Vaccine Therapy in Treating Patients With Newly Diagnosed Advanced Colon Polyps

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.

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