We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Brief Title: Study of Efficacy and Safety of Canakinumab as Adjuvant Therapy in Adult Subjects With Stages AJCC/UICC v. 8 II-IIIA and IIIB (T>5cm N2) Completely Resected Non-small Cell Lung Cancer Acronym: CANOPY-A (Canopy-A)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03447769
Recruitment Status : Active, not recruiting
First Posted : February 27, 2018
Last Update Posted : July 27, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE February 19, 2018
First Posted Date  ICMJE February 27, 2018
Last Update Posted Date July 27, 2022
Actual Study Start Date  ICMJE March 16, 2018
Estimated Primary Completion Date August 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2022)
Disease free survival (DFS) by local investigator [ Time Frame: Up to approximately 5 years ]
DFS is the time from the date of randomization to the date of the first documented NSCLC disease recurrence as assessed by local investigator radiologically or death due to any cause.
Original Primary Outcome Measures  ICMJE
 (submitted: February 21, 2018)
Disease Free Survival (DFS) by local investigator [ Time Frame: up to 5 years ]
DFS will be assessed from the time from the date of randomization to the date of the first documented disease recurrence as assessed by local investigator radiologically or death due to any cause.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2022)
  • Overall Survival (OS) [ Time Frame: Up to approximately 5 years ]
    Overall Survival (OS) is the time from the date of randomization to the date of death due to any cause.
  • Disease free survival (DFS) by local investigator in PD-L1 subgroups [ Time Frame: Up to approximately 5 years ]
    DFS is the time from the date of randomization to the date of the first documented NSCLC disease recurrence as assessed by local investigator radiologically or death due to any cause. DFS analysis will be performed by programmed cell death-ligand 1 (PD-L1) status (positive, negative) where a positive status is defined as having ≥ 1% expression and a negative status is defined as having < 1% expression.
  • Disease free survival (DFS) by local investigator in CD8 subgroups [ Time Frame: Up to approximately 5 years ]
    DFS is the time from the date of randomization to the date of the first documented NSCLC disease recurrence as assessed by local investigator radiologically or death due to any cause. DFS analysis will be performed by CD8 subgroups with the median and quartiles of baseline CD8 expression as cut-offs.
  • Overall Survival (OS) by local investigator in PD-L1 subgroups [ Time Frame: up to approximately 5 years ]
    Overall Survival (OS) is the time from the date of randomization to the date of death due to any cause. OS analysis will be performed by programmed cell death-ligand 1 (PD-L1) status (positive, negative) where a positive status is defined as having ≥ 1% expression and a negative status is defined as having < 1% expression.
  • Overall Survival (OS) by local investigator in CD8 subgroups [ Time Frame: up to approximately 5 years ]
    Overall Survival (OS) is the time from the date of randomization to the date of death due to any cause. OS analysis will be performed by CD8 subgroups with the median and quartiles of baseline CD8 expression as cut-offs.
  • Lung Cancer Specific Survival (LCSS) [ Time Frame: up to approximately 5 years ]
    LCSS is defined as the time from date of randomization to the date of death due to lung cancer.
  • Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of canakinumab [ Time Frame: Up to approximately 5 years ]
    To characterize the pharmacokinetics of canakinumab therapy. AUClast will be calculated from serum concentration-time data.
  • Maximum Observed Plasma Concentration (Cmax) of canakinumab [ Time Frame: Up to approximately 5 years ]
    To characterize the pharmacokinetics of canakinumab therapy. Cmax will be calculated from serum concentration-time data.
  • Trough Concentration (Cmin) of canakinumab [ Time Frame: Up to approximately 5 years ]
    To characterize the pharmacokinetics of canakinumab therapy. Cmin will be calculated from serum concentration-time data.
  • Anti-drug Antibody (ADA) prevalence at baseline [ Time Frame: Baseline ]
    Immunogenicity to canakinumab prior to canakinumab exposure. ADA prevalence at baseline wil be calculated as the proportion of participants who had an ADA positive result at baseline
  • Anti-drug Antibody (ADA) incidence [ Time Frame: Up to approximately 5 years ]
    ADA incidence on treatment will be calculated as the proportion of participants who were treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
  • Time to definitive 10 point deterioration symptom scores of pain,cough and dyspnea per EORTC QLQ-LC13 questionnaire [ Time Frame: Up to approximately 5 years ]
    The Lung Cancer module of the EORTC's quality of life questionnaire (EORTC QLQ-LC13) is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The lung cancer module incorporates one multi-item scale to assess dyspnea, and 9 single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All of the domain scores range from 0 to 100. A high score indicates a high level of symptoms. The time to definitive 10 point deterioration symptom scores of pain, cough and dyspnea is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the EORTC QLQ-LC13 symptom score with no later change below this thereshold or death due to any cause, whichever occurs earlier
  • Time to definitive 10 point deterioration of global health status/QoL, shortness of breath and pain per EORTC QLQ-C30 questionnaire [ Time Frame: Up to approximately 5 years ]
    The EORTC QLQ-C30 is a questionnaire developed to assess the health-related quality of life of cancer participants. It assesses 15 domains consisting of 5 functional domains (physical, role, emotional, cognitive, social) and 9 symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global health status/quality of life (QoL) scale. All of the domain scores range from 0 to 100. A high score for a functional scale indicates a high and healthy level of functioning but a high score for a symptom scale indicates a high level of symptoms. The time to definitive 10 point deterioration of global health status/QoL, shortness of breath and pain is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the EORTC QLQ-C30 score with no later change below this threshold or death due to any cause, whichever occurs earlier.
  • Time to first 10 point deterioration for symptom scores of pain, cough and dyspnea per EORTC QLQ-LC13 questionnaire [ Time Frame: Up to approximately 5 years ]
    The Lung Cancer module of the EORTC's quality of life questionnaire (EORTC QLQ-LC13) is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The lung cancer module incorporates one multi-item scale to assess dyspnea, and 9 single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All of the domain scores range from 0 to 100. A high score indicates a high level of symptoms. The time to first 10 point deterioration symptom scores of pain, cough and dyspnea is defined as the time from the date of randomization to the first onset of at least 10 points absolute increase from baseline (worsening) in symptoms scores or death due to any cause, whichever occurs earlier.
  • Time to first 10 point deterioration of global health status/QoL, shortness of breath and pain per EORTC QLQ-C30 questionnaire [ Time Frame: Up to approximately 5 years ]
    The EORTC QLQ-C30 is a questionnaire developed to assess the health-related quality of life of cancer participants. It assesses 15 domains consisting of 5 functional domains (physical, role, emotional, cognitive, social) and 9 symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global health status/quality of life (QoL) scale. All of the domain scores range from 0 to 100. A high score for a functional scale indicates a high and healthy level of functioning but a high score for a symptom scale indicates a high level of symptoms. The time to first 10 point deterioration of global health status/QoL, shortness of breath and pain scores is defined as the time from the date of randomization to the first onset of at least 10 points absolute increase from baseline (worsening) in symptoms scores or death due to any cause, whichever occurs earlier.
  • Utility scores of the EQ-5D-5L [ Time Frame: Up to approximately 5 years ]
    EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2018)
  • Overall Survival (OS) [ Time Frame: up to 5 years ]
    Overall Survival (OS) is the time from the date of randomization to the date of death due to any cause.
  • Lung Cancer Specific Survival (LCSS) [ Time Frame: up to 5 years ]
    To compare lung cancer specific survival in the canakinumab arm versus placebo arm
  • Serum concentration-time profiles of canakinumab and appropriate individual PK parameters based on population PK model [ Time Frame: up to 5 years ]
    To characterize the pharmacokinetics of canakinumab therapy
  • Serum concentrations of anti-canakinumab antibodies [ Time Frame: up to 5 years ]
    To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of canakinumab
  • Time to definitive 10 point deterioration symptom scores of pain,cough and dyspnea per QLQ-LC13 questionnaire [ Time Frame: up to 5 years ]
    To assess the effect of canakinumab versus placebo on PROs (EORTC QLQC30 with QLQ-LC13 incorporated and EQ-5D) including functioning and health related quality of life
  • Time to definitive deterioration in global health status/QoL, shortness of breath and pain per QLQ-C30 together with [ Time Frame: up to 5 years ]
    To assess the effect of canakinumab versus placebo on PROs (EORTC QLQC30 with QLQ-LC13 incorporated and EQ-5D) including functioning and health related quality of life
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brief Title: Study of Efficacy and Safety of Canakinumab as Adjuvant Therapy in Adult Subjects With Stages AJCC/UICC v. 8 II-IIIA and IIIB (T>5cm N2) Completely Resected Non-small Cell Lung Cancer Acronym: CANOPY-A
Official Title  ICMJE A Phase III, Multicenter, Randomized, Double Blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Canakinumab Versus Placebo as Adjuvant Therapy in Adult Subjects With Stages AJCC/UICC v. 8 II -IIIA and IIIB (T>5cm N2) Completely Resected (R0) Non-small Cell Lung Cancer (NSCLC)
Brief Summary The primary purpose of the study is to compare the efficacy and safety of canakinumab versus placebo as adjuvant therapy in adult subjects with stages AJCC/UICC v. 8 II -IIIA and the subset of IIIB (T>5cm N2 disease) completely resected (R0) non-small cell lung cancer (NSCLC).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Canakinumab
    Canakinumab will be administered periodically for approximately 54 weeks.
    Other Name: ACZ885
  • Drug: Placebo
    Placebo will be administered periodically for approximately 54 weeks.
Study Arms  ICMJE
  • Experimental: canakinumab
    Participants will receive canakinumab for 18 cycles (approximately 54 weeks).
    Intervention: Drug: Canakinumab
  • Placebo Comparator: Placebo
    Participants will receive canakinumab placebo for 18 cycles (approximately 54 weeks).
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 29, 2022)
1382
Original Estimated Enrollment  ICMJE
 (submitted: February 21, 2018)
1500
Estimated Study Completion Date  ICMJE December 10, 2026
Estimated Primary Completion Date August 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have completely resected (R0) NSCLC AJCC/UICC v. 8 stage IIA-IIIA and IIIB (N2 disease only) OR have NSCLC Stage IIA-IIIA, IIIB (N2 disease only) and are candidates for complete resection surgery
  • Cisplatin-based chemotherapy is mandatory for all subjects (Exception: In subjects with stage IIA disease with no nodal involvement, cisplatin-based chemotherapy can be administered if recommended by the treating physician). When required, a minimum of two cycles of cisplatin-based chemotherapy is mandatory, after which additional therapies can be given based upon local clinical practice and/or guidelines. Typically, chemotherapy is initiated within 60 days of surgery.
  • Must have recovered from all toxicities related to prior systemic therapy to grade ≤ 1 (CTCAE v 4.03). Exception to this criterion: subjects with any grade of alopecia and grade 2 or less neuropathy are allowed to enter the study
  • Have ECOG performance status (PS) of 0 or 1

Exclusion Criteria:

  • Have unresectable or metastatic disease, positive microscopic margins on the pathology report, and/or gross disease remaining at the time of surgery
  • Have received any neoadjuvant therapy
  • Presence or history of a malignant disease, other than the resected NSCLC, that has been diagnosed and/or required therapy within the past 3 years Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, completely resected carcinoma in situ of any type and hormonal maintenance for breast and prostate cancer > 3 years.
  • Have a history of current diagnosis of cardiac disease
  • Have uncontrolled diabetes
  • Have known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (positive or indeterminate central laboratory results)
  • Subjects must be evaluated for tuberculosis as per local treatment guidelines or clinical practice. Subjects with active tuberculosis are not eligible.
  • Have suspected or proven immunocompromised state as described in the protocol
  • Had Live and attenuated vaccination within 3 months prior to first dose of study drug (e.g. MMR, Yellow Fever, Rotavirus, Smallpox, etc.).

Other inclusion/exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Austria,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Czechia,   France,   Georgia,   Germany,   Greece,   Hong Kong,   Hungary,   Iceland,   India,   Israel,   Italy,   Japan,   Jordan,   Korea, Republic of,   Lebanon,   Malaysia,   Norway,   Panama,   Peru,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   Slovenia,   Spain,   Switzerland,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States,   Vietnam
Removed Location Countries Australia,   Guatemala,   Ireland,   Mexico,   South Africa
 
Administrative Information
NCT Number  ICMJE NCT03447769
Other Study ID Numbers  ICMJE CACZ885T2301
2017-004011-39 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data will be available according to the process described on www.clinicalstudydatarequest.com.

Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP