Clinical trial NCT03300817: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Lung Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2017-10-04
Enrollment: 50
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Participants With Immunogenicity of the MUC1 Vaccine
timeFrame: At week 12
measure: Count of Patients Experiencing 1 or More Grade 3+ Adverse Events at Least Possibly Related to Treatment
timeFrame: 24 weeks
Secondary outcomes:
measure: Effect of Smoking Status on Vaccine Response
timeFrame: 12 weeks
measure: Pre-Vaccination Levels Versus Post-Vaccination Levels of Circulating Myeloid Derived Suppressor Cells (MDSC)
timeFrame: 12 weeks
Other outcomes:
measure: Chronic Obstructive Pulmonary Disease (COPD) Status
timeFrame: Baseline to week 12
measure: Changes in Immunogenicity in Individuals With Chronic Obstructive Pulmonary Disease (COPD)
timeFrame: Baseline up to week 12
measure: Impact of the MUC1/Poly-ICLC Vaccine on Inflammation-Related High Sensitivity C-Reactive Protein (hsCRP) and Interleukin-6 (IL-6)
timeFrame: Up to week 24
measure: Ability to Successfully Vaccinate With MUC1/Poly-ICLC Vaccine Depending on Baseline High Sensitivity C-Reactive Protein (hsCRP) and Interleukin-6 (IL-6) Levels
timeFrame: Up to week 24
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute (UPCI)
state: Pennsylvania
Study officials:
affiliation: Mayo Clinic in Rochester
name: Arjun Pennathur
role: PRINCIPAL_INVESTIGATOR
References: