Vaccine Therapy in Treating Patients With Newly Diagnosed Advanced Colon Polyps

Study Overview
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Brief Summary
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This randomized phase II clinical trial studies how well MUC1 peptide-poly-ICLC adjuvant vaccine works in treating patients with newly diagnosed advanced colon polyps (adenomatous polyps). Adenomatous polyps are growths in the colon that may develop into colorectal cancer over time. Vaccines made from peptides may help the body build an effective immune response to kill polyp cells. MUC1 peptide-poly-ICLC adjuvant vaccine may also prevent the recurrence of adenomatous polyps and may prevent the development of colorectal cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To compare the immunogenicity at week 12 of a MUC1 peptide vaccine with adjuvant (MUC1 peptide-poly-ICLC adjuvant vaccine) (administered at 0, 2, and 10 weeks) in participants with a history of an advanced adenoma, randomized to receive MUC1 peptide vaccine versus placebo. SECONDARY OBJECTIVES: I. To evaluate the ability of the vaccine to elicit a long-term memory response. II. 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. III. To compare the adenoma recurrence rates between MUC1 and placebo by excluding the following types of adenomas: participants with adenomas =< 5 mm; participants with adenomatous tissue which may represent residual adenoma at the site of the previous advanced adenoma; participants with adenomatous tissue detected in the same segment of the bowel as the previous advanced adenoma. IV. To assess adverse events to the MUC1 peptide vaccine in comparison to placebo during Parts I and II. V. To assess patient reported injection site reaction events from the Vaccine Report Card. TERTIARY OBJECTIVES: I. 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. II. To evaluate MUC1 expression on baseline advanced adenomas and on recurrent adenomas detected at surveillance colonoscopy. III. 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. IV. To establish a biospecimen repository archive including live cells, plasma, and germline deoxyribonucleic acid (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. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Participants receive MUC1 peptide-poly-ICLC adjuvant vaccine subcutaneously (SC) in weeks 0, 2 and 10 and a booster injection in week 53. ARM II: Participants receive saline SC in weeks 0, 2, and 10 and a booster injection in week 53. After completion of treatment, patients are followed up every 6 months for up to 3 years.

Official Title
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Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Vaccine in Patients With Newly Diagnosed Advanced Adenomas

Conditions
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Colorectal Adenoma, Colorectal Adenoma With Severe Dysplasia, Colorectal Tubulovillous Adenoma

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Biological: MUC1 Peptide-Poly-ICLC Vaccine
* Other: Quality-of-Life Assessment
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of at least one of the following conditions in the previous 12 months: Colorectal adenoma(s) >= 1 cm in maximal diameter Colorectal adenoma(s) with villous or tubulovillous histology Colorectal adenoma(s) with high grade (severe) dysplasia Presumptive evidence that all adenomatous lesions, including qualifying advanced adenoma, have been completely removed Ability to understand and the willingness to sign a written informed consent document Willingness to undergo screening tests and procedures Willingness to provide blood samples for toxicity monitoring and research purposes 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 Willingness to employ adequate contraception through week 53 of the study; note: 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 Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) Hemoglobin greater than 90% of the lower limit of institutional normal Platelets >= 100 B/L (10^9/L) White blood cell (WBC) > 2.5 B/L (10^9/L) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal Alkaline phosphatase =< 1.5 x institutional upper limit of normal Total bilirubin =< 1.5 x institutional upper limit of normal Blood urea nitrogen (BUN) =< 1.5 x institutional upper limit of normal Creatinine =< 1.5 x institutional upper limit of normal Antinuclear antibody (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 Exclusion Criteria: History of any colorectal cancer History of other malignancy =< 5 years prior to the registration/randomization evaluation, with the exception of basal cell or squamous cell skin cancer 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 Acquired immunosuppressive diseases such as active human immunodeficiency virus (HIV) infection or congenital diseases of immunity History of heritable cancer syndrome (familial adenomatous polyposis [FAP], hereditary nonpolyposis colorectal cancer [HNPCC]) History of auto-immune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, scleroderma, multiple sclerosis, Hashimoto's thyroiditis, or Grave's disease Current or planned use of immunomodulators including: infliximab, 6-MP (mercaptopurine), methotrexate, cyclosporine, or other immunomodulatory drugs History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agent Pregnant women Breastfeeding women 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 Division of Cancer Prevention (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) 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) Any use of oral corticosteroids =< 12 weeks prior to registration/randomization

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (MUC1 peptide-poly-ILCLC adjuvant vaccine)<br>Participants receive MUC1 peptide-poly-ICLC adjuvant vaccine SC in weeks 0, 2 and 10 and a booster injection in week 53. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Biological: MUC1 Peptide-Poly-ICLC Vaccine<br>* Given SC<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|
| Placebo Comparator: Arm II (saline)<br>Participants receive saline SC in weeks 0, 2, and 10 and a booster injection in week 53. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Saline<br>* Given SC<br>* Other names: Sodium Chloride 0.9%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Anti-MUC1 Immunoglobulin G (IgG) Levels as Determined by Enzyme-linked Immunosorbent Assay (ELISA) | The ratio of the week 12 to week 0 IgG levels will be calculated and compared between the MUC1 vaccine and placebo. The Wilcoxon Rank-Sum test will be used. For all measurements of response (i.e. the primary endpoint), the 95% confidence intervals will also be provided. | Week 0 to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adenoma Recurrence Rate | The secondary endpoint for Part 3 will evaluate the adenoma recurrence rate from surveillance exams. The rate is defined as the percentage of participants with adenoma recurrence. | At least one year and up to 3 years | 
| Booster Response | 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. The IgG ratios are summarized according to the following categories : <1, 1-<1.5, 1.5-<2, and >=2 (1-year response rate). | At week 55 | 
| Participant-reported Injection Site Reactions - Redness at the Injection Site, Swelling/Induration, Itching at Site, and Skin Warmth at Site | Participant-reported injection site reaction information is collected by the use of a participant-completed Vaccine Report Card. Participant-reported injection site reactions will be compared between study arms and are summarized below for redness at the injection site, swelling/induration, itching at site, and skin warmth at site. | Up to 55 weeks | 
| Participant-reported Injection Site Reactions - Pain at the Injection Site Without Touching, and Tenderness (Pain at the Injection Site With Touch) | Participant-reported injection site reaction information is collected by the use of a participant-completed Vaccine Report Card. Participant-reported injection site reactions will be compared between study arms and are summarized below for pain at the injection site without touching, and tenderness (pain at the injection site with touch). | Up to 55 weeks | 
| Number of Patients With at Least a 2-Fold Increase in the IgG Ratio | The frequency and percentage of patients with at least a 2-fold increase in the IgG Ratio will be calculated and compared between the MUC1 vaccine and placebo. The Fisher's exact test will be used. | At 12 weeks |