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

• ClinicalTrials.gov Identifier: NCT03300817
• Recruitment Status: Active, not recruiting
• First Posted: October 4, 2017
• Last Update Posted: February 25, 2022
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: October 3, 2017
• First Posted Date: October 4, 2017
• Last Update Posted Date: February 25, 2022
• Actual Study Start Date: December 27, 2017
• Actual Primary Completion Date: September 23, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 1, 2019)

• Immunogenicity of the MUC1 vaccine [ Time Frame: At week 12 ]
  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.
• Incidence of adverse events [ Time Frame: Up to week 24 ]
  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.

Original Primary Outcome Measures (submitted: October 3, 2017)

• Immunogenicity of the MUC1 vaccine [ Time Frame: At week 12 ]
  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.
• Incidence of adverse events according to National Cancer Institute Common Toxicity Criteria version 4.0 [ Time Frame: Up to week 24 ]
  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.

Current Secondary Outcome Measures (submitted: October 3, 2017)

• Differences in the immunogenicity of the vaccine [ Time Frame: Up to week 24 ]
• Pre-vaccination levels versus post-vaccination levels of circulating myeloid derived suppressor cells (MDSC) [ Time Frame: Up to week 12 ]
  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). For the associations of 2 continuous variables, will use linear regression, the correlation coefficient, and scatter plots.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: March 2, 2018)

• Chronic obstructive pulmonary disease (COPD) status [ Time Frame: Up to week 24 ]
  Will explore the relationship between COPD status at pre-registration and immune response in current versus former smokers. In individuals with COPD, the severity of airflow obstruction will be measured by the pulmonary function tests as per the GOLD classification.
• Changes in immunogenicity in individuals with chronic obstructive pulmonary disease (COPD) [ Time Frame: Baseline up to week 24 ]
  Will explore whether or not changes in immunogenicity in individuals with COPD corresponds to different circulating MDSC levels.
• Impact of the MUC1/Poly-ICLC vaccine on inflammation-related high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) [ Time Frame: Up to week 24 ]
• Ability to successfully vaccinate with MUC1/Poly-ICLC vaccine depending on baseline high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels [ Time Frame: Up to week 24 ]

Original Other Pre-specified Outcome Measures (submitted: October 3, 2017)

• Ability to successfully vaccinate with MUC1/Poly-ICLC vaccine depending on baseline high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels [ Time Frame: Up to week 24 ]
• Changes in immunogenicity in individuals with chronic obstructive pulmonary disease (COPD) [ Time Frame: Baseline up to week 24 ]
  Will explore whether or not changes in immunogenicity in individuals with COPD corresponds to different circulating MDSC levels.
• Chronic obstructive pulmonary disease (COPD) status [ Time Frame: Up to week 24 ]
  Will explore the relationship between COPD status at pre-registration and immune response in current versus former smokers. In individuals with COPD, the severity of airflow obstruction will be measured by the pulmonary function tests as per the GOLD classification.
• Impact of the MUC1/Poly-ICLC vaccine on inflammation-related high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) [ Time Frame: Up to week 24 ]

Descriptive Information

• Brief Title: MUC1 Vaccine in Preventing Lung Cancer in Current and Former Smokers at High Risk for Lung Cancer
• Official Title: A Pilot Study of MUC1 Vaccine in Current and Former Smokers at High Risk for Lung Cancer
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Lung Carcinoma

Intervention

• Other: Laboratory Biomarker Analysis
  Correlative studies
• Biological: MUC1 Peptide-Poly-ICLC Vaccine
  Given SC

Study Arms

Experimental: Prevention (MUC1 peptide-Poly-ICLC vaccine)

Patients receive MUC1 peptide-Poly-ICLC vaccine SC at weeks 0, 2, and 10.

Interventions:

• Other: Laboratory Biomarker Analysis
• Biological: MUC1 Peptide-Poly-ICLC Vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 3, 2017): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 1, 2022
• Actual Primary Completion Date: September 23, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03300817
• Other Study ID Numbers: NCI-2017-01781; NCI-2017-01781 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); N01-CN-2012-00042; MAY2016-08-01 ( Other Identifier: Mayo Clinic in Rochester ); MAY2016-08-01 ( Other Identifier: DCP ); N01CN00042 ( U.S. NIH Grant/Contract ); P30CA015083 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Cancer Institute (NCI)
• Original Responsible Party: Same as current
• Current Study Sponsor: National Cancer Institute (NCI)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Arjun Pennathur; Mayo Clinic in Rochester

• PRS Account: National Cancer Institute (NCI)
• Verification Date: February 2022