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Vaccine Therapy in Treating Patients With Newly Diagnosed Advanced Colon Polyps

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02134925
First received: May 7, 2014
Last updated: March 13, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention Phase
Colorectal Adenoma
Colorectal Adenoma With Severe Dysplasia
Colorectal Tubulovillous Adenoma
Other: Laboratory Biomarker Analysis
Biological: MUC1 Peptide-Poly-ICLC Vaccine
Other: Quality-of-Life Assessment
Other: Saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Prevention
Official Title: Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Vaccine in Patients With Newly Diagnosed Advanced Adenomas

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Change in anti-MUC1 immunoglobulin G (IgG) levels as determined by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: Week 0 to week 12 ]
    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.


Secondary Outcome Measures:
  • Adenoma recurrence rate assessed using surveillance exams [ Time Frame: Up to 3 years ]
  • Booster response [ Time Frame: At week 55 ]
    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.

  • Incidence of adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 57 weeks ]
    The maximum grade for each type of adverse event will be recorded for each participant and frequency tables will be reviewed to determine the overall patterns. The number and severity of adverse events (overall and by arm) will be tabulated and summarized across all grades. Grade 3+ adverse events will be similarly described and summarized separately. Frequency distributions, graphical techniques, and other descriptive measures will form the basis of these analyses.

  • Incidence of participant-reported injection site reaction collected using the participant completed Vaccine Report Card [ Time Frame: Up to 57 weeks ]
    Descriptive statistics will be used to summarize these data and compare the data between study arms.

  • Proportion of patients with at least a 2‐fold increase in the IgG ratio [ Time Frame: At 12 weeks ]

Other Outcome Measures:
  • Anti‐MUC1 antibody titer by ELISA [ Time Frame: At approximately week 156 ]
    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.

  • Change in levels of circulating MDSC in peripheral blood mononuclear cells by flow cytometry [ Time Frame: Baseline to up to 3 years ]
    MDSC levels will be correlated with anti‐MUC1 antibody levels and adenoma recurrence. Descriptive statistics and simple scatter plots will be generated to review the continuous biomarker data. In addition, for continuous biomarker values, the actual and percent 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.

  • Change in MUC1 expression [ Time Frame: Baseline to up to 3 years ]
    Descriptive statistics and simple scatter plots will be generated to review the continuous biomarker data. In addition, for continuous biomarker values, the actual and percent 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.

  • Establishment of a biospecimen repository archive including live cells, plasma, and germline DNA for future immunologic and other assays [ Time Frame: Up to 3 years ]

Enrollment: 120
Study Start Date: June 2014
Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (MUC1 peptide-poly-ILCLC adjuvant vaccine)
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
Correlative studies
Biological: MUC1 Peptide-Poly-ICLC Vaccine
Given SC
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Placebo Comparator: Arm II (saline)
Participants receive saline SC in weeks 0, 2, and 10 and a booster injection in week 53.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Saline
Given SC
Other Name: Sodium Chloride 0.9%

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02134925

Locations
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Kansas City Veterans Affairs Medical Center
Kansas City, Missouri, United States, 64128
United States, Pennsylvania
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States, 15232
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Robert Schoen Mayo Clinic
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02134925     History of Changes
Obsolete Identifiers: NCT02886000
Other Study ID Numbers: NCI-2014-01080
NCI-2014-01080 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
HHSN261201200042I
N01-CN-2012-00042
MAY2013-01-01 ( Other Identifier: Mayo Clinic )
MAY2013-01-01 ( Other Identifier: DCP )
N01CN00042 ( US NIH Grant/Contract Award Number )
P30CA015083 ( US NIH Grant/Contract Award Number )
Study First Received: May 7, 2014
Last Updated: March 13, 2017

Additional relevant MeSH terms:
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Vaccines
Poly ICLC
Immunologic Factors
Physiological Effects of Drugs
Interferon Inducers

ClinicalTrials.gov processed this record on March 24, 2017