Lung Carcinoma
Conditions
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALMUC1 Peptide-Poly-ICLC Vaccine
Given SC
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Immunogenicity of the MUC1 Vaccine | 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. |
| Count of Patients Experiencing 1 or More Grade 3+ Adverse Events at Least Possibly Related to Treatment | 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Smoking Status on Vaccine Response | 12 weeks | 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. |
| Pre-Vaccination Levels Versus Post-Vaccination Levels of Circulating Myeloid Derived Suppressor Cells (MDSC) | 12 weeks | 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). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORArjun Pennathur
Mayo Clinic in Rochester
Participant flow
Recruitment details
1 patient withdrew prior to beginning treatment and has been removed from all analyses
Participants by arm
| Arm | Count |
|---|---|
| Prevention (MUC1 Peptide-Poly-ICLC Vaccine) Patients receive MUC1 peptide-Poly-ICLC vaccine SC at weeks 0, 2, and 10.
Laboratory Biomarker Analysis: Correlative studies
MUC1 Peptide-Poly-ICLC Vaccine: Given SC | 49 |
| Total | 49 |
Baseline characteristics
| Characteristic | Prevention (MUC1 Peptide-Poly-ICLC Vaccine) |
|---|---|
| Age, Continuous | 67.4 years STANDARD_DEVIATION 4.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 48 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 33 Participants |
| Smoking Status Current Smoker | 29 Participants |
| Smoking Status Former Smoker | 20 Participants |
| Weight | 83.1 kg STANDARD_DEVIATION 19.47 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 49 |
| other Total, other adverse events | 49 / 49 |
| serious Total, serious adverse events | 3 / 49 |
Outcome results
Primary
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.
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prevention (MUC1 Peptide-Poly-ICLC Vaccine) | Count of Patients Experiencing 1 or More Grade 3+ Adverse Events at Least Possibly Related to Treatment | 2 Participants |
Primary
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.
Time frame: At week 12
Population: 4 patients are excluded from this analysis because they did not receive injections at weeks 2 and 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prevention (MUC1 Peptide-Poly-ICLC Vaccine) | Number of Participants With Immunogenicity of the MUC1 Vaccine | 13.3 percentage of participants |
Secondary
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.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prevention (MUC1 Peptide-Poly-ICLC Vaccine) | Effect of Smoking Status on Vaccine Response | 4 participants that responded to vaccine |
| Former Smoker | Effect of Smoking Status on Vaccine Response | 2 participants that responded to vaccine |
Secondary
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).
Time frame: 12 weeks
Population: Only patients with available data on levels of circulating myeloid derived suppressor cells at 12 weeks are included
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prevention (MUC1 Peptide-Poly-ICLC Vaccine) | Pre-Vaccination Levels Versus Post-Vaccination Levels of Circulating Myeloid Derived Suppressor Cells (MDSC) | 13.9 percent CD33 |
| Former Smoker | Pre-Vaccination Levels Versus Post-Vaccination Levels of Circulating Myeloid Derived Suppressor Cells (MDSC) | 9.4 percent CD33 |
p-value: 0.6834Wilcoxon Rank-Sum test
Other Pre-specified
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
Other Pre-specified
Changes in Immunogenicity in Individuals With Chronic Obstructive Pulmonary Disease (COPD)
Will explore whether or not changes in immunogenicity in individuals with COPD corresponds to different circulating MDSC levels.
Time frame: Baseline up to week 12
Other Pre-specified
Chronic Obstructive Pulmonary Disease (COPD) Status
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.
Time frame: Baseline to week 12
Other Pre-specified
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