
To evaluate MUC1 expression on baseline advanced adenomas and on recurrent adenomas 
detected at surveillance colonoscopy. Based on current knowledge of MUC1 expression and 
function in tumor cells, MUC1 negative adenomas are not expected to grow as immune escape 
variants, but this has never been tested before and the trial will provide an appropriate setting to 
study this issue.   
• 
To evaluate levels of circulating myeloid derived suppressor cells (MDSC) in the vaccinated and the 
placebo group and correlate with anti-MUC1 antibody levels and adenoma recurrence. 
• 
To establish a biospecimen repository archive including live cells, plasma, and germline DNA for 
future immunologic and other assays, for testing not currently accommodated within the budget of 
this trial. 
 
Analysis of these translational endpoints: 
Laboratory measures will be correlated with participant outcome (i.e., adverse events, IgG levels, 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 within each arm 
using Wilcoxon signed rank tests, and paired sample t-tests.  Comparisons between MUC1 and placebo 
will be performed using a two-sample t-test or Wilcoxon rank sum test, as appropriate. 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. 
 

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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 “Protection of Human Research Subjects” for all study personnel 
listed on the FDA Form 1572 and Delegation of Tasks form for the Lead Organization and all Participating 
Organizations. 
 
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 
Institutional Review Board 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 
IRB. 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 IRB prior to implementation 
 
 
 
 

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14.4 
Informed Consent 
 
All potential study participants will be given a copy of the IRB-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 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.  
 
Prior to study initiation, the informed consent document must be reviewed and approved by NCI, DCP, 
the Consortium Lead Organization, and the IRB at each Organization at which the protocol will be 
implemented. Any subsequent changes to the informed consent must be approved by NCI, DCP, the 
Consortium Lead Organization’s IRB, and then submitted to each organization’s IRB for approval 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 the DCP Regulatory Contractor: 
 
 
Paper Document/CD-ROM Submissions: 
 
Regulatory Affairs Department 
 
CCS Associates 
 
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 the DCP 
Regulatory Contractor. 
 
14.6 
Other 
 
This trial will be conducted in compliance with the protocol, Good Clinical Practice (GCP), and the 
applicable regulatory requirements. 
 
 

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15. 
FINANCING, EXPENSES, AND/OR INSURANCE 
 
No expenses will be incurred by the study participant and/or their insurance carrier.  This does not 
include any injuries or illnesses the participant may have related to their participation on the study.  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 may be provided remuneration for their 
participation in the study, at the discretion of the local Institutional Review Board. 
 
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Hattrup CL, Gendler SJ. Structure and function of the cell surface (tethered) mucins. [Review] 
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20. 
Tang CK, Katsara M, Apostolopoulos V. Strategies used for MUC1 immunotherapy: human 
clinical studies. [Review] [108 refs]. Expert Review of Vaccines 2008;7:963-975. 
21. 
Cheever MA, Allison JP, Ferris AS, et al. The prioritization of cancer antigens: a national cancer 
institute pilot project for the acceleration of translational research. Clinical Cancer Research 
2009;15:5323-37. 
22. 
Ramanathan RK, Lee KM, McKolanis J, et al. Phase I study of a MUC1 vaccine composed of 
different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced 
pancreatic cancer. Cancer Immunology, Immunotherapy 2005;54:254-264. 
23. 
Kimura T, Finn OJ. MUC1 immunotherapy is here to stay. Expert Opinion on Biological Therapy 
2013;13:35-49. 
24. 
Fontenot JD, Tjandra N, Bu D, et al. Biophysical characterization of one-, two-, and three-tandem 
repeats of human mucin (muc-1) protein core. Cancer Research 1993;53:5386-94. 
25. 
Kotera Y, Fontenot JD, Pecher G, et al. Humoral immunity against a tandem repeat epitope of 
human mucin MUC-1 in sera from breast, pancreatic, and colon cancer patients. Cancer 
Research 1994;54:2856-60. 
26. 
Levy H, Bever, C. Immune modulating effects of PICLC in mice, monkeys, and man. In: Carraher 
C, Foster, V., ed. Applied Bioactive Polymers. New York: Plenum, 1988. 
27. 
Geiss G, Jin G, Guo J, et al. A comprehensive view of regulation of gene expression by double-
stranded RNA-mediated cell signaling. J Biol Chem 2001;276:30178-82. 
28. 
Salazar AM, Engel WK, Levy HB. Poly ICLC in the treatment of postinfectious demyelinating 
encephalomyelitis. Arch Neurol 1981;38:382-3. 
29. 
Ewel CH, Urba WJ, Kopp WC, et al. Polyinosinic-polycytidylic acid complexed with poly-L-lysine 
and carboxymethylcellulose in combination with interleukin 2 in patients with cancer: clinical 
and immunological effects. Cancer Res 1992;52:3005-10. 
30. 
Salazar AM, Levy HB, Ondra S, et al. Long-term treatment of malignant gliomas with 
intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and 
carboxymethylcellulose: an open pilot study. Neurosurgery 1996;38:1096-103; discussion 1103-
4. 
31. 
Butowski N, Lamborn KR, Lee BL, et al. A North American brain tumor consortium phase II study 
of poly-ICLC for adult patients with recurrent anaplastic gliomas. Journal of Neuro-Oncology 
2009;91:183-9. 
32. 
Butowski N, Chang SM, Junck L, et al. A phase II clinical trial of poly-ICLC with radiation for adult 
patients with newly diagnosed supratentorial glioblastoma: a North American Brain Tumor 
Consortium (NABTC01-05). Journal of Neuro-Oncology 2009;91:175-82. 
33. 
Rosenfeld MR, Chamberlain MC, Grossman SA, et al. A multi-institution phase II study of poly-
ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly 
diagnosed glioblastoma. Neuro-Oncology 2010;12:1071-7. 
34. 
Kimura T, McKolanis JR, Dzubinski LA, et al. MUC1 Vaccine for Individuals with Advanced 
Adenoma of the Colon: A Cancer Immunoprevention Feasibility Study. Cancer Prevention 
Research 2013;6:18-26. 
35. 
Akporiaye ET, Bradley-Dunlop D, Gendler SJ, et al. Characterization of the MUC1.Tg/MIN 

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transgenic mouse as a model for studying antigen-specific immunotherapy of adenomas. 
Vaccine 2007;25:6965-6974. 
36. 
Beatty PL, Narayanan S, Gariepy J, et al. Vaccine against MUC1 antigen expressed in 
inflammatory bowel disease and cancer lessens colonic inflammation and prevents progression 
to colitis-associated colon cancer. Cancer Prevention Research 2010;3:438-446. 
37. 
Beatty P, Ranganathan S, Finn OJ. Prevention of Colitis-associated colon cancer using a vaccine 
to target abnormal expression of MUC1 tumor antigen Oncoimmulology 2012;1:263-270. 
38. 
Martinez ME, Baron JA, Lieberman DA, et al. A pooled analysis of advanced colorectal neoplasia 
diagnoses after colonoscopic polypectomy. Gastroenterology 2009;136:832-841. 
39. 
Saini SD, Kim HM, Schoenfeld P. Incidence of advanced adenomas at surveillance colonoscopy in 
patients with a personal history of colon adenomas: a meta-analysis and systematic review. 
[Review] [35 refs]. Gastrointestinal Endoscopy 2006;64:614-626. 
40. 
Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid 
adenomas [see comments]. New England Journal of Medicine 1992;326:658-662. 
41. 
Silk AW, Schoen RE, Potter DM, et al. Humoral immune response to abnormal MUC1 in subjects 
with colorectal adenoma and cancer. Molecular Immunology 2009;47:52-56. 
42.         Pocock, S.L., and Simon, R. Sequential treatment assignment with balancing for prognostic 
              factors in the controlled clinical trial. Biometrics, 31: 103-15, 1975. 
43.        Therneau TM. How many stratification factors are “too many” to use in a randomization plan? 
              Controlled Clin Trials 14 (1993), pp. 98-108. 
 

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Study Title: MAY2013-01-01 “Randomized, Double-Blind, Placebo-Controlled Trial 
of MUC1 Vaccine in Patients with Newly Diagnosed Advanced Adenomas” 
 
Short Title:  MUC1 Vaccine Trial for the Prevention of Polyps and Adenomas 
 
Instructions to Participating Sites:  This is a template designed to provide you with the information you 
will need for your institution’s informed consent document.  Please paste applicable information into 
the format required by your Institutional Review Board (IRB). Text in bold, other than the section 
headings, is required. You are welcome to add any text required by your IRB and/or institution.  Please 
submit your draft consent document to the CPN Operations Office for review prior to submission to 
your IRB. Please remove these instructions (blue text) prior to submission. 
 
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. 
 
You are being invited to take part in this research study because you have a history of advanced 
adenomatous polyps. Adenomatous polyps are growths in your colon that may turn into cancer over 
time. 
 
Why is this study being done? 
 
The MUC1/poly-ICLC vaccine is being tested in persons with a history of advanced adenomatous polyps, 
which are growths that may develop into colorectal cancer.  The primary purpose of this study is to 
compare the safety and effects of the MUC1/poly-ICLC vaccine with placebo and to see if the vaccine 
can prevent the recurrence of adenomatous polyps. 
 
How many people will take part in the study?  
 
About 120 people will be screened at 8 different medical centers around the United States and in Puerto 
Rico.  We estimate that about 110 people will take part in the study. 
 
What will happen if I take part in this research study?  
 
Before you begin the study, you will need to have the following exams or procedures to find out if you 
can be in the study. These procedures are not part of your standard medical care. 
 
 
 
 
 

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Before the study 
 
Procedures to determine if you are eligible to take part in a research study are called “screening or 
baseline procedures.”   For this research study, the screening/baseline procedures, which may take up 
to 2 hours, include: 
 
• 
You will be asked to read, understand, and sign this consent form. 
• 
You will be asked to provide information about your past medical history, you will undergo a 
physical examination (including pulse rate, temperature, blood pressure, height, and weight), and 
you will be asked about current symptoms or illnesses. 
• 
You will be asked about drug allergies and all medications you are taking. 
• 
Approximately, 80 cc (4 tablespoons) of blood will be collected from a vein in your arm for eligibility 
and research.  Blood will also be drawn and tested several times during study to measure changes 
that might have been caused by the injection.  
• 
A blood or urine pregnancy test, if you are woman able to become pregnant 
• 
Pregnant women, women who are currently breast-feeding, and women considering a pregnancy 
will not be allowed to participate.  
• 
Men considering fathering a child are also not allowed to participate.  
• 
All procedures will be performed as an outpatient  
 
During the study 
 
If you are eligible for the study and wish to participate you will be “randomized” into one of two study 
groups.  Randomization means that a computer program will be used to place you into one of the two 
study groups by chance. Neither you nor your doctor can choose the group you will be in and neither 
you nor your doctor will know which group you’ve been assigned to.  One group will be injected with the 
MUC1/poly-ICLC vaccine on 4 occasions: Weeks 0, 2, 10, and Week 53. The other group will be injected 
with a similar looking injection called a placebo.  The placebo injection will contain salt water.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Instruction to Participating Sites:  If your IRB/REB requires it or if you believe it would be helpful for 
your study participants, you may create a study calendar or chart. 
 
After the screening visit and placement into one of the study groups, you will be asked to return to the 
outpatient study site for the following schedule:  
 
Week 0 
• 
You will be asked to complete some brief questionnaires. These will take 15-30 minutes. 
• 
You will receive 0.30 cc (1/20 of a teaspoon) of MUC1/poly-ICLC study vaccine or 0.30cc (1/20 of a 
teaspoon) of salt water. The injection will be administered subcutaneously (SQ) (under the skin) in 
the upper thigh with a thin, tiny needle (like the one used for a tuberculosis test). The site of 
You agree to take 
part in the study 
Randomization 
(A computer will 
randomly put you 
into a study group) 
Group 1: Active vaccine injection 
Group 2: Salt water injection 

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injection will remain the same for all injections. If you are a woman able to have a child, a pregnancy 
test will be performed prior to each study injection.  
• 
You will be given a Vaccine Report Card along with instruction for completing it and reporting any 
reaction to the study injections.   
 
Week 2 and week 10 
• 
Your heart rate, temperature, and blood pressure will be checked, and medications will be reviewed 
and recorded.  
• 
You will be asked questions about any side effects you may have experienced after your study 
injection. Your first Vaccine Report Card will be collected, and a new one will be provided. 
• 
Approximately, 80 cc (4 tablespoons) of blood will be collected from a vein in your arm and tested to 
see if there are any changes that might have been caused by the study injection.  You will also be 
given the results of the blood tests used to monitor your health, performed at your previous visit. 
• 
If you are a woman able to have a child, a pregnancy test will be performed. 
• 
The vaccine or placebo injection will be administered subcutaneously (SQ) in the same upper thigh 
after a review of the routine laboratory testing results.  
 
Week 12  
• 
You will be asked questions about any medications you may be taking and any side effects you may 
have experienced after your study injection. 
• 
Your Week 10 Vaccine Report Card will be collected. 
• 
Approximately, 80 cc (4 tablespoons) of blood will be collected from a vein in your arm and tested to 
measure changes that might have been caused by the study injection.  
 
Week 52 
• 
You will undergo a medical history, physical examination (including heart rate, temperature, blood 
pressure, height, and weight), review of previous test results, and current symptoms or illnesses 
• 
You will be asked about drug allergies and all medications you are taking. Approximately, 80 cc (4 
tablespoons) of blood will be collected from a vein in your arm and tested to measure changes that 
might have been caused by the study injection.  
 
Booster vaccine injection:  Week 53 
• 
If you are a woman able to have a child, a pregnancy test will be performed prior to study injection. 
• 
You will be given another Vaccine Report Card to record any reactions to the booster injection. 
• 
You will be asked to complete some brief questionnaires very similar to the one you completed at 
the beginning of the study.  
• 
The fourth and last study injection will be administered. 
 
Week 55 (about 2 weeks after booster vaccine) 
• 
Your heart rate, temperature, and blood pressure will be checked, and any medications will be 
reviewed and recorded.  
• 
You will be provided with the results of the blood tests done at your previous visit. 
• 
You will be asked questions about any side effects you may have experienced after your study 
injection, and your Vaccine Report Card will be collected. 
• 
You will be asked to complete a “Was It Worth It” Questionnaire.  

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• 
Approximately, 80 cc (4 tablespoons) of blood will be collected from a vein in your arm and tested to 
measure changes that might have been caused by the study injection.  
 
Week 4, 6, 16, 28, 40, 57 
• 
You will be contacted by phone between clinic visits by a research coordinator.  At each telephone 
interview, you will be asked questions about any side effects you may be having, any medications 
you may be taking, and your overall health.  
 
Phone calls approximately every 6 months following booster injection   
Patients with advanced adenomas typically undergo repeat colonoscopy 3 years after initial detection of 
an advanced adenoma.  However, clinicians performing colonoscopy may bring participants back earlier 
than the typical 3-year interval.  You will be contacted by phone about every 6 months after the booster 
injection at week 53 to monitor your health, ask about any medications you are taking, and to check on 
any planned colonoscopy exams.  Please notify study personnel if and when a colonoscopy exam is 
scheduled.   
 
At the time of your next colonoscopy (approximately 12-36 months, possibly longer, after beginning the 
study) 
• 
Your heart rate, temperature, and blood pressure will be checked and any medications used will be 
reviewed and recorded.  
• 
Approximately, 80 cc (4 tablespoons) of blood will be collected from a vein in your arm and tested to 
measure any changes that might have been caused by the study injection.  
• 
A medical release to acquire the colonoscopy report and pathology findings will be obtained, if 
needed.  
• 
A medical release to obtain tissue specimens from polyps found at subsequent colonoscopy (if any) 
will be requested, if needed, from the pathology department where the tissue blocks reside. These 
tissue blocks will be used for research study. 
• 
You will be asked to complete one final questionnaire about your experience in this study. 
 
After Study Follow Up 
 
Study personnel may contact you in the future to see if you are interested in participating in any 
additional research studies.   
 
How long will I be in the study? 
 
You will be in the study through the time of your next colonoscopy depending upon when your next 
colonoscopy occurs.  The timing of your next colonoscopy will be up to your regular doctor.  It may be 
three years, but it could be more or less than that.  Even if you do not finish the study, your doctor will 
continue to watch you for side effects. 
 
Can I stop being in the study? 
 
Yes. You can decide to withdraw at any time.  Tell the study doctor if you are thinking about stopping or 
decide to stop.  The investigators will discuss withdrawal from the study with you.    
 

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The study doctor may stop you from taking part in this study at any time if he/she believes stopping is in 
your best interest; if you do not follow the study rules; or if the study itself is stopped.  
 
What are the possible risks, side effects, and discomforts of this research study? 
 
You may or may not have side effects while on the study. Everyone taking part in the study will be 
watched carefully for  side effects. However, doctors don’t know all the side effects that may happen. 
Side effects may be mild or very serious. Your health care team may give you medicines to help lessen 
side effects. In some cases, side effects can be serious, long lasting, or may never go away.  
 
You will be asked to keep track of any symptoms and possible side effects using a Symptom Diary and a 
Vaccine Report Card.  The study team will provide instructions on how to complete these, and they will 
be reviewed at each study visit.  
 
Most of the information in the below table is based on a variety of previous studies that were similar to 
this study in some ways but different in some important ways that may have led to different side 
effects.  In the study that was most similar to this study, no autoimmune or serious adverse reactions 
were identified. 
 
Common, Some May Be Serious 
In 100 people who receive the injection, more than 20 may have: 
• 
Redness at injection site (erythema) 
• 
Pain/soreness at injection site 
• 
Flu-like symptoms, which may include fever, chills, headache, fatigue, muscle pain, and joint pain 
• 
Night sweats 
• 
Loss of appetite 
• 
Low albumin blood test result (a type of protein in the blood) 
 
The redness and soreness generally resolve within a few days to a week. The flu-like symptoms generally 
resolve within 12-24 hours.   Acetaminophen (Tylenol®) generally helps with these symptoms if they 
occur.  
 
Occasional, Some May Be Serious 
In 100 people who receive the injection, 4 to 20 may have: 
• Low white blood cell count (cells that fight infections) 
• Low platelet count (cells that help the blood clot in order to stop bleeding) 
• Anemia (which may cause tiredness, or may require blood transfusion) 
• Abnormal liver function test results 
 
Rare, Some May Be Serious 
In 100 people who receive the injection, 3 or fewer may have: 
• 
Hives, shortness of breath, or an allergic reaction that is life-threatening 
• 
Immune reaction to his or her own tissue (autoimmune diseases) or if present, may be made 
worse.  
 
 

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Risks of the blood tests 
 
Bruising, soreness, or rarely, infection may occur as a result of the needle sticks to obtain blood from 
your vein.  
 
Risks of the questionnaires 
 
There are some questions on the study questionnaires that may request sensitive information or make 
you uncomfortable. You are welcome to skip any questions that you do not wish to answer. 
 
Reproductive risks 
   
You should not become pregnant or father a baby while on this study because we do not know the 
effect that the drugs in this study may have on an unborn baby.  Women should not breastfeed a baby 
while on this study.  You should use adequate birth control methods while on this study if you are at risk 
for becoming pregnant or impregnating 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. 
 
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? 
 
There may or may not be direct medical benefit to you.  At this time, it is not known whether or not the 
MUC1/poly-ICLC vaccine can prevent or delay adenomatous polyp recurrence.   
 
 
 
 
 
 
 
 
 
 
What other choices do I have 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: 
1. You may choose to have the usual approach which is periodic colonoscopy to monitor for polyps 
without being in a study. Please remember that participation in this research study does not 
take the place of the colonoscopy.  
2. You may choose to take part in a different study, if one is available. 
 
If I agree to take part in this research study, will I be told of any new risks that may be found during 
the course of this study? 
 
You will be promptly notified if, during the conduct of this research study, any new information develops 
which may cause you to change your mind about continuing to participate. 
 
Will my insurance provider or I be charged for the costs of any procedures performed as part of this 
research study? 
 

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Neither you, nor your insurance provider, will be charged for the costs of procedures that are part of the 
research study. The sponsor will pay all costs associated with the research study.  You or your insurer 
will be billed for any routine, standard care services not connected to the research study.  You will be 
responsible for any usual co pays, insurance, or deductibles. Follow up colonoscopy exams are part of 
your standard clinical care. They are not part of the study, and the study does not pay for these tests.  
Before you take part in this study, you should contact your insurer to find out if the cost of these tests 
will be covered. You will have to pay for any costs not covered by your insurance.   
 
For more information on clinical trials and insurance coverage, you can visit the National Cancer 
Institute’s Web site at:  http://www.cancer.gov/clinicaltrials/learning/insurance-coverage 
 
You can print a copy of the “Clinical Trials and Insurance Coverage” information from this Web site. 
 
Are there any costs or payments? 
 
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.   
 
Note to participating organizations:  You may provide whatever payments to the participants are 
allowed by your Institutional Review Board.  Payments to each participant may not exceed a total of 
$400. You are allowed to break this into smaller payments for each visit and, if appropriate, provide that 
detail in this section.  
 
Will my medical information be kept private?  
 
Your privacy is very important to us and we will make every effort to protect it. Your information may be 
given out if required by law. For example, certain states require doctors to report to health boards if 
they find a disease like tuberculosis. However, we will do our best to make sure that any information 
that is released will not be able to identify you. There are organizations that may inspect your records. 
These organizations are required to make sure your information is kept private. Some of these 
organizations are: 
• 
The National Cancer Institute (NCI) and other government agencies, such as the Food and Drug 
Administration (FDA), involved in keeping research safe for people. 
• 
Regulatory agencies within and outside the United States. 
• 
The Institutional Review Board. 
 
The National Cancer Institute will obtain information from this clinical trial under data collection 
authority Title 42 U.S.C. 285. 
 
What happens if I am injured as a result of taking 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. 
 
What are my rights if I take part in this study? 
 
Taking part in this study is your choice.  You may choose either to take part or not to take part in the 
study.  If you decide to take part in this study, you may leave the study at any time.   No matter what 
decision you make, there will be no penalty to you and you will not lose any of your regular benefits.  
Leaving the study will not affect your medical care.  You can still get your medical care from the 
institution conducting the study.    
 
We will tell you about new information or changes in the study that may affect your health or your 
willingness to continue in the study.  In the case of injury resulting from this study, you do not lose any 
of your legal rights to seek payment by signing this form or release the institution from liability for 
negligence. 
 
Please note:  This section of the informed consent document is about additional research studies that 
are being done with people taking part in the main study.   You may take part in these additional 
studies if you want to.  You can still be a part of the main study even if you say “no” to taking part in 
any of these additional studies. 
 
 
About Using Your Blood and Tissue for Research  
 
We are drawing your blood and requesting specimens from your colonoscopy exams as part of the 
study.   We would like to keep the left over blood and tissue for future research. If you agree, this blood 
and tissue will be kept and may be used in research to learn more about cancer and other diseases.  
 
Your blood and tissue may be helpful for research whether or not you have cancer. The research that 
may be done with your blood and tissue is not designed specifically to help you. It might help people 
who have cancer and other diseases in the future.  
 
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. 
  
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 and supported by the 
National Cancer Institute. 
  

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Your samples and some related information may be stored in the Biobank, along with samples and 
information from other people who take part. The samples will be kept until they are used up. 
  
Qualified researchers can submit a request to use the materials stored in the Biobank. A research 
committee at the Cancer Prevention Network and the National Cancer Institute 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. 
  
Neither you nor your study doctor will be notified if/when research is conducted using your samples. 
  
Some of your genetic and health information may be placed in central databases that may be public, 
along with information from many other people. Information that could directly identify you will not be 
included. 
 
Things For You To Think About  
 
The choice to let us keep the leftover blood and tissue for future research is up to you. No matter what 
you decide to do, it will not affect your care.  
 
What If I Change My Mind? 
 
If you decide now that your blood and tissue can be kept for research, you can change your mind at any 
time.   If you change your mind, please contact <Participating Organization Investigator > at <Institution 
Address> and let them know that you do not want your blood and tissue to be used. Then any blood and 
tissue that remain will no longer be used for research.  Samples or related information that have already 
been given or used by researchers will not be returned. 
 
 
Benefits  
 
 
The benefits of research using blood and tissue include learning more about what causes cancer and 
other diseases, how to prevent them, and how to treat them.   You may not benefit from taking part. 
 
Risks  
 
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.  
 
Here are just a few of the steps the researchers will take to protect your privacy: 

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1. When your samples are 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.  
2. The list that links the unique code to your name will be kept separate from your sample and 
health information. Any Biobank and Cancer Prevention Network staff with access to the list 
must sign an agreement to keep your identity confidential. 
3. Researchers to whom the Cancer Prevention Network 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. 
 
Making Your Choice  
 
Please read each sentence below and think about your choice. After reading each sentence, circle "Yes" 
or "No" and initial each line. If you have any questions, please talk to your doctor or nurse, or call our 
research review board at the phone number provided.  No matter what you decide to do, it will not 
affect your care.  
 
1. My blood and tissue may be collected and stored for future use in research to learn about, prevent, or 
treat cancer.  
 
 
 
 
Yes 
 
No 
 
Initials_________  
 
 
2. My blood and tissue may be collected and stored  for future  use in research to learn about, prevent 
or treat other health problems (for example: Barrett’s esophagus, causes of diabetes, Alzheimer's 
disease, or heart disease).  
 
 
 
Yes  
 
No  
 
Initials_________  
 
3. My blood and/or tissue may be sent to researchers at outside institutions. 
 
Yes  
 
No  
 
Initials_________  
 
4. My study doctor or someone from the Cancer Prevention Network may contact me in the future to 
ask me to participate in future clinical trials.  
 
 
 
Yes  
 
No  
 
Initials_________ 
 
What If I Have More Questions? 
 
You can talk to your study doctor about any questions or concerns you have about this study.  Contact 
your study doctor __________________ <name> at __________________ <telephone number>. 
 

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For questions about your rights while taking part in this study, call the ________________________ 
<name of institution> Institutional Review Board (a group of people who review the research in order to 
protect your rights) at __________________ <telephone number>.  [Note to Local Investigator: Contact 
information for participant representatives or other individuals in a local institution who are not on the 
IRB or research team but take calls regarding clinical trial questions may be listed here.]    
 
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.  This website will not 
include information that can identify you. At most, the website will include a summary of the results. 
You can search this website at any time. 
 
[Note to Informed Consent Authors: the above paragraph (bold text) complies with the new FDA 
regulation found at 21 CFR 50.25(c) and must be included verbatim in all informed consent documents. 
The text in this paragraph cannot be revised.] 
 
You will get a copy of this form. If you want more information about this study, please ask the study 
doctor. 
 
 
 
 
 
Signature 
 
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 ________________________________ 
 
Date _____________________________________ 
     

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APPENDIX A 
 
Performance Status Criteria 
 
 
ECOG Performance Status Scale 
 
 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity. Fully active, able to carry 
on all pre-disease performance without 
restriction. 
100 
Normal, no complaints, no evidence of 
disease. 
90 
Able to carry on normal activity; minor 
signs or symptoms of disease. 
1 
Symptoms, but ambulatory. Restricted in 
physically strenuous activity, but 
ambulatory and able to carry out work of 
a light or sedentary nature (e.g., light 
housework, office work). 
80 
Normal activity with effort; some signs 
or symptoms of disease. 
70 
Cares for self, unable to carry on 
normal activity or to do active work. 
2 
In bed <50% of the time. Ambulatory and 
capable of all self-care, but unable to 
carry out any work activities. Up and 
about more than 50% of waking hours. 
60 
Requires occasional assistance, but is 
able to care for most of his/her needs. 
50 
Requires considerable assistance and 
frequent medical care. 
3 
In bed >50% of the time. Capable of only 
limited self-care, confined to bed or chair 
more than 50% of waking hours. 
40 
Disabled, requires special care and 
assistance. 
30 
Severely disabled, hospitalization 
indicated. Death not imminent. 
4 
100% bedridden. Completely disabled. 
Cannot carry on any self-care. Totally 
confined to bed or chair. 
20 
Very sick, hospitalization indicated. 
Death not imminent. 
10 
Moribund, fatal processes progressing 
rapidly. 
5 
Dead. 
0 
Dead. 
 
 
 
 
 
 

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APPENDIX B 
 
Recruitment and Retention Plan Template 
 
Instructions 
NCI, DCP requires a site and study-specific recruitment, retention, and adherence (RRA) plan for each 
cancer chemoprevention study.  Each participating organization should tailor the study RRA plan 
template to meet the needs at their local site.  The below RRA plan outline is intended as a tool to assist 
site investigators and recruitment coordinators in the RRA planning process.  
 
Black/Bold font indicates required language 
 
Instructions for specific information Participating Organizations should insert into each section are in 
blue italics.  These can be deleted when the site-specific RRA plan is complete. When complete, please 
submit your RRA Plan to the CPN Operations Office for review. 
 
I.  Pre-initiation phase (Developing the Recruitment, Retention, and Adherence Plan) 
 
A. Determine protocol staff assignments (It may be helpful to specify by job title who on the site team 
will fill each of the roles described below) 
1. The site recruitment coordinator, who may be the study coordinator, will have primary 
responsibility for coordinating all aspects of recruitment for this study, including but not limited 
to, reviewing databases, medical records, and previous studies’ participants lists for potentially 
eligible study participants of both genders, all races, and all ethnic groups; contacting these 
individuals to assess interest and initial eligibility (in whatever manner is most appropriate for 
the study and the institution); setting up appointments for screening and informed consent 
(including checking investigators’ schedules for appointment and procedures); and maintaining 
contact with study participants throughout their participation to insure compliance with the 
protocol. 
2. Alternate recruiters and back up personnel will be assigned to assist as needed. 
3. The site PI and site co-investigators (all listed on the study-specific FDA form 1572) will: 
a. Assist in the initial assessment of eligibility 
b. Meet with the site recruitment coordinator regularly to monitor recruitment and accrual 
activity as well as progress of individuals on study 
c. Review the informed consent document with the study participant 
d. Perform all examinations and procedures required per protocol 
e. Determine/confirm eligibility 
f. Provide information and training to other departmental personnel as needed to 
maintain an appropriate level of recruitment and consistent implementation of the 
protocol. 
B. Review protocol design and its impact on recruitment  
1. Evaluate feasibility of sample size: 
a. Availability of target population considering demographics 

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b. Availability of target population considering eligibility criteria  
c. Possible effects of placebo control arm  
d. Possible effects of  participant access to study drug if it is FDA-approved 
e. Possible effects of potential toxicity  
f. Possible effects of complicated entry criteria and burdensome protocol procedures  
2. Calculate availability of eligible participants based on:  
a. Consultation with potential participants  
b. Review of patient lists within each practice.  If appropriate and necessary, contact 
referring physicians for permission to contact their patients. 
c. Review of the literature 
d. Calculate the number of eligible enrolled participants versus number of 
eligible participants who chose not to enroll per site 
e. Estimate accrual rate (# of participants per month) 
3. After a pre-determined period of time,* (if timeframe for achieving overall recruitment goal is 
unrealistic), considerations for protocol modifications include the following: 
a. Broadening eligibility criteria (e.g. time frames for completion of tests and procedures, 
lab values) 
b. Simplifying protocol 
c. Decreasing sample size 
d. Extending recruitment period  
4. Considerations for improving access to this study by women and minorities: 
a. Having multiple sites conduct the study will offer a more diverse population of potential 
participants.  
b. Convert consent form and have translator available for non-English populations 
C. Identify and contact referral sources  
1. Survey potential referral doctors, obtain letter of commitment if possible.  Cultivate working 
relationship with non-oncology specialists who provide care related to the study target organ 
(e.g. Gastroenterologists, Internists, etc.). 
2. Non-physician referrals - Enlist endorsement and cooperation to promote enrollment: 
a. Community centers e.g. Jewish Community Centers (JCC) 
b. Retirement communities 
c. Senior centers 
d. YMCAs, public libraries, etc. 
e. Health clubs 
f. Churches 
g. Local corporations  
h. Alliances with disease specific organizations, such as patient advocacy groups, support 
groups, and charitable organizations 
3. Keep referring physicians updated and engaged using tools such as: 
a. Letters to referring physicians 

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b. Quick fact sheets and cards 
c. Study information posted in physician work areas 
Participating Organizations:  Section D should be left in your site’s plan for informational purposes. 
 
D. Determine and document metrics for evaluation of recruitment and retention performance  
1. Estimated total accrual per site will be 10 per site, with an average of 1-2 participants registered 
per site per month. 
2. Keep site study teams updated and engaged. 
a. Recruitment strategies will be discussed at all the study coordinator teleconferences to 
discuss general effectiveness as well as other approaches. Modified or alternative plans 
will be implemented if recruitment or retention is lagging. 
b. Weekly accrual reports will be generated by the CLO Statistical Programmer Analyst and 
sent to all appropriate study personnel.  These will be summarized and posted on the 
CPN website. 
c. Each site will submit monthly screening and recruitment activity reports, which will be 
summarized and forwarded to DCP study personnel.  These will be reviewed at least 
monthly by the CPN recruitment coordinator and discussed at all study coordinator 
teleconferences. 
d. CLO will keep open communication with study sites, sending out a monthly memo, 
scheduled study coordinator and PI teleconferences, and discussing logistical problems.  
The CLO will be available to assist with resolution of any identified problems.  
3. After initial activation of the study at Mayo and University of Pittsburgh, overall accrual will be 
evaluated quarterly.  If by a predetermined period of time* after initial activation at a given site, 
there have been no participants accrued, the CLO will have a teleconference with the site PI and 
team to discuss issues/obstacles.  A timeframe, i.e. six months, will be determined during which 
the site team must implement its action plan.  If recruitment activity is determined to be 
unsatisfactory at this point, the site will be asked to close to accrual. 
* The time points at which accrual milestones must be met will be determined collaboratively 
between the Study Chair, CLO Personnel, and the DCP Medical Monitor. 
 
Participating Organizations:  Please revise the section E below to describe your site’s specific plans to 
train study team member and provide any pertinent study updates to them.  The Study Coordinator 
Memo mentioned above will be sent to the lead Study Coordinator.  Plans should be described to 
distribute the memo and/or any protocol-related material to all pertinent site study team members. 
 
E. Train staff  
1. Training of participating site personnel by CLO  
a. Site personnel will be provided with the protocol and protocol-related documents in 
accordance with CPN and DCP SOPs 

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b. At or shortly after activation of each site, an orientation webconference will be held to 
provide training in protocol implementation, participant registration, CRF completion, 
etc. 
c. Regular teleconferences will be held with all sites to discuss study implementation, 
questions, and issues. 
d. The CPN website will be used to house the Study Coordinator Workbook, resources 
(such as FAQ lists), and all approved protocol-related materials. 
e. Twice monthly, the CLO will distribute a Study Coordinator Memo to all participating 
sites.  This memo will announce formal distributions of protocols and related materials, 
current accrual, and other pertinent study information. 
2. The staff at each Participating Organization will be informed and trained by the site PI and Study 
Coordinator in accordance with institutional policies and procedures.  This training must be 
documented for the study files, to be reviewed by the CPN Compliance Coordinator during 
monitoring visits. This includes, but is not limited to: 
a. Educating all participating staff regarding the details of protocol implementation and all 
study procedures 
b. Insuring consistent implementation of the protocol 
c. Improving the likelihood that all potentially eligible participants will be identified 
3.  Resources provided by the CLO 
a. Study coordinator and PI teleconference will be held throughout the study every 4-6 
weeks or as needed. 
b. CLO Newsletter will be distributed twice yearly 
c. Recognition of high recruiters and sharing of their specific strategies 
d. Draft recruitment, retention, and adherence materials that can be modified by each 
Participating Organization for review by local IRB prior to use at each Participating 
Organization. These may also include public services announcements, use of social 
media, such as Twitter, and videos to upload to YouTube®. 
e. Buddy system among site study coordinators 
f. Holiday cards with approved study-specific news for distribution to enrolled participants 
(after appropriate approvals are received) 
Participating Organizations:  Please add any additional information necessary to Section F below to 
adequately describe your site’s plans for implementing appropriate informed consent process and 
creating a positive clinical trial experience for your participants. 
 
F.   Each participating site will promote comfortable and pleasant clinic environment/experience in 
accordance with institutional policies and procedures. The following are recommended: 
 
1. Supply driving directions to schedulers.  
2. Coordinate well-organized clinic flow. 
3. Assure user-friendly test scheduling, immunization administration, etc. 

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4. Negotiate (if possible, insist upon) flexible appointment times (i.e., more than one day per 
week). 
5. Plan to allow ample time for participants with the clinical trial staff for the entire informed 
consent process.  
6. Schedule periodic meetings between the clinic coordinator and the protocol staff.  
Participating Organizations:  Please describe in section G any participant compensation or remuneration, 
if applicable.  Please also describe the time and/or funds that will be devoted to participant recruitment, 
retention, and adherence. 
 
G.  Budget:   
The overall budget for this study will involve a standard amount for each participant accrued to the 
study. Partial payments will be made for participants who are determined to be screen failures. All 
payments will be made when all of the data (case report forms) up to the point of going off study are 
submitted.  The site subcontracts do not specify how the per-patient reimbursement is to be 
allocated.  However, the following should be considered at each site as appropriate to successful 
implementation of the study: 
 
1. Staff time to implement recruitment and retention plan 
2. Recruiter transportation to community outreach events  
3. Participant compensation/remuneration 
4. Recruitment and retention tools 
H.  Determine and list site-specific recruitment and retention strategies based on evaluation of 
protocol, target population, clinic, and referral sources. 
 
1. Describe general strategies such as: 
a. Regularly contacting referral sources 
b. Advertisements and public relations 
c. Newspaper 
d. TV and radio 
e. Internet, social networking sites such as Pinterest, Twitter, and Facebook 
f. Direct mailings 
g. Investigator interviews 
h. Patient education lectures 
i. 
Investigator or coordinator educational sessions to relevant community 
organizations 
j. 
FAQ documents  
k. Mass media and press releases 
l. 
Partner with other studies 
m. Identify Spokespersons 
n. Volunteers        

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2. Describe recruitment strategies for special populations, such as women and minorities, such 
as: 
a. Perform cultural assessment of local communities 
b. Consider centralized minority coordinator 
c. Consider matched ethnicity recruitment coordinator 
d. Have translator available  
e. Minority community liaison 
f. Meet with minority community leaders 
g. Go to community meetings 
h. Establish relationships with churches 
i. 
Special needs participants 
j. 
Large print documents 
k. Arrange transportation 
Participating Organizations:  Revise Section II (below) to describe your actual recruitment strategies.  
Describe specifically how you will identify potential participants, screen potential participants, and 
begin the informed consent process. 
 
II. Active recruitment phase (Implementing the Recruitment Plan) 
 
1. Implement strategies as determined during pre-initiation phase of plan 
2. Consider non-compliance and retention potential  
a. Exclude participants unlikely to comply and stay on study – unless you can provide 
compensatory support and follow-up 
b. Known history of non-compliance 
c. Socially unstable 
d. Expressed difficulty with, and numerous objections to, protocol requirements 
e. Cavalier attitude toward protocol 
f. Verbalized a minimization of cancer risk 
g. Verbalized desire for “active immunization only” 
h. Consider multiple objections as red flag indicating possible retention/compliance 
problems 
3. Contact potentially eligible participants and pre-screen for initial eligibility.   
4. Assess eligibility of individual potential participants 
5. Build supportive relationship with participant 
6. Involve each participant’s social network/support system in decision-making 
7. Clarify any misconceptions 
8. Offer to help resolve manageable participants’ logistical problems  
9. Continuously evaluate the site recruitment plan  
a. Maintain screening log and reasons for ineligibility or non-enrollment.  Data concerning 
screening, recruitment, and resulting accrual will be forwarded from the Participating 

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Organizations to the CLO on a monthly basis.  Timeliness and compliance with this 
requirement will be monitored by the CLO. 
b. Each site should consider modifying recruitment plan if recruitment is lagging.  If 
necessary, ask the CLO for advice and assistance. 
 
Participating Organizations:  Revise Section III below to describe the activities you will employ to 
maintain contact with the study participants while on study and insure compliance with events, 
procedures, and study medication.  Please also describe any activities that you do to maintain a good 
relationship with them so that they might, if eligible, be willing to participate in future clinical trials.  The 
activities listed are ideas and suggestions. 
 
III. Retention and adherence phase – Be proactive 
 
1. Maintain communication with referring physicians re: participant progress 
2. Establish and maintain rapport among staff during follow-up 
a. Newsletters or other communication tools 
b. Adequate staff compensation 
c. Staff recognition/awards 
3. Establish and maintain rapport and communication with participants  
a. Identify and track red flags for possible attrition (but do not offer support that cannot be 
maintained):  
i. adverse effects/events (review protocol carefully, be prepared to respond to AE 
reports, inform participants as to what can be expected)  
ii. missed appointments 
iii. frequent appointment time changes 
iv. major personal or family events 
v. health deterioration 
vi. loss of support system 
b. Do not promise support that cannot be maintained 
c. Maintain current contact info for each participant 
d. Enlist support of participant’s social network 
i. Transportation 
ii. Encouragement 
iii. Protocol compliance 
e. Provide remuneration/compensation for expenses incurred as budget and local IRB 
regulations permit: 
i. Parking, meals, time lost from work, transportation, child care 
f. Ensure pleasant clinic visits 
i. Limit waiting room time and provide refreshments, if possible 
ii. Coordinate assessments (e.g., blood work, etc.) with visits 
iii. Flexible scheduling 

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iv. Toll-free numbers 
v. Ensure consistent staff contact person and access to PI 
vi. Establish and communicate schedule for contact with participant 
vii. Consider retention tools, such as calendars, newsletters, appointment cards, 
reminder cards and phone calls, certificates of appreciation, holiday cards 
g. Track participant withdrawals and reasons for withdrawal and communicate this 
information to the CLO 
Participating Organizations:  Section IV describes the activities of the CLO.  It should be left in your site’s 
plan for informational purposes.  Additionally, you are encouraged to describe any analysis or evaluation 
of recruitment that will occur at your site. 
 
 IV. Evaluation Phase 
1. During the study 
a. The CLO Recruitment Coordinator will continuously review study recruitment and 
adherence 
data from all tracking documents.  These will be summarized and forwarded on a 
monthly basis. 
b. The CPN Operations Committee will review the monthly reports and discuss possible 
revisions, protocol modifications, site closures, and other activities as needed. 
c. All discussions, recommendations, conclusions, and/or lessons learned will be 
documented with the possibility of publication in mind. 
d. Successful strategies will be shared with other participating organizations during 
teleconferences and via the Study Coordinator Memo. 
2. After the study 
a. Historically it has been difficult to reach recruitment goals across all cancer prevention 
studies.  In order to explore the obstacles sites are facing, the CLO will distribute a short 
survey to all participating sites at the study completion. The survey will target: site 
issues, inclusion/exclusion issues, time issues, CPN support, education and training.   
 
 
 
 
 
 
 
 

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APPENDIX C 
 
Was It Worth It Questionnaire 
 
Visit type (Time point):* 
 Week 55 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 
 
Pre-Vaccine Survey 
 
Visit type (Time point):* 
 Week 0 
Participant ID:  ______________________ 
Visit Date: __________________________ 
 
The purpose of these questions is to help us to understand more about how individuals who are at 
risk for developing colorectal cancer make the decision to participate in a vaccine study.   
 
Circle the answer or number that best describes your answer 
 
1. What do you think is your chance of developing colorectal cancer?  
   (Circle 0 for no chance and 10 for great chance) 
 
No chance 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Great 
chance 
 
2. Which of the following people did you talk to about the vaccine study? (Circle all that apply)  
 
        Spouse or significant other       Family Physician        Parent         Friend           Clergy 
 
 
      Other, please specify: ____________________________________________________________ 
 
3. What was the response of the person/s you talked to about the study? (Circle all that apply)  
   
a. Spouse or significant other 
Supportive 
Neutral 
Non-Supportive 
b. Family Physician 
Supportive 
Neutral 
Non-Supportive 
c. Parent 
Supportive 
Neutral 
Non-Supportive 
d. Friend 
Supportive 
Neutral 
Non-Supportive 
e. Clergy 
Supportive 
Neutral 
Non-Supportive 
f. Other, specify: 
_________________________ 
Supportive 
Neutral 
Non-Supportive 
 
4. How often, prior to receiving the vaccine, did you think that you should have a colonoscopy? 
 
Yearly             2 years             3 years            4 years           5 years               10 years 
 
Other, please specify (Please write your answer): 

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5. How important to your decision was it that you might get the following benefits from the vaccine: 
          
 
Not at 
all 
 
 
 
 
Very 
a. Decrease the number of polyps you develop 
0 
1 
2 
3 
4 
5 
b. Prevent you from developing polyps 
0 
1 
2 
3 
4 
5 
c. Prevent you from developing colorectal cancer 
0 
1 
2 
3 
4 
5 
d. Decrease the frequency that you have 
colonoscopies 
0 
1 
2 
3 
4 
5 
 
 
 

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Pre-Vaccine Decision Regret Scale 
 
 
 
 
 
 
 
 
Visit type (Time point):* 
 Week 0 
Participant ID:  ______________________ 
Visit Date: __________________________ 
 
Please reflect on the first decision you made about participating in the MUC1 vaccine trial for 
individuals with advanced colorectal adenoma after talking with your study doctor or a member of 
the research team. Please show how strongly you agree or disagree with these statements by circling 
a number from 1 (strongly agree) to 5 (strongly disagree) which best fits your views about your 
decision.  
 
Strongly 
Agree 
Agree 
Neither 
Agree Nor 
Disagree 
Disagree 
Strongly 
Disagree 
1. It was the right decision 
1 
2 
3 
4 
5 
2. I regret the choice that was 
made 
1 
2 
3 
4 
5 
3. I would go for the same 
choice if I had to do it over 
again 
1 
2 
3 
4 
5 
4. The choice did me a lot of 
harm 
1 
2 
3 
4 
5 
5. The decision was a wise one 
1 
2 
3 
4 
5 
 
Decision Regret Scale (copyright) AM O’Connor, 1996 University of Ottawa  
 
Perceived Stress 
 
The questions in this scale ask you about your feelings and thoughts during the last month. In each 
case, please circle the number that best represents how often you felt or thought a certain way by 
circling a number from 1 to 5. 
 
Never 
Almost 
Never 
Sometimes 
Fairly 
Often 
Very Often 
1. How often have you felt that 
you were able to control the 
important things in your life 
1 
2 
3 
4 
5 
2. How often have you felt 
confident about your ability to 
handle your personal problems? 
1 
2 
3 
4 
5 
3. How often have you felt that 
things were going your way? 
1 
2 
3 
4 
5 
4. How often have you felt 
difficulties were piling up so 
high that you could not 
overcome them? 
1 
2 
3 
4 
5 

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Pre-Vaccine Symptom Inventory 
 
Visit type (Time point):* 
 Week 0 
Participant ID:  ______________________ 
Visit Date: __________________________ 
 
Below is a list of problems and complaints that people sometimes have.  Read each item carefully, and 
select one of the numbered answers that best describes how much discomfort that problem has 
caused you in the past month, including today.  Please circle the number to the right of the problem.  
Answer each question by circling the answer as indicated.  If you change your mind, erase your first 
circle completely. 
 
 
Not at all 
A little bit 
Moderately 
Quite a bit 
Extremely 
1.  Nervousness or shakiness inside  
0 
1 
2 
3 
4 
2.  Faintness or dizziness 
 
0 
1 
2 
3 
4 
3.  Pains in heart or chest 
 
 
0 
1 
2 
3 
4 
4.  Suddenly scared for no reason 
 
0 
1 
2 
3 
4 
5.  Feeling lonely 
 
 
 
0 
1 
2 
3 
4 
6.  Feeling blue  
 
 
0 
1 
2 
3 
4 
7.  Feeling no interest in things  
0 
1 
2 
3 
4 
8.  Feeling fearful 
 
 
 
0 
1 
2 
3 
4 
9.  Nausea or upset stomach 
 
 
0 
1 
2 
3 
4 
10.  Trouble getting (catching) your breath 
0 
1 
2 
3 
4 
11.  Numbness or tingling in parts of your 
body 
 
0 
1 
2 
3 
4 
12.  Feeling hopeless about the future 
0 
1 
2 
3 
4 
13.  Feeling weak in parts of your body 
0 
1 
2 
3 
4 
14.  Feeling tense or keyed up  
0 
1 
2 
3 
4 
15.  Spells of terror or panic 
 
  
0 
1 
2 
3 
4 
16.  Feeling so restless that you couldn't sit 
still 
0 
1 
2 
3 
4 
17.  Feelings of worthlessness  
0 
1 
2 
3 
4 
 
 
 
 

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Pre-Vaccine Health 
 
Visit type (Time point):* 
 Week 0 
Participant ID:  ______________________ 
Visit Date: __________________________ 
 
The survey below asks for your views about your health. This information will help better understand how you 
feel and how well you are able to do your usual activities. Answer each question by selecting the answer as 
indicated. If you are unsure about how to answer a question, please give the best answer you can. 
 
1. In general, would you say that your health is:     
 Excellent      
 Very good      
 Good      
 Fair      
 Poor 
 
 
2. The following questions are about activities you might do during a typical day. Does your health now limit you in 
these activities? If so, how much? 
a. Moderate activities, such as moving a table, pushing a vacuum cleaner, bowling, or playing golf?  
      
 Yes, limited a lot               
 Yes, limited a little               
 No, not limited at all 
b. Climbing several flights of stairs? 
 Yes, limited a lot               
 Yes, limited a little               
 No, not limited at all 
 
 
3. During the past 4 weeks, have you had any of the following problems with your work or other regular daily activities 
as a result of your physical health? 
     a. Accomplished less than you would like?   
 Yes   
 No      
     b. Were limited in the kind of work or other activities?   
 Yes   
 No      
 
 
4. During the past 4 weeks, have you had any of the following problems with your work or other regular daily activities 
as a result of any emotional problems (such as feeling depressed or anxious)? 
     a. Accomplished less than you would like?   
 Yes   
 No      
     b. Didn’t do work or other activities as carefully as usual?   
 Yes   
 No      
 
 
5. During the past 4 weeks, how much did pain interfere with your normal work (including both work outside the 
home and around the house)? 
        
 Not at all    
 A little bit    
 Moderately    
 Quite a bit    
 Extremely 
 
 
 
 
 

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6. These questions are about how you feel and how things have been with you during the past 4 weeks. For each 
question, please give the one answer that comes closest to the way you have been feeling. How much of the time 
during the past 4 weeks… 
 
a. Have you felt calm and peaceful?   
All of the time  
Most of the time  
A good bit of the time  
Some of the time 
A little of the time  
None 
of the time 
b. Did you have a lot of energy?  
All of the time  
Most of the time  
A good bit of the time  
Some of the time 
A little of the time  
None 
of the time 
c. Have you felt downhearted and blue?  
All of the time  
Most of the time  
A good bit of the time  
Some of the time 
A little of the time  
None 
of the time 
 
 
7. During the past 4 weeks, how much of the time has your physical health or emotional problems interfered with your 
social activities (like visiting friends, relatives, etc.)? 
     
 All of the time     
 Most of the time     
 Some of the time     
 A little of the time     
 None of the time 
 
 

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Post-Vaccine Survey 
 
Visit type (Time point):* 
 Week 53    
 Week 156 or early termination 
Participant ID:  ______________________ 
Visit Date: __________________________ 
 
The purpose of these questions is to help us to understand more about how individuals who are at 
risk for developing colorectal cancer make the decision to participate in a vaccine study.  Please circle 
the response that best describes your answer. 
 
1. What do you think your chance of developing colorectal cancer is since you have been vaccinated?  
(Circle 0 for no chance and 10 for great chance) 
 
No chance 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Great 
chance 
 
 
 
2. What do you think your chance of developing colorectal cancer would have been if you had not 
received the vaccine? 
 
No chance 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Great 
chance 
 
 
 
3. To what extent do you think that the vaccine will provide you with protection (immunity) against the 
development polyps?  
 
No chance 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Great 
chance 
   
 
 
4. If you feel the vaccine will provide protection (immunity) against the development of polyps, how 
long do you think the protection will last?   
 
No immunity               Weeks                Months               Years              Lifetime  
 
 
 
 
 
 
 

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5. Do you think that the vaccine will provide you with protection (immunity) against developing 
colorectal cancer?   
 
No chance 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Great 
chance 
 
a. If so, how long do you think the vaccine will provide protection (immunity) against the 
development of colorectal cancer? 
 
Lifetime                  Weeks                    Months                  Years  
 
b. How often do you think that you should have a colonoscopy now that you have received the 
vaccine? 
Yearly 
2 years 
3 years 
4 years 
5 years 
10 years 
Other 
If other, please specify: _________________________________________________ 
 
6. Would you have been vaccinated if the following individuals were not supportive? 
 
a. Spouse or significant other 
Yes 
No 
b. Family Physician 
Yes 
No 
c. Parent 
Yes 
No 
d. Friend 
Yes 
No 
e. Clergy 
Yes 
No 
f. Other, specify: _________________________ 
Yes 
No 
 
7. Would you get vaccinated if you had to pay for the vaccine?  
 Yes     
 Maybe     
 No      
 
8. How far would you travel to receive the vaccine? 
 
Less than 10 miles         Over 10 miles           
Up to 100 miles        
Anywhere 
 
9. Would you get vaccinated if you were told that the potential side effects for the vaccine were 
unknown? 
 Yes     
 Maybe     
 No      
 
10. Would you get vaccinated if you were told that the safety of the vaccine was unknown? 
 
 Yes     
 Maybe     
 No      
 

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Post-Vaccine Decision Regret Scale 
 
Visit type (Time point):* 
 Week 53    
 Week 156 or early termination 
Participant ID:  ______________________ 
Visit Date: __________________________ 
 
Please reflect on the first decision you made about participating in the MUC1 vaccine trial for 
individuals with advanced colorectal adenoma after talking with your study doctor or a member of 
the research team. Please show how strongly you agree or disagree with these statements by circling 
a number from 1 (strongly agree) to 5 (strongly disagree) which best fits your views about your 
decision.  
 
Strongly 
Agree 
Agree 
Neither 
Agree Nor 
Disagree 
Disagree 
Strongly 
Disagree 
1. It was the right decision 
1 
2 
3 
4 
5 
2. I regret the choice that was 
made 
1 
2 
3 
4 
5 
3. I would go for the same 
choice if I had to do it over 
again 
1 
2 
3 
4 
5 
4. The choice did me a lot of 
harm 
1 
2 
3 
4 
5 
5. The decision was a wise one 
1 
2 
3 
4 
5 
 
Decision Regret Scale (copyright) AM O’Connor, 1996 University of Ottawa  
 
Post-Vaccine Perceived Stress 
 
The questions in this scale ask you about your feelings and thoughts during the last month. In each 
case, please circle the number that represents how often you felt or thought a certain way. 
 
Never 
Almost 
Never 
Sometimes 
Fairly 
Often 
Very Often 
1. How often have you felt that 
you were able to control the 
important things in your life 
1 
2 
3 
4 
5 
2. How often have you felt 
confident about your ability to 
handle your personal problems? 
1 
2 
3 
4 
5 
3. How often have you felt that 
things were going your way? 
1 
2 
3 
4 
5 
4. How often have you felt 
difficulties were piling up so 
high that you could not 
overcome them? 
1 
2 
3 
4 
5 

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Post-Vaccine Symptom Inventory 
 
Visit type (Time point):* 
 Week 53    
 Week 156 or early termination 
Participant ID:  ______________________ 
Visit Date: __________________________ 
 
Below is a list of problems and complaints that people sometimes have.  Read each item carefully, and 
select one of the numbered descriptors that best describes how much discomfort that problem has 
caused you in the past month, including today.  Please circle the number to the right of the problem.  
Please do not skip any items.  If you change your mind, erase your first circle completely. 
 
 
Not at all 
A little bit 
Moderately 
Quite a bit 
Extremely 
1.  Nervousness or shakiness inside  
0 
1 
2 
3 
4 
2.  Faintness or dizziness 
 
0 
1 
2 
3 
4 
3.  Pains in heart or chest 
 
 
0 
1 
2 
3 
4 
4.  Suddenly scared for no reason 
 
0 
1 
2 
3 
4 
5.  Feeling lonely 
 
 
 
0 
1 
2 
3 
4 
6.  Feeling blue  
 
 
0 
1 
2 
3 
4 
7.  Feeling no interest in things  
0 
1 
2 
3 
4 
8.  Feeling fearful 
 
 
 
0 
1 
2 
3 
4 
9.  Nausea or upset stomach 
 
 
0 
1 
2 
3 
4 
10.  Trouble getting (catching) your breath 
0 
1 
2 
3 
4 
11.  Numbness or tingling in parts of your 
body 
 
0 
1 
2 
3 
4 
12.  Feeling hopeless about the future 
0 
1 
2 
3 
4 
13.  Feeling weak in parts of your body 
0 
1 
2 
3 
4 
14.  Feeling tense or keyed up  
0 
1 
2 
3 
4 
15.  Spells of terror or panic 
 
  
0 
1 
2 
3 
4 
16.  Feeling so restless that you couldn't sit 
still 
0 
1 
2 
3 
4 
17.  Feelings of worthlessness  
0 
1 
2 
3 
4 
 
Thank you! 
 
 
 
 

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Post-Vaccine Health 
 
Visit type (Time point):* 
 Week 53    
 Week 156 or early termination 
Participant ID:  ______________________ 
Visit Date: __________________________ 
 
The survey below asks for your views about your health. This information will help better understand how you 
feel and how well you are able to do your usual activities. Answer every question by selecting the answer as 
indicated. If you are unsure about how to answer a question, please give the best answer you can. 
 
1. In general, would you say that your health is:     
 Excellent      
 Very good      
 Good      
 Fair      
 Poor 
 
2. The following questions are about activities you might do during a typical day. Does your health now limit you in 
these activities? If so, how much? 
a. Moderate activities, such as moving a table, pushing a vacuum cleaner, bowling, or playing golf?  
      
 Yes, limited a lot               
 Yes, limited a little               
 No, not limited at all 
b. Climbing several flights of stairs? 
 Yes, limited a lot               
 Yes, limited a little               
 No, not limited at all 
 
 
3. During the past 4 weeks, have you had any of the following problems with your work or other regular daily activities 
as a result of your physical health? 
     a. Accomplished less than you would like?   
 Yes   
 No      
     b. Were limited in the kind of work or other activities?   
 Yes   
 No      
 
 
4. During the past 4 weeks, have you had any of the following problems with your work or other regular daily activities 
as a result of any emotional problems (such as feeling depressed or anxious)? 
     a. Accomplished less than you would like?   
 Yes   
 No      
     b. Didn’t do work or other activities as carefully as usual?   
 Yes   
 No      
 
 
5. During the past 4 weeks, how much did pain interfere with your normal work (including both work outside the 
home and around the house)? 
        
 Not at all    
 A little bit    
 Moderately    
 Quite a bit    
 Extremely 
 
 
 
 
 
 
 

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6. These questions are about how you feel and how things have been with you during the past 4 weeks. For each 
question, please give the one answer that comes closest to the way you have been feeling. How much of the time 
during the past 4 weeks… 
a. Have you felt calm and peaceful?   
All of the time  
Most of the time  
A good bit of the time  
Some of the time 
A little of the time  
None 
of the time 
 
b. Did you have a lot of energy?  
All of the time  
Most of the time  
A good bit of the time  
Some of the time 
A little of the time  
None 
of the time 
 
c. Have you felt downhearted and blue?  
All of the time  
Most of the time  
A good bit of the time  
Some of the time 
A little of the time  
None 
of the time 
 
7. During the past 4 weeks, how much of the time has your physical health or emotional problems interfered with your 
social activities (like visiting friends, relatives, etc.)? 
     
 All of the time     
 Most of the time     
 Some of the time     
 A little of the time     
 None of the time 
Thank you! 
 
 
 
 
 
 
 

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APPENDIX E 
 
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 an envelope, fax number, or email address for you. 
 
What to record: 
The pilot studies 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.  
 
 
 
 
 
 
 
 
 
 

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About Injection Site Reactions  
 
Measuring the size of the redness 
(erythema): 
This picture shows redness of the skin. To 
measure this, use a tape measure or ruler to 
measure the maximum distance from one 
side of the red patch to the other in 
centimeters. It might be helpful to measure 
it across the red patch both from side to side 
and from top to bottom. Record the longest 
distance. 
 
Pain and Tenderness: 
You may experience pain at the injection 
site.  There are two possible types.  One is 
general muscle pain or achiness at the site 
that is present even when you’re not 
touching the area, such as with movement 
or even sitting.  The other type is tenderness, which is pain when you touch the injection site.  
Please record these separately. 
 
Swelling or Induration: 
Swelling or induration is firmness, like the bump that may be experienced after a mosquito bite.  
The easiest way to measure it is to use your fingertip to feel the edge of the firmness, and then 
make a mark with an ink pen at one edge. Make another mark at the opposite edge.  It might 
be helpful to measure and mark the swelling or induration both from side to side and from top 
to bottom.  To measure this, use a tape measure or ruler to measure the maximum distance 
between the two marks in centimeters. Record the longest distance. 
 
Warmth and itching: 
Document when warmth or itching begins and when these symptoms go away. 
 
 
________________________________                                 ______________________________                              
Your Signature 
 
 
 
 
 
 
 
Date 
 
________________________________                                 ______________________________                              
Study Coordinator Signature  
 
 
 
 
             Date 
 
 
 
 

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MAY2013-01-01,“ Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Vaccine in Patients with Newly Diagnosed 
Advanced Adenomas” 
 
Vaccine Report Card 
 
Participant ID __________________________ Date of Injection ________________________ 
 
Instructions:  Please complete this “report card” at 2 days, 7 days, and 14 days after your injection.  Bring it to your next study visit or return it to 
the study team by mail, fax, or email. 
 
 
Possible 
side effects 
Date Symptom 
Appeared 
2 days after injection 
Date ______________ 
7 days after injection 
Date ______________ 
14 days after injection 
Date ______________ 
Date Symptom 
Disappeared 
Redness at 
the injection 
site 
 
□ None 
□ Yes.  It measured 
 
 
__________ centimeters 
□ None 
□ Yes.  It measured 
 
 
_________ centimeters 
□ None 
□ Yes.  It measured 
 
 
_________ centimeters 
 
Pain at the 
injection site  
without 
touching 
 
□ None 
□ A little, but it didn’t interfere 
with normal activity 
□ Some, required OTC* 
medications  for more than 
24 hours or limited normal 
activity 
□ A lot, required prescription 
medications, interfered with 
normal activity 
□ Required ER visit or 
hospitalization 
 
□ None 
□ A little, but it didn’t interfere 
with normal activity 
□ Some, required OTC* 
medications for more than 24 
hours or limited normal 
activity 
□ A lot, required prescription 
medications, interfered with 
normal activity 
□ Required ER visit or 
hospitalization 
□ None 
□ A little, but it didn’t interfere 
with normal activity 
□ Some, required OTC* 
medications for more than 24 
hours or limited normal 
activity 
□ A lot, required prescription 
medications, interfered with 
normal activity 
□ Required ER visit or 
hospitalization 
 

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Possible 
side effects 
Date Symptom 
Appeared 
2 days after injection 
Date ______________ 
7 days after injection 
Date ______________ 
14 days after injection 
Date ______________ 
Date Symptom 
Disappeared 
Tenderness 
(Pain at the 
injection site 
with touch) 
 
□ None 
□ A little, but it didn’t interfere 
with normal activity 
□ Some, required OTC* 
medications  for more than 
24 hours or limited normal 
activity 
□ A lot, required prescription 
medications, interfered with 
normal activity 
□ Required ER visit or 
hospitalization 
□ None 
□ A little, but it didn’t interfere 
with normal activity 
□ Some, required OTC* 
medications  for more than 
24 hours or limited normal 
activity 
□ A lot, required prescription 
medications, interfered with 
normal activity 
□ Required ER visit or 
hospitalization 
□ None 
□ A little, but it didn’t interfere 
with normal activity 
□ Some, required OTC* 
medications  for more than 
24 hours or limited normal 
activity 
□ A lot, required prescription 
medications, interfered with 
normal activity 
□ Required ER visit or 
hospitalization 
 
Swelling/ 
Induration** 
 
□ None 
□ Yes.  It measured 
 
__________ centimeters 
□ None 
□ Yes.  It measured 
 
__________ centimeters 
□ None 
□ Yes.  It measured 
 
__________ centimeters 
 
Itching at site 
 
□ None 
□ Yes 
□ None 
□ Yes 
□ None 
□ Yes 
 
Skin warmth 
at site 
 
□ None 
□ Yes 
□ None 
□ Yes 
□ None 
□ Yes 
 
* OTC – Over the counter medications such as Tylenol® or ibuprofen. 
** Firm, raised swelling.   
 
 
 
 
 
 
 
 

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If you experience any other symptoms that you would like to report, please make note of them on this page.  Be sure to write down the date the 
symptom appeared and the date the symptom disappeared.  If you took any medications for the symptom or visited a doctor or hospital for the 
symptom, please inform the study team. 
 

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APPENDIX  F 
 
NAFLD Activity Score 
 
 
The Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) is a validated score that is used to 
grade disease activity in patients with NAFLD.   The NAS is the sum of the biopsy's individual scores for 
steatosis (0 to 3), lobular inflammation (0 to 2), hepatocellular ballooning (0 to 2), and fibrosis (0 to 4). 
An NAS of 1 or 2 corresponds to NAFL, 3 to 4 corresponds to borderline NASH, and a score ≥5 
corresponds to NASH. (See "Histologic scoring systems for chronic liver disease", section on 
'Nonalcoholic fatty liver disease'.) 
 
Please note that for this protocol, the calculation of the NAS applies only for the determination of 
eligibility for individuals with a diagnosis of Non-Alcoholic Steatohepatitis (NASH).