Canakinumab for the Prevention of Lung Cancer, the Can-Prevent-Lung Trial

PRIMARY OBJECTIVE:

I. To determine whether canakinumab increases regression rate of high-risk pulmonary nodules.

SECONDARY OBJECTIVES:

I. To determine whether canakinumab prolongs lung cancer-free survival. II. To determine whether canakinumab decreases the incidence of lung cancers. III. To assess the safety and tolerability of canakinumab in patients with high-risk indeterminate pulmonary nodules (IPNs).

IV. To assess quality of life by patient reported outcomes in patients treated with canakinumab.

EXPLORATORY OBJECTIVES:

I. To explore the radiographic (including radiomic features) evolution of high-risk IPNs with treatment of canakinumab and to assess their association with risks of lung cancer as well as their association with clinical benefit/toxicities in patients treated with canakinumab.

II. To explore the T-cell receptor (TCR) repertoire evolution of patients with high-risk IPNs and assess their association with risks of lung cancer as well as their association with clinical benefit/toxicities in patients treated with canakinumab.

III. To explore the evolution of serum soluble factors, such as IFN-gamma and interferon inducible factors (such as CXCL9 and CXCL10), IL-12, TNFalpha, IL-10, TGF-beta, VEGF, IL-6, IL-8, IL-17, IL-18, C-reactive protein etc.) and assess their association with risks of lung cancer as well as their association with clinical benefit/toxicities in patients treated with canakinumab.

OUTLINE:

Patients receive canakinumab subcutaneously (SC) on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study, patients are followed up for 30 days and at 6, 12, and 24 weeks.

Inclusion criteria

• The participant (or legally authorized representative if applicable) provides written informed consent for the trial
• Participants are eligible to be included in the study if one of the following criteria applies:

• Patients with no history of lung cancer, who have persistent IPNs (on two computed tomography [CT] scans at least 3 months apart with no evidence of shrinkage or regression) detected by low dose computed tomography [LDCT]-guided lung cancer screening or imaging studies for other reasons (incidentalomas) with 10-30% cancer probability by Brock University cancer prediction equation as following
• Patients with no history of lung cancer, who have persistent IPNs (on two CT scans at least 3 months apart with no evidence of shrinkage or regression) detected by LDCT-guided lung cancer screening or imaging studies for other reasons (incidentalomas) with > 30% cancer probability by Brock University cancer prediction equation as following, but biopsy showed no clear evidence of malignancy
• Patients with history of stage I-III non-small cell lung cancer (NSCLC), who have completed treatment with curative intent, who have persistent IPNs (on two CT scans at least 3 months apart with no evidence of shrinkage or regression) with 5-30% cancer probability by Brock University cancer prediction equation as following
• Patients with history of stage I-III NSCLC, who have completed treatment with curative intent, who have persistent IPNs (on two CT scans at least 3 months apart with no evidence of shrinkage or regression) with > 30% cancer probability by Brock University cancer prediction equation, but biopsy showed no clear evidence of malignancy
• At least 18 years of age on the day of signing informed consent
• A male participant must agree to use a contraception during the treatment period plus an additional 6months (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 6 months after study treatments with risk of genotoxicity after the last dose of study treatment
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the start of study treatment
• Absolute neutrophil count (ANC) >= 1500/uL (collected within 10 days prior to the start of study treatment)
• Platelets >= 100 000/uL (collected within 10 days prior to the start of study treatment)
• Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (collected within 10 days prior to the start of study treatment)

• Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• Creatinine =< 1.5 x upper limit or normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (collected within 10 days prior to the start of study treatment)

• Creatinine clearance (CrCl) should be calculated per institutional standard
• Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (collected within 10 days prior to the start of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x ULN (collected within 10 days prior to the start of study treatment)

Exclusion criteria

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
• Has received prior therapy with an anti-IL1beta
• Has a known additional malignancy that is progressing or has required active treatment within the past year. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
• Has an active infection requiring systemic therapy
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through 6 months after the last dose of trial treatment
• Is receiving the following therapies during the screening and treatment phases (including retreatment for post-complete response relapse) of this trial: antineoplastic systemic chemotherapy or biological therapy, immunotherapy not specified by this protocol, chemotherapy not specified by this protocol, investigational agents other than canakinumab
• Has received live vaccines within 30 days prior to first dose of study treatment and while participating in the study. Examples of live vaccines include but are not limited to: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guerin (BCG) and typhoid vaccine. (Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however intranasal influenza vaccines (eg FluMist are live attenuated vaccines are not allowed)