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

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2017-004011-39-ES
• Date of registration: 02/03/2018
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmacéutica, S.A.
• Public 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
• Scientific title: 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)
• Date of first enrolment: 05/04/2018
• Target sample size: 1500
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004011-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Costa Rica, Egypt, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Jordan, Korea, Democratic People's Republic of, Lebanon, Malaysia, Mexico, Netherlands, New Zealand, Norway, Oman, Panama, Peru, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Trial Monitoring Organization (TMo)
• Affiliation: Novartis Farmacéutica, S.A.

• Name: Trial Monitoring Organization (TMo)
• Affiliation: Novartis Farmacéutica, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for inclusion in this study have to meet all of the following criteria at the time of screening:

1.Written informed consent must be obtained prior to any screening procedures.
2.Age = 18 years
3.Completely resected (R0) AJCC/UICC v. 8 stage IIA with T>4 to 5 cm and N0 (no nodal involvement), if no adjuvant chemotherapy is given, must be randomized within 70 days post complete surgical resection of their NSCLC.
4.Subjects with completely resected (R0) AJCC/UICC v. 8 stages IIA, IIB, IIIA or IIIB (T>5 cm N2) disease NSCLC, who received chemotherapy and no radiation therapy must be randomized within 182 days post complete surgical resection of their NSCLC.
5.Subjects with completely resected (R0) AJCC/UICC v. 8 stage IIIA N2 (T =5 cm only) or stage IIIB (T> 5cm N2) disease who receive radiation therapy along with chemotherapy detailed in inclusion criterion 6, must be randomized within 259 days of complete surgical resection.
6.Adjuvant chemotherapy is mandatory with stage AJCC/UICC v. 8 stage II-IIIA and stage IIIB (T>5cm N2) disease for 4 cycles (21 or 28 day cycles) as per local/national guidelines (except if not tolerated, in which case at least 2 cycles of adjuvant chemotherapy are required).
•Chemotherapy must be cisplatin based. Combination partners may include vinorelbine, etoposide, docetaxel or gemcitabine for any histology. For non-squamous carcinomas only, the combination partner may be pemetrexed.
7.Subjects 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.
8.Subjects must have adequate organ function including the following laboratory values at the screening visit:
•Absolute neutrophil count (ANC) = 1.5 x 109/L
•Platelets = 100 x 109/L
•Hemoglobin (Hgb) > 9 g/dL
•Creatinine clearance greater than 45 ml/min using Cockcroft-Gault formula
•Total bilirubin = 1.5 x ULN
•Aspartate transaminase (AST) = 3 x ULN
•Alanine transaminase (ALT) = 3 x ULN
9.ECOG performance status (PS) of 0 or 1.
10.Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 825
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 675

Exclusion criteria:
Subjects eligible for this study must not meet any of the following criteria at the time of screening:
- Subjects with unresectable or metastatic disease, positive microscopic margins on the pathology report, and/or gross disease remaining at the time of surgery.
- Subjects who received neoadjuvant chemotherapy or neoadjuvant radiotherapy.
- 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, and completely resected carcinoma in situ of any type.
- History of interstitial lung disease.
- 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 (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker).
- Thoracic radiotherapy to lung fields = 4 weeks prior to starting cycle 1 day 1 or subjects who have not recovered from radiotherapy-related toxicities. Radiation therapy is suggested, but not required to be given to subjects with completely resected (R0) AJCC/UICC v. 8 stage IIIA or IIIB with T>5cm N2 disease, subjects with N2 disease (mediastinal radiation).
- Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to randomization or who have not recovered from side effects of such procedure. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and subjects can be enrolled in the study =1 week after the procedure.
- Known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (positive or indeterminate central laboratory results).
- Subjects with a history of tuberculosis (TB) infection, active or latent, or one of the protocol-defined risk factors.
- Subjects with suspected or proven immunocompromised state as defined in the protocol.
- Live vaccination within 3 months prior to first dose of study drug.
- Prior treatment with canakinumab or drugs of a similar mechanism of action (IL-1ß inhibitor).
- History of hypersensitivity to canakinumab or drugs of a similar class.
- Subjects receiving any biologic drugs targeting the immune system (for example, TNF blockers, anakinra, rituximab, abatacept, or tocilizumab).
- Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
- Women of child-bearing potential as defined in the protocol.

Other protocol-defined exclusion criteria may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

stages AJCC/UICC v. 8 II-IIIA and IIIB (T>5cm N2) completely resected (R0) non-small cell lung cancer (NSCLC)
MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: canakinumab
Product Code: ACZ885
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2
Current Sponsor code: ACZ885
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: canakinumab
Product Code: ACZ885
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2
Current Sponsor code: ACZ885
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): DFS determined by local investigator assessment

Main Objective: The primary objective is to compare the Disease-free survival (DFS) in the canakinumab versus placebo arms as determined by local investigator assessment.

Timepoint(s) of evaluation of this end point: Two interim analyses will be performed for DFS: 1) an interim analysis (IA) for futility when approximately 196 (50%) of the 392 DFS events have been observed (expected around 27 months from the date of first patient randomized in the study). The primary intent of this IA is to determine whether there is a need to stop the study early for lack of efficacy (futility, there is no plan to stop the study for efficacy at this IA), and

2) An IA for efficacy when approximately 294 (75%) of the 392 DFS events have been observed (expected around 34 months from the date of first patient randomized in the study). The study will not be assessed for futility at the second IA.

Secondary Objective: Key secondary objective:
- To compare overall survival (OS) in the canakinumab arm versus placebo arm

Other secondary objectives:
1. To compare lung cancer specific survival in the canakinumab arm versus placebo arm
2. To characterize the safety profile of canakinumab
3. To characterize the pharmacokinetics of canakinumab therapy
4. To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of canakinumab
5. To assess the effect of canakinumab versus placebo on PROs (EORTC QLQ-C30 with QLQ-LC13 incorporated and EQ-5D) including functioning and health-related quality of life

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The study will end once the final OS analysis is performed when approximately 504 deaths are observed or when statistical significance is reached for OS analysis and the final analysis of study data is conducted. All available data from all subjects up to this cutoff date will be analyzed. If the primary analysis of DFS does not demonstrate treatment benefit, the follow-up for OS will end.

Secondary end point(s): Key secondary endpoint:
- OS

Other secondary endpoints:
1. Lung cancer specific survival (LCSS)
2. Frequency of AEs, ECGs and laboratory abnormalities
3. Serum concentration-time profiles of canakinumab and appropriate individual PK parameters based on population PK model
4. Serum concentrations of anti-canakinumab antibodies
5. Time to definitive 10 point deterioration symptom scores of pain, cough and dyspnea per QLQ-LC13 questionnaire are primary PRO variables of interest. Time to definitive deterioration in global health status/QoL, shortness of breath and pain per QLQ-C30 together with the utilities derived from EQ-5D-5L are secondary PRO variables of interest

Secondary ID(s)

CACZ885T2301

Source(s) of Monetary Support

Novartis Pharma AG