Evaluation of Canakinumab in High-Risk Former-Smokers

NCT06038526 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-22297NCI-2023-05942
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Cigarette Smoking-Related Carcinoma; Lung Carcinoma

Outcome Measures

Primary Outcomes (3)

• Change in ASCs (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain)

  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.

  At baseline and day 77

• Change in caspase-1

  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.

  At baseline and day 77

• Change in interleukin-1 beta (IL-1beta)

  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.

  At baseline and day 77

Secondary Outcomes (4)

• Changes in immune cell composition in bronchoalveolar lavage (BAL) by mass cytometry (CyTOF)

  At baseline and day 77

• Changes in cytokines in the blood

  At baseline and day 77

• Changes in BAL

  At baseline and day 77

• Bronchoscopy for fractional concentration of exhaled nitric oxide (FeNO)

  At baseline and day 77

Study Arms (1)

Prevention (canakinumab, bronchoscopy)

EXPERIMENTAL

Patients undergo bronchoscopy over 30-60 minutes and receive canakinumab 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 CO testing on study.

Procedure: Biospecimen Collection; Procedure: Bronchoscopy; Biological: Canakinumab; Procedure: Carbon Monoxide Measurement; Other: Survey Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo buccal, nasal, and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Prevention (canakinumab, bronchoscopy)

Bronchoscopy PROCEDURE

Undergo bronchoscopy

Prevention (canakinumab, bronchoscopy)

Canakinumab BIOLOGICAL

Given SC

Also known as: ACZ885, Ilaris

Prevention (canakinumab, bronchoscopy)

Carbon Monoxide Measurement PROCEDURE

Undergo CO testing

Also known as: Carbon Monoxide, CO

Prevention (canakinumab, bronchoscopy)

Survey Administration OTHER

Ancillary studies

Prevention (canakinumab, bronchoscopy)

Eligibility Criteria

• Age: 55 Years - 73 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• Smoked tobacco or cannabis within 5 years of enrollment (target study population is former smokers)
• CO \> 8ppm (target study population is former smokers)
• History of or recent exposure to tuberculosis (TB) as documented in the electronic medical record (EMR) and/or testing (impacts risk)
• Body mass index (BMI) \> 45 (risk of unstable airway)
• Taking acetylsalicylic acid (ASA) or nonsteroidal anti-inflammatory drugs (NSAIDs) daily or most days per week (impacts biomarkers and risk)
• Concomitant diseases and life-threatening conditions (e.g., cancer or kidney, liver, immune system disorders)
• Prior diagnosis of chronic pulmonary disease (e.g., asthma with regular use of medications, chronic bronchitis, and restrictive lung disease) (impacts biomarkers and risk)
• Acute bronchitis or pneumonia within 1 year (impacts biomarkers)
• COVID-19 diagnosis or related symptoms within the last 3 months (impacts biomarkers and risk). 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 PI
• General anesthesia within 1 year (impacts biomarkers)
• Regular use of inhalant medications in the last 3 months (impacts biomarkers)
• Use of antibiotics in prior 30 days (impacts biomarkers)

Sponsors & Collaborators

• Peter Shields: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The James line

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Specimen Handling; Bronchoscopy; canakinumab; Carbon Monoxide

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Diagnostic Techniques, Respiratory System; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures; Carbon Compounds, Inorganic; Inorganic Chemicals; Gases; Oxides; Oxygen Compounds

Study Officials

• Peter G Shields, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 6, 2023
• First Posted: September 14, 2023
• Study Start: March 11, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)