Etude : NIRVANA-Lung /



ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.


Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : NIRVANA-Lung

Nom :

Traitement : Métastasique ou localement avancé

Type d'étude : Ciblage moléculaire / Innovation thérapeutique

Dernière MÀJ : 06/08/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : PD-(L)1 inhibitors with concurrent irradiation at varied tumour sites in advanced non-small cell lung cancer

Spécialité : Organes respiratoires et intrathoraciques
Localisation : C34 - Tumeur maligne des bronches et du poumon
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : 2 treatment arms:
- Experimental: Anti-PD(L) 1 + Radiotherapy
In the experimental arm, patient will receive the same treatment as the control arm in addition with conformal 3D radiotherapy (3D-CRT) or stereotactic ablative radiotherapy (SABR) that will be delivered 15 days after the beginning of immunotherapy using photons/electrons with standard field encompassing tumour.
Irradiation technique (3D-CRT or SABR) will be at physician discretion. Ideally, oligometastatic patient (defined by the presence of less than 6 metastases) should be treated with SABR and non-oligometastatic patient should be treated with 3D-CRT.
Radiotherapy will be delivered at least a dose of 18 Gy in 3 X 6 Gy for 3D-CRT. Irradiated tumor size will be ≤5 cm (GTV < 65 mL sphere); partial tumor irradiation should be delivered if larger tumor size while respecting dose constraints.

- Active Comparator: Anti-PD(L) 1
Anti-PD-(L)1 will be administered as per standard of care:
-> The anti-PD-1 antibody nivolumab will be administered at a dose of 3 mg/kg every 2 weeks.
-> The anti-PD-1 antibody pembrolizumab will be administered at a dose of 200 mg (1st line) or 2 mg/kg (2nd line) every 3 weeks.
-> The anti-PD-L1 antibody atezolizumab will be administered at a dose of 1 200 mg every 3 weeks.
Immunotherapy treatment may be continued as long as patient is experiencing clinical benefit, as assessed by an investigator, in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression after an integrated assessment of radiographic data, biopsy results (if available) and clinical status.

Phase : III

Stade : Localement avancé à Métastatique

1, 2
Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Patient must have signed a written informed consent form prior to any study specific procedures.
- Histologically or cytologically confirmed advanced (stage IIIB/IIIC/IV), squamous or non-squamous NSCLC.
- Availability of tumoral PD-L1 status if pembrolizumab used (for the other drugs if possible tumoral PD-L1 status or tumor sample to assess it).
- First-line treatment only: NSCLC patients eligible for treatment with pembrolizumab according to the European Marketing Authorisation as a first line:
-> no EGFR, ALK, or ROS-1 positive tumour mutations,
-> Tumoral expression of PD-L1 ≥50%.
- Second (third)-line treatment: NSCLC patients eligible for treatment with a PD-1 or PD-L1 antagonist according to the European Marketing Authorisation as a second line:
-> Previous treatment with chemotherapy and/or targeted treatment,
-> Patients with EGFR, ALK, or ROS-1 positive tumour mutations should also have received targeted therapy before receiving nivolumab, pembrolizumab or atezolizumab,
-> PD-L1 >1% for patients receiving pembrolizumab; any tumoral PD-L1 status for those receiving nivolumab or atezolizumab.
- Second line treatment: non-radically treatable stage IIIB/C or IV disease that has progressed on or after platinum-based chemotherapy and/or targeted therapy (targeting EGFR mutation or ALK translocation or ROS-1 translocation)
- Patient ≥18 and ≤80 years of age.
- ECOG performance status 0 - 1.
- Life expectancy >3 months.
- Measurable lesion as assessed by RECIST version 1.1.
- Metastases eligible for 3 dimensional conventional radiotherapy (3D-CRT) or stereotactic ablative radiotherapy (SABR) in terms of dose constraints at organ at risk (according to QUANTEC review).
- Patients must have adequate organ function defined by the following laboratory results obtained within 14 days prior to the first study treatment:
-> absolute neutrophil count of ≥1 500 /mm³,
-> platelets ≥ 100 000/mm³,
-> haemoglobin >9 g/dL (transfusions allowed),
-> creatinine clearance >30 mL/min,
-> bilirubin ≤1.5 X upper limit of normal (ULN) (unless Gilbert where 3 x ULN is permitted),
-> serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN (unless documented liver metastasis where ≤5 x ULN is permitted),
-> Alkaline phosphatase (ALP) ≤2.5 x ULN (unless documented bone or liver metastasis where ≤5 x ULN is permitted),
-> INR , PT, PTT ≤1.5 x ULN (unless the subject is receiving anticoagulant therapy).
- Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 6 months after completing treatment/therapy.
- Patients affiliated to the social security system.
-Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits, and examinations including follow-up.

Critères de non-inclusion : - Patient with targetable tumor mutations, activating EGFR mutations, ROS-1 translocation or ALK translocation.
Note: documentation of these mutation for non-squamous histology is mandatory as standard of care.
- Stage IIIB/IIIC NSCLC patient eligible to curative (thoracic radiotherapy or surgery) treatments in first line treatment.
- Prior therapy with T-cell costimulation or checkpoint-targeted agents.
- Clinical need of radiotherapy (e.g.: whole brain irradiation, painful metastasis, bleeding, compressive metastases).
- Irradiation within 2 months before inclusion.
- Leptomeningeal carcinomatosis, or metastases with indistinct borders making targeting not feasible.
- Patient with evidence of active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patient with brain metastasis can be included if asymptomatic and not requiring steroids.
- Metastases located within 3 cm of the previously irradiated structures (EQD2doses):
-> Spinal cord previously irradiated to >40 Gy,
-> Brachial plexus previously irradiated to >50 Gy,
-> Small intestine, large intestine, or stomach previously irradiated to >45 Gy,
-> Brainstem previously irradiated to >50 Gy,
-> Lung previously irradiated with prior V20Gy >30%.
- Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, psoriasis.
- Symptomatic interstitial lung disease.
- Systemic immunosuppression or systemic immunosuppressive medicinal products within 2 weeks prior to study entry.
- Concomitant treatment with steroids (equivalent dose of prednisone >10 mg/kg) treatment: otherwise it has to be stopped 7 days before inclusion.
- Prior invasive malignancy within the past 2 years (except non-melanomatous skin cancer non-invasive carcinoma in-situ of the breast, oral cavity, bladder or cervix).
- Known Acquired Immune Deficiency Syndrome (AIDS) or severe uncontrolled co-morbidity.
- Active hepatitis B or C.
- Patient who was administered a live, attenuated vaccine within 28 days prior to enrolment.
- Patient with any other disease or illness which requires hospitalisation or is incompatible with the study treatment are not eligible. Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study.
- Patient who have taken any investigational medicinal product or have used an investigational device within 30 days of inclusion.
- Pregnant or breast feeding woman.
- Person deprived of their liberty or under protective custody or guardianship.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03774732
Promoteur :
UNICANCER
Type de sponsor : Institutionnel
75654 Paris Cedex 13 - 75654 Paris Cedex 13
75001 PARIS 01

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre François BACLESSE - 3 avenue du Général Harris - 14000 CAEN

Investigateur :
Radj GERVAIS

TEC / ARC / IDE :
Karim HAMOND
k.hamond@
baclesse.unicancer.fr

Ouverture de l'essai : OUVERT

MAJ : 14/05/2019

Centre investigateur :
CHU de Caen - Avenue de la Côte de Nacre - 14033 Caen Cedex - 14000 CAEN

Investigateur :
Jeannick MADELAINE

TEC / ARC / IDE :
Vincent LEON
leon-v@chu-caen.fr

Ouverture de l'essai : OUVERT

MAJ : 14/05/2019