MUC1 Vaccine in Preventing Lung Cancer in Current and Former Smokers at High Risk for Lung Cancer

Study Overview
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Brief Summary
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This pilot phase I trial studies the side effects and how well MUC1 peptide-Poly-ICLC vaccine works in preventing lung cancer in current and former smokers at high risk for lung cancer. Vaccines made from peptides may help the body build an effective immune response to kill cells. MUC1 peptide-Poly-ICLC vaccine may stimulate the body's immune system and slow or stop the changes from normal to pre-cancer to cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Immunogenicity of the vaccine, assessed at week 12, based on the increase in IgG anti-MUC1 antibody titer over the pre-vaccination levels. II. Safety, assessed throughout the trial and continued observation for 24 weeks. SECONDARY OBJECTIVES: I. To explore potential differences, if any, in the immunogenicity of the vaccine (as assessed at week 12 by the IgG anti-MUC1 antibody titer ratio) in current versus (vs.) former smokers. II. To evaluate pre-vaccination levels of circulating myeloid derived suppressor cells (MDSC) and correlate with the ability to respond to the vaccine. EXPLORATORY OBJECTIVES: I. To explore immune response at week 24. II. To explore the relationship between chronic obstructive pulmonary disease (COPD) status at pre-registration and immune response in current versus former smokers. III. To explore the impact of the MUC1 peptide-Poly-ICLC vaccine (MUC1/Poly-ICLC vaccine) on inflammation-related high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels. IV. To explore the impact of baseline levels of hsCRP and IL-6 on the ability to successfully vaccinate with MUC1/Poly-ICLC. V. To establish a biospecimen repository archive: frozen peripheral blood live cells and plasma for future more detailed and comprehensive immunologic assays, including direct testing of anti-MUC1 T cell immunity. OUTLINE: Patients receive MUC1 peptide-Poly-ICLC vaccine subcutaneously (SC) at weeks 0, 2, and 10. After completion of study treatment, patients may be followed up at week 28.

Official Title
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A Pilot Study of MUC1 Vaccine in Current and Former Smokers at High Risk for Lung Cancer

Conditions
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Lung Carcinoma

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Biological: MUC1 Peptide-Poly-ICLC Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PRE-REGISTRATION INCLUSION CRITERIA Smoking history of >= 30 pack-years AND either current smoker (still smoking or quit < 1 year prior to pre-registration) OR former smoker (quit 1-15 years prior to pre-registration); Note: Pack years is determined by multiplying the number of packs smoked per day by the number of years smoked Eastern Cooperative Oncology Group (ECOG) performance status =< 1 Computed tomography (CT) scan of the chest done =< 6 months prior to pre-registration showing either negative findings (no nodules) or solid or part-solid nodules < 6 mm in size (consistent with < 1% probability of malignancy, Lung-Reporting and Data Systems [RADs] version 1.0) Willingness to employ adequate contraception, if applicable; Note: women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately Ability to understand and the willingness to sign a written informed consent document REGISTRATION INCLUSION CRITERIA Leukocytes (white blood cell [WBC]) >= 3,000/microliter Neutrophils (absolute neutrophil count [ANC]) >= 1,500/microliter Platelets >= 100,000/microliter Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) Note: Higher total bilirubin levels (=< 3 mg/dL) can be allowed if due to known benign liver condition, i.e. Gilbert's Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 1.5 x institutional upper limit of normal (ULN) Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal (ULN) Creatinine =< institutional upper limit of normal (ULN) Exclusion Criteria: PRE-REGISTRATION EXCLUSION CRITERIA History of any malignancy; exceptions: non-melanoma skin cancer or carcinoma in situ (CIS) of the cervix Known hepatitis B or C Receiving any other investigational agents Any prior investigational immune therapy, such as for lung cancer prevention or treatment or for CIS of the cervix Use of oral or systemic steroids or other systemic anti-immune therapy =< 90 days prior to pre-registration; Note: Use of inhaled/nasal steroids and local steroid injections for pain control are not exclusionary Known human immunodeficiency virus (HIV) Known autoimmune disease Known non-alcoholic steatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD) History of allergic reactions attributed to compounds of similar chemical or biologic composition to MUC1/Poly-ICLC Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements REGISTRATION EXCLUSION CRITERIA Any positive antinuclear antibody (ANA) titer above 1:160, even in an asymptomatic individual. Note: Weakly positive ANA defined as ANA titers up to 1:160 maximum (=< 1:160) will be acceptable in an asymptomatic individual who is otherwise eligible for the study Pregnant or breast feeding; Note: Pregnant women are excluded from this study because the MUC1/Poly-ICLC vaccine may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with MUC1/Poly-ICLC vaccine, breastfeeding should be discontinued if the mother is treated with the vaccine

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prevention (MUC1 peptide-Poly-ICLC vaccine)<br>Patients receive MUC1 peptide-Poly-ICLC vaccine SC at weeks 0, 2, and 10. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Biological: MUC1 Peptide-Poly-ICLC Vaccine<br>* Given SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Immunogenicity of the MUC1 Vaccine | Will be evaluated by monitoring changes in IgG anti-MUC1 antibody titer ratio; defined as t12/t0, where t0 is the initial titer measured prior to vaccination, and t12 is the final titer drawn at 12 weeks. A titer ratio of >= 2 will be considered a positive response. | At week 12 | 
| Count of Patients Experiencing 1 or More Grade 3+ Adverse Events at Least Possibly Related to Treatment | Will be assessed according to National Cancer Institute Common Toxicity Criteria 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. In addition, the number and severity of adverse events will be tabulated and summarized across all grades. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Smoking Status on Vaccine Response | To explore potential differences, if any, in the immunogenicity of the vaccine (as assessed at week 12 by the IgG anti-MUC1 antibody titer ratio) in current vs. former smokers. | 12 weeks | 
| Pre-Vaccination Levels Versus Post-Vaccination Levels of Circulating Myeloid Derived Suppressor Cells (MDSC) | Will correlate with the ability to respond to the vaccine. Will summarize the data using descriptive statistics and graphical methods (i.e. boxplots, scatter plots, etc.). For continuous MDSC data versus response data, will use t-tests or Wilcoxon Rank-Sum tests (for non-normal data). | 12 weeks |