Vaccine Therapy in Treating Patients With Newly Diagnosed Advanced Colon Polyps
|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 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|
- 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.
- 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 ]
- 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 ]
|Study Start Date:||June 2014|
|Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
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 studiesBiological: MUC1 Peptide-Poly-ICLC Vaccine
Given SCOther: Quality-of-Life Assessment
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 studiesOther: Quality-of-Life Assessment
Other Name: Quality of Life AssessmentOther: Saline
Other Name: Sodium Chloride 0.9%
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02134925
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02114|
|United States, Minnesota|
|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|
|University of Puerto Rico|
|San Juan, Puerto Rico, 00936|
|Principal Investigator:||Robert Schoen||Mayo Clinic|