The following datasets contain the data available for EPPT MAY2013-01-01. The description and documentation for each file is listed below. SAS7bdat and CSV versions of the actual data will be available to CDAS projects approved to use this study's data.

Analysis Datasets

Raw Datasets

These 49 datasets contain the raw form data received, excluding PII.

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Trial Summary

This randomized phase II clinical trial studied how well the MUC1 peptide-poly-ICLC adjuvant vaccine works in treating patients with recently diagnosed advanced colon polyps (adenomatous polyps). These polyps may potentially develop into colorectal cancer given time. This vaccine may help the body build an effective immune response to kill the polyp cells. 110 volunteers were randomized and 94 completed the study.

The MUC1 peptide-poly-ICLC adjuvant vaccine was administered in weeks 0, 2, and 10 with a booster injection in week 53.

Patients are randomized to 1 of 2 treatment arms:

• Arms
  • ARM I: MUC1 peptide-poly-ICLC adjuvant vaccine injection was administered in weeks 0, 2, and 10 with a booster injection in week 53.
  • ARM II: Saline injection was administered in weeks 0, 2, and 10 with a booster injection in week 53.

Enrollment Statistics

Target Enrollment: 120

Actual Enrollment: 130

Actual Registration: 130

• 110 people randomized
  • 54 in Arm I (54 out of 110 randomized): MUC1 Vaccine
    • 48 completed the study.
    • 2 withdrew from study.
    • 3 lost to follow-up.
    • 1 dropped due to other reasons.
  • 56 in Arm II (56 out of 110 randomized): Placebo
    • 46 completed the study
    • 5 withdrew from study.
    • 1 dropped due to adverse event.
    • 2 lost to follow-up.
    • 2 dropped due to other reasons.
• 20 people were not randomized (20 of 130 registered)

Statistical Analysis and Total Study Population Demographics:

• Age (years):
  • Mean: 59.3
  • Range: 40-70
  • Median: 59
• Height (cm):
  • Mean: 172
  • IQR: 165-180
  • Range: 149-191
  • Median: 173
• Weight (kg):
  • Mean: 90
  • IQR: 77-101
  • Range: 53-150
  • Median: 173
• Gender:
  • Male: 71 (64.6%)
  • Female: 39 (35.4%)

Eligibility Criteria

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
• 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

The Schema is a timeline of the study. It indicates start/end points, visits expected, major testing to be done, and any other information that is crucial to understanding how the study was completed.

Over the course of this study 1,743 biospecimens were collected. Research blood kits were provided by BAP Kit Building (Biospecimen Accessioning and Processing Core Facility) and were used for collecting and shipping all research samples for analysis. Blood samples were taken at baseline, week 2, week 10, week 12, week 52, week 55, and week 156. Tissue specimens were taken only at baseline and week 156.

Blood samples were collected between Mondays and Thursdays so that they could be shipped overnight for next day analysis. For analysis, the heparinized blood will centrifuged over a density gradient (Ficoll) to separate the plasma and PBMC. The plasma was then collected, aliquoted, and stored at -20°C. The PBMC will be washed several times, aliquoted, slowly frozen to -70 to -80°C in human serum with 20% DMSO and stored in the vapor phase of liquid nitrogen.

Tissue specimens were collected as paraffin blocks and/or unstained slides from the polyps/adenomas removed during the routing colonoscopy both pre- and post-intervention. Institutions that were unable to submit paraffin blocks could send five 5-micron unstained slide from each advanced adenomas.

*No Specimen Available

Results/Findings:

Transient, mild-to-moderate injection site reactions unrelated to IL12 DNA dose were common. Increases in HCV-specific IFNγ production occurred in 15/20 (75%) participants. Increases in the frequency of HCV-specific CD4+ and CD8+ T cells occurred at all dose levels, with the greatest increases seen at 1.0 mg of INO-9012. HCV-specific CD8+ and CD4+ T-cell activities increased in 16/18 (89%) and 14/17 (82%) participants with available data, respectively. The vaccine regimen was safe and induced HCV-specific CD4+ and CD8+ cellular immune responses of modest magnitude in most HCV-infected participants. The addition of 1.0 mg of IL12 DNA provided the best enhancement of immune responses. The vaccine regimen had little effect on controlling HCV viremia.