Cigarette Smoking-Related Carcinoma, Lung Carcinoma
Conditions
Brief summary
This phase II trial tests the impact of canakinumab on biologic samples (buccal, nasal, and blood) from former smokers with increased risk of cancer. Canakinumab blocks the activity of a protein called interleukin-1 beta (IL-1b), an agent of the inflammatory system and is used for the treatment of different non-cancer diseases (like auto-inflammatory diseases). Giving canakinumab may block the inflammatory system and could have positive effects to reduce cancer growth.
Detailed description
PRIMARY OBJECTIVE: I. To compare baseline bronchoscopy biospecimens with samples approximately 70 days after administration of canakinumab (2 doses, approximately 14 days apart) in healthy former smokers. SECONDARY OBJECTIVE: I. Determine the impact of IL-1beta inhibition on downstream inflammatory pathways. OUTLINE: Patients undergo bronchoscopy over 30-60 minutes on day 7 and receive canakinumab subcutaneously (SC) 60 minutes and 2 weeks after the initial bronchoscopy. Patients undergo an additional bronchoscopy on day 77. Patients undergo buccal, nasal, and blood sample collection and carbon monoxide (CO testing on study).
Interventions
PROCEDUREBiospecimen Collection
Undergo buccal, nasal, and blood sample collection
PROCEDUREBronchoscopy
Undergo bronchoscopy
BIOLOGICALCanakinumab
Given SC
PROCEDURECarbon Monoxide Measurement
Undergo CO testing
OTHERSurvey Administration
Ancillary studies
Sponsors
Peter Shields
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 73 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 55-73 (age criteria aligns with Canakinumab Antiinflammatory Thrombosis Outcome Study \[CANTOS\] trial) * If female: evidence of post-menopausal status or negative urinary or serum pregnancy test (unknown impact on pregnancy). Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 6 weeks after stopping medication. Highly effective contraception methods include: Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. * Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant * Use of oral, (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasomotor symptoms). Women are considered not of a childbearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential. Women will also be considered post-menopausal if they have been amenorrhoeic for 12 months without an alter-native medical cause. The following age-specific requirements apply: * Women \>= 50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy) * Former smoker with no use in \>= 5 years prior to enrollment (targets former smoker population) * CO =\< 8ppm (targets/confirms former smoker population) * Pack-years history of \>= 30 (defined as high risk) * No unstable or significant medical conditions as determined by medical history (see
Exclusion criteria
below - to ensure safety of the subject, to minimize the effects of poor health on biomarker measures and to maximize compliance to study procedures) * C-reactive protein high-sensitivity (hsCRP) levels \>= 2 mg/L (defined as increased risk) * Negative coronavirus disease (COVID-19) test (if applicable). According to institutional standards, which may evolve throughout the study, if a subject self-reports testing positive for COVID-19, the condition should be resolved without ongoing symptoms for at least three months. If a subject tests positive before the first bronchoscopy, the subject would be placed on a wait list for at least three months and re-tested before his/her appointment; if a subject tests positive before a follow-up bronchoscopy, his/her participation will be withdrawn by the principal investigator (PI) * Able to read adequately to complete the survey and related study documents or give consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in ASCs (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain) | At baseline and day 77 | Will be assessed by a generalized linear mixed model (GLM) and will be employed with measure as the dependent variable, a main effect of baseline vs. follow-up, covariables sex and age, and a random effect for subject. |
| Change in caspase-1 | At baseline and day 77 | Will be assessed by a GLM and will be employed with measure as the dependent variable, a main effect of baseline vs. follow-up, covariables sex and age, and a random effect for subject. |
| Change in interleukin-1 beta (IL-1beta) | At baseline and day 77 | Will be assessed by a GLM and will be employed with measure as the dependent variable, a main effect of baseline vs. follow-up, covariables sex and age, and a random effect for subject. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in cytokines in the blood | At baseline and day 77 | Will be assessed by the human magnetic luminex assay on the Luminex platform and inflammatory gene expression by RNASeq. |
| Changes in immune cell composition in bronchoalveolar lavage (BAL) by mass cytometry (CyTOF) | At baseline and day 77 | Will be performed using SPADE to create a global map of cell types present across samples and how the frequency or activation state of each cell type differs between baseline vs. follow-up (single arm). Will assess batch effects and include batch as a co-variable in the models. Will be assessed by the human magnetic luminex assay on the Luminex platform and inflammatory gene expression by ribonucleic acid sequence (RNASeq). |
| Changes in BAL | At baseline and day 77 | Will be assessed by the human magnetic luminex assay on the Luminex platform and inflammatory gene expression by RNASeq. |
| Bronchoscopy for fractional concentration of exhaled nitric oxide (FeNO) | At baseline and day 77 | Will be assessed by the human magnetic luminex assay on the Luminex platform and inflammatory gene expression by RNASeq. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORPeter G Shields, MD
Ohio State University Comprehensive Cancer Center
Outcome results
None listed