Vaccine Therapy in Treating Patients With Newly Diagnosed Advanced Colon Polyps

Colorectal Adenoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02886000
• Other study ID #: NCI-2014-01080
• Secondary ID: NCI-2014-01080HH
• Status: Recruiting
• Phase: Phase 2
• First received: August 23, 2016
• Last updated: September 6, 2016
• Start date: June 2014

Study information

• Verified date: August 2016
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Adenoma
• Colorectal Adenoma
• Colorectal Adenoma With Severe Dysplasia
• Colorectal Tubulovillous Adenoma

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Biological:
• MUC1 Peptide-Poly-ICLC Vaccine
Given SC

Other:
• Quality-of-Life Assessment
Ancillary studies
• Saline
Given SC

Locations

Country	Name	City	State
Puerto Rico	University of Puerto Rico	San Juan
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Anti-MUC1 antibody titer by ELISA	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.	At approximately week 156	No
Other	Change in levels of circulating MDSC in peripheral blood mononuclear cells by flow cytometry	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.	Baseline to up to 3 years	No
Other	Change in MUC1 expression	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.	Baseline to up to 3 years	No
Other	Establishment of a biospecimen repository archive including live cells, plasma, and germline DNA for future immunologic and other assays		Up to 3 years	No
Primary	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	No
Secondary	Adenoma recurrence rate assessed using surveillance exams		Up to 3 years	No
Secondary	Booster response		At week 55	No
Secondary	Booster response		At week 52	No
Secondary	Incidence of adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0	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.	Up to 57 weeks	Yes
Secondary	Incidence of participant-reported injection site reaction collected using the participant completed Vaccine Report Card	Descriptive statistics will be used to summarize these data and compare the data between study arms.	Up to 57 weeks	No
Secondary	Proportion of patients with at least a 2-fold increase in the IgG ratio		At 12 weeks	No