A Prevention Trial of Canakinumab in Subjects at High Risk for Lung Cancer

NCT05725343 | Terminated Phase 3

• 1 other identifier: IRFMN-LUNG-8287
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 6

Brief Summary

Randomized phase III, double-blind, placebo-controlled, multicenter clinical trial.

Conditions

Lung Cancer

Keywords

Lung cancer; Prevention; Canakinumab

Outcome Measures

Primary Outcomes (1)

• Time To Lung Cancer

  TTLC will be measured from the date of randomization up to the date of lung cancer or, for subjects free from disease, the date of last contact.

  date of randomization up to the date of lung cancer or, for subjects free from disease, the date of last contact, up to 48 months

Secondary Outcomes (5)

• Time to Lung cancer death

  date of randomization, up to 48 months

• Overall Survival (OS)

  date of randomization, up to 48 months

• cancer mortality

  date of randomization, up to 48 months

• shrinkage of non-solid nodules

  date of randomization, up to 48 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  date of randomization, up to 48 months

Study Arms (2)

Canakinumab

EXPERIMENTAL

Eligible subjects will be randomized in a 3:2 ratio to receive either canakinumab s.c. at 200 mg or placebo every two months.

Drug: Canakinumab

Placebo

PLACEBO COMPARATOR

Eligible subjects will be randomized in a 3:2 ratio to receive either canakinumab s.c. at 200 mg or placebo every two months.

Drug: Placebo

Interventions

Canakinumab DRUG

Canakinumabwill be administered up to three years, or until lung cancer diagnosis, unacceptable toxicity or physician/subject's decision to withdraw, whichever comes first.

Also known as: ilaris

Canakinumab

Placebo DRUG

placebo will be administered up to three years, or until lung cancer diagnosis, unacceptable toxicity or physician/subject's decision to withdraw, whichever comes first.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained prior to any screening procedures.
• Age ≥18 years and ≤75 years;
• PLCO risk \>2,5% in 6 years to undergo CT screening;
• Annual risk of lung cancer ≥3% ( 6% at 2 years or 12% at 4 years) after the baseline CT using a second risk model which includes the presence of lung nodules such as the Brock University model;
• CRP levels above 3 mg/L;
• Former smokers or current smokers participating in smoking-cessation-programs or subjects with incidental diagnosis of undetermined nodules;
• Subjects must have normal organ and bone marrow function:
• Haemoglobin ≥ 10.0 g/dL.
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
• Platelet count ≥ 100 x 109/L.
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
• Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2.5 x ULN.

You may not qualify if:

• Active infection;
• Subjects with previous diagnosis of invasive cancer in the 5 years before enrolment;
• History or evidence of tuberculosis (TB) (active or latent) infection or one of the risk factors for tuberculosis such as but not limited or exclusive to:
• History of any of the following: residence in a congregate setting (e.g. jail or prison, homeless shelter, or chronic care facility), substance abuse (e.g. injection or noninjection) health-care workers with unprotected exposure to subjects who are at high risk of TB or subjects with TB disease before the identification and correct airborne precautions of the subject
• Close contact (i.e. share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours)) with a person with active pulmonary TB disease within the last 12 months.
• Evidence of TB infection (active or latent), at Visit 1, determined by purified protein derivative (PPD) skin test and/or QuantiFERON®-TB Gold (QFT-g) assay as defined by country guidelines (refer to Determination of Tuberculosis Status, p.39).
• i. If presence of TB (active or latent) is established then treatment (according to country guidelines for TB treatment or TB treatment with immunomodulating drugs) must have been initiated or completed prior to randomization per country guidelines.
• ii. In the absence of country TB (active or latent) guidelines, the following has been demonstrated: TB has been treated adequately with antibiotics, cure can be demonstrated, and risk factors resulting in TB exposure and contracting TB have been removed (e.g. the subject does not live anymore in high TB exposure setting).
• Subjects with suspected or proven immunocompromised state, including (a) those with evidence of Human Immunodeficiency Virus (HIV) infection; subjects on anti-retroviral therapy are excluded (b) those with any other medical condition which in the opinion of the investigator places the subject at unacceptable risk for participation in immunomodulatory therapy; or (c) those requiring systemic or local treatment with any immune modulating agent in doses with systemic effects e.g. high dose oral or intravenous steroids (\> 20 mg prednisone orally daily for \> 30 days, \> 5 mg prednisone orally daily or equivalent dose of intravenous steroid) or high dose methotrexate (\> 15 mg weekly). Topical, inhaled, local steroid use in doses that are not considered to cause systemic effects are permitted.
• History or current diagnosis of cardiac disease, including any of the following:
• recent myocardial infarction or coronary artery bypass graft (CABG) surgery within last 6 months,
• uncontrolled congestive heart failure,
• unstable angina (within last 6 months),
• clinically significant (symptomatic) cardiac arrhythmias.
• Known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (positive or indeterminate central laboratory results).

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (6)

Istituto Clinico Humanitas Rozzano

Rozzano, Milano, Italy, Italy

Location

Ente Ospedaliero Ospedali Galliera

Genova, Italy

Location

Ospedale San Martino

Genova, Italy

Location

IRST Meldola

Meldola, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

canakinumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Andrea De Censi

  Ospedali Galliera di Genova

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Eligible subjects will be randomized in a 3:2 ratio to receive either canakinumab s.c. at 200 mg or placebo every two months.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible subjects will be randomized in a 3:2 ratio to receive either canakinumab s.c. at 200 mg or placebo every two months.

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: February 13, 2023
• Study Start: February 3, 2022
• Primary Completion: April 3, 2022
• Study Completion: September 21, 2022
• Last Updated: February 13, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6)