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EUCTR2017-004011-39 | SNCTP000002879

Étude évaluant l’efficacité et la sécurité d’emploi du canakinumab par rapport au placebo en tant que traitement adjuvant après résection d’un cancer du poumon

Datenbasis: BASEC (Import vom 21.02.2019), WHO (Import vom 17.02.2019)
Geändert: 11.02.2019
Krankheitskategorie: Lungenkrebs, Anderer Krebs

Zusammenfassende Beschreibung der Studie (Datenquelle: BASEC)

Cette étude clinique vise à évaluer si le médicament canakinumab (ACZ885) est sûr et s’il a des effets bénéfiques comme traitement adjuvant pour empêcher la réapparition du cancer chez les personnes ayant eu un cancer bronchique non à petites cellules (CBNPC, stades II-IIIA avec T > 5 cm et N2) et ayant fait l’objet d’un traitement recommandé.

Le traitement recommandé comprend l’ablation chirurgicale complète obligatoire du cancer primaire, suivie d’une chimiothérapie (à base de cisplatine) et d’une radiothérapie (si indiquée).

Le canakinumab est un anticorps monoclonal dirigé contre l’interleukine-1β (IL-1β) humaine avec une haute affinité autorisé dans le traitement de sujets atteints de diverses maladies auto-inflammatoires. La cytokine IL-1β est considérée comme l’un des médiateurs de l’inflammation pulmonaire qui favorise le cancer du poumon. Les résultats d’une autre étude (étude CACZ885M2301, également appelée CANTOS) ont montré que le canakinumab était associé à une réduction dose-dépendante des risques de survenue de cancer du poumon et de la mortalité par cancer du poumon.

Les participants recevront le canakinumab ou un placebo (substitut de médicament factice sans substance active) comme traitement à l’étude. La probabilité d’être traité(e) soit par le canakinumab soit par le placebo est de 50% (comme à pile ou face). Une dose consistera en 2 injections sous la peau (injections sous-cutanées) avec au total 200 mg de canakinumab ou de placebo correspondant. Le traitement dans cette étude est «en double aveugle». Cela signifie que ni le patient ni le médecin de l’étude ne sait quel traitement est pris.

Environ 1’500 patients participeront à cette étude dans environ 300 centres dans le monde. L’étude devrait se terminer en 2025, mais pour les participants, elle durera environ 54 semaines de traitement à l’étude, suivies de 4 ans de suivi pour contrôler la réapparition du cancer.

Untersuchte Krankheiten (Datenquelle: BASEC)

Cette étude inclura des patients présentant un cancer bronchique non à petites cellules (CBNPC) totalement réséqué (stades II-IIIA et IIIB, selon 8e v. AJCC/UICC). Ces groupes ont été inclus pour permettre à tous les patients qui le peuvent, de parvenir à une résection complète de leur cancer présentant des marges chirurgicales négatives (statut R0). Ces patients ont un risque significatif de rechute et méritent d’être inclus dans des essais adjuvants.

Health conditions (Datenquelle: WHO)

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

Seltene Krankheit (Datenquelle: BASEC)

Nein

Untersuchte Intervention (z.B. Medikament, Therapie, Kampagne) (Datenquelle: BASEC)

Les sujets admissibles seront affectés au hasard, selon un rapport de 1:1, à l’un ou l’autre des deux bras de traitement: canakinumab 200 mg ou le placebo correspondant. Le médicament à l’étude sera injecté sous la peau le Jour 1 du Cycle 1, puis à tous les cycles (21 jours) pendant 18 cycles.

Interventions (Datenquelle: WHO)


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 milligram(s)
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 milligram(s)
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

Kriterien zur Teilnahme an der Studie (Datenquelle: BASEC)

Homme ou femme ≥ 18 ans

Sujets avec CBNPC totalement réséqué (R0) de stades II-IIIA et IIIB (T > 5 cm N2) selon 8ev. AJCC/UICC

Chimiothérapie adjuvante obligatoire (au moins 2 cycles) pour tous les sujets sauf ceux présentant une maladie de stade IIA (avec T > 4-5 cm)

Ausschlusskriterien (Datenquelle: BASEC)

Sujets présentant une maladie non résécable ou métastatique, des marges microscopiques positives sur le rapport de pathologie, et/ou un résidu macroscopique de la maladie lors de la chirurgie

Sujets ayant reçu une chimiothérapie ou une radiothérapie de support avant résection (traitement néoadjuvant)

Femmes enceintes ou allaitantes ou femmes en âge d’avoir des enfants, sauf si elles utilisent des méthodes de contraception très efficaces au cours du traitement et pendant les 130 jours qui suivent l’arrêt du traitement

Inclusion/Exclusion Criteria (Datenquelle: WHO)

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.

Weitere Angaben zur Studie im WHO-Primärregister

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004011-39

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2017-004011-39

Weitere Informationen zur Studie

Registrationsdatum der Studie

12.06.2018

Einschluss der ersten teilnehmenden Person

16.07.2018

Rekrutierungsstatus

Authorised-recruitment may be ongoing or finished

Wissenschaftlicher Titel (Datenquelle: WHO)

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)

Studientyp (Datenquelle: WHO)

Interventional clinical trial of medicinal product

Design der Studie (Datenquelle: WHO)

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 (Datenquelle: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no

Primäre Endpunkte (Datenquelle: WHO)

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

Sekundäre Endpunkte (Datenquelle: WHO)

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

Kontakt für Auskünfte (Datenquelle: WHO)

Novartis Pharma AG

Studiendurchführungsorte

Durchführungsorte in der Schweiz (Datenquelle: BASEC)

Freiburg, Genf

Durchführungsländer (Datenquelle: WHO)

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Costa Rica, Czech Republic, Democratic People's Republic of, Egypt, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Jordan, Korea, 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

Kontakt für weitere Auskünfte zur Studie

Angaben zur Kontaktperson in der Schweiz (Datenquelle: BASEC)

Janine Landolt
+41 79 500 93 56
janine.landolt@novartis.com

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

Clinical Trial Information Desk
Forum 1, Novartis Campus /  Lichtstrasse 35
Novartis Pharma AG
+41613241 111
clinicaltrial.enquiries@novartis.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Clinical Trial Information Desk
Forum 1, Novartis Campus /  Lichtstrasse 35
Novartis Pharma AG
+41613241 111
clinicaltrial.enquiries@novartis.com

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

Novartis Pharma AG

Weitere Studienidentifikationsnummern

BASEC ID (Datenquelle: BASEC)

2018-00217

Secondary ID (Datenquelle: WHO)

CACZ885T2301