Informations générales (source: ClinicalTrials.gov)
PD-1 Inhibitor and Chemotherapy With Concurrent Irradiation at Varied Tumour Sites in Advanced Non-small Cell Lung Cancer
Interventional
Phase 3
UNICANCER (Voir sur ClinicalTrials)
janvier 2018
décembre 2026
02 décembre 2025
Overall survival (OS) of patients with advanced (stage IIIB/IV) non-small-cell lung
cancer (NSCLC) remains short after the first line of treatment with a median OS of 12.2
months in non squamous NSCLC and 9.2 months in squamous NSCLC . In this setting the
programmed death 1/ligand 1 (PD-1/-L1) were targeted with nivolumab (IgG4) in advanced
squamous and nonsquamous NSCLC leading to an increase of the 1-year OS rate of
approximately 10-15% in both histologies. Nivolumab, pembrolizumab and atezolizumab are
now considered a standard of care in 2nd line advanced NSCLC and in 1st line for
pembrolizumab but but prognosis still remains poor in advanced NSCLC. Overall survival
(OS) of patients with advanced (stage III/IV) NSCLC remains limited with a median OS of
12.2 months in non-squamous NSCLC and 9.2 months in squamous NSCLC if anti-PD1 alone. It
is of around 16 months if pembrolizumab is combined with chemotherapy.
Preclinical data indicates that anti-tumor efficacy is increased when anti-PD-1/-L1 are
combined with irradiation (IR). Radiotherapy alone can elicit tumor cell death which can
increase tumor antigen in the blood stream, favoring recognition by the immune system and
its activation against tumor cells outside of the radiation field (="abscopal effect").
IR may also reverse acquired resistance to PD-1 blockade immunotherapy by limiting T-cell
exhaustion.
Because of these preclinical and clinical data several studies analysing the combination
of IR and anti-PD1 in NSCLC are ongoing. Among them, two studies are testing the
administration of IR and nivolumab in stage III NSCLC: the NCT02768558 phase III trial
(RTOG), and the NCT02434081 phase II trial (ETOP). Antonia et al [2017] tested the use of
anti-PD-L1 after chemoradiotherapy in unresectable stage III NSCLC. Median time to
distant metastasis was increased (23.2 months vs. 14.6 months, p<0.001). An increase of
OS is consequently expected.
However, no study involving concurrent RT and pembrolizumab combined with chemotherapy in
advanced NSCLC is ongoing, which is the purpose of the present study, NIRVANA-Lung.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CHI DE CRETEIL | Isabelle MONNET | 02/07/2025 13:10:01 | Contacter | ||
| CLCC INSTITUT CURIE | 04/06/2024 14:01:28 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Antonin LEVY | 18/03/2024 11:06:01 | Contacter | ||
| CLCC RENE HUGUENIN INSTITUT CURIE | 10/04/2025 13:11:59 | Contact (sur clinicalTrials) | |||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital La Pitié-Salpêtrière | Nicolas MEILLAN, MD | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Tenon | Contact (sur clinicalTrials) | ||||
| CHI DE CRETEIL | Isabelle MONNET, MD | Contact (sur clinicalTrials) | |||
| FONDATION HOPITAL SAINT-JOSEPH | Charles NALTET, MD | Contact (sur clinicalTrials) | |||
| IFSI DE L'HÔPITAL BICÊTRE | Andrei SEFERIAN, MD | Contact (sur clinicalTrials) | |||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre de cancérologie du grand Montpellier-Clinique Clementville - Montpellier 2992166 - France | Emmanuel BEGUIER, MD | Contact (sur clinicalTrials) | |||
| Centre de radiothérapie et de cancérologie de Blois - La Chaussée-Saint-Victor 3010092 - France | Contact (sur clinicalTrials) | ||||
| Centre Frédéric JOLIOT - Rouen 2982652 - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier des Pays de Morlaix - Morlaix 2991772 - France | Karim AMRANE, MD | Contact (sur clinicalTrials) | |||
| Centre Jean Perrin - Clermont-Ferrand 3024635 - France | Pascale DUBRAY LONGERAS | Contact (sur clinicalTrials) | |||
| Centre Marie Curie - Arras 3036784 - France | Contact (sur clinicalTrials) | ||||
| Centre Marie Curie - Valence 2971053 - France | Emilie BONNET, MD | Contact (sur clinicalTrials) | |||
| Centre Paul Strauss - Strasbourg 2973783 - France | Roland SCHOTT, MD | Contact (sur clinicalTrials) | |||
| Centre Pierre Curie - Beuvry 3032903 - France | Contact (sur clinicalTrials) | ||||
| CHU de Toulouse Hôpital Larrey - Toulouse 2972315 - France | Contact (sur clinicalTrials) | ||||
| CHU St Etienne - Saint-Etienne 2980291 - France | Contact (sur clinicalTrials) | ||||
| CHU Sud de la Réunion - La Réunion 6619528 - France | Shakeel SUMODHEE, MD | Contact (sur clinicalTrials) | |||
| Clinique Saint-Hilaire - Rouen 2982652 - France | Contact (sur clinicalTrials) | ||||
| Hôpital Privé Arnault Tzanck - Mougins 2991551 - France | Contact (sur clinicalTrials) | ||||
| Hôpital Privé Arras Les Bonnettes - Arras 3036784 - France | Alexandre HENNI, MD | Contact (sur clinicalTrials) | |||
| Hôpital Privé Drôme Ardèche - Valence 2971053 - France | Mathieu BOSSET, MD | Contact (sur clinicalTrials) | |||
| Institut Claudius Regaud - Toulouse 2972315 - France | Jonathan KHALIFA, M.D | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie de l'Ouest - Site Paul Papin - Angers 3037656 - France | Amaury PAUMIER, MD | Contact (sur clinicalTrials) | |||
| Institut Sainte Catherine - Avignon 3035681 - France | Nicolas POUREL, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre André DUTREIX - Dunkirk 3020686 - France | Fatima MENIAI | Contact (sur clinicalTrials) | |||
| Centre Antoine Lacassagne - Nice 2990440 - France | Jérôme DOYEN, MD | Contact (sur clinicalTrials) | |||
| Centre Azuréen De Cancérologie - Mougins 2991551 - France | Contact (sur clinicalTrials) | ||||
| Centre Catalan d'Oncologie - Perpignan 2987914 - France | Sabine VIEILLOT, MD | Contact (sur clinicalTrials) | |||
| Centre François Baclesse - Caen 3029241 - France | Radj GERVAIS, MD | Contact (sur clinicalTrials) | |||
| Centre Georges Francois Leclerc - Dijon 3021372 - France | Aurélie LAGRANGE, MD | Contact (sur clinicalTrials) | |||
| Centre Henri Becquerel - Rouen 2982652 - France | Contact (sur clinicalTrials) | ||||
| Centre hospitalier de Cannes Simone Veil - Cannes 3028808 - France | Yannick DUVAL, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier de Dunkerque - Dunkirk 3020686 - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier de Montelimar - Montélimar 2992703 - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Dr Jean-Eric TECHER - Calais 3029162 - France | Fatima MENIAI, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire De Caen - Hôpital Cote De Nacre - Caen 3029241 - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier William Morey - Chalon-sur-Saône 3027484 - France | Contact (sur clinicalTrials) | ||||
| Centre Joliot Curie - Saint-Martin-Boulogne 2978439 - France | Anne-Catherine COURTECUISSE-DEGRENDEL, MD | Contact (sur clinicalTrials) | |||
| Centre Oscar Lambret - Lille 2998324 - France | Florence LE TINIER, MD | Contact (sur clinicalTrials) | |||
| CHRU de Brest - Brest 3030300 - France | Vincent BOURBONNE, MD | Contact (sur clinicalTrials) | |||
| CHU de Nîmes - Nîmes 2990363 - France | Sylvie VAN HULST, MD | Contact (sur clinicalTrials) | |||
| Clinique Ambroise Pare - Beuvry 3032903 - France | Jean-Briac PREVOST, MD | Contact (sur clinicalTrials) | |||
| Clinique Chenieux - 87039 - Limoges 2998286 - France | Xavier ZASADNY, MD | Contact (sur clinicalTrials) | |||
| Gustave Roussy - Villejuif 2968705 - France | Antonin LEVY, MD, PhD | Contact (sur clinicalTrials) | |||
| Hopital Charles Nicolle - Rouen 2982652 - France | Contact (sur clinicalTrials) | ||||
| Hôpital Européen Marseille - Marseille 2995469 - France | Jacques LE TREUT, MD | Contact (sur clinicalTrials) | |||
| Hôpital Privé Clairval - Marseille 2995469 - France | Contact (sur clinicalTrials) | ||||
| Hôpital Simone Veil Blois - Blois 3032213 - France | Contact (sur clinicalTrials) | ||||
| Institut Bergonie - Bordeaux 3031582 - France | Sophie COUSIN, MD | Contact (sur clinicalTrials) | |||
| Institut Curie - Hôpital René Huguenin - Saint-Cloud 2981041 - France | Joelle OTZ, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie de Bourgogne - Chalon-sur-Saône 3027484 - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancérologie de Bourgogne - Dijon 3021372 - France | Contact (sur clinicalTrials) | ||||
| Institut De Cancerologie De Lorraine - Vandœuvre-lès-Nancy 2970797 - France | Contact (sur clinicalTrials) | ||||
| Institut Jean Godinot - Reims 2984114 - France | Contact (sur clinicalTrials) | ||||
| Pôle départemental de Cancérologie Libérale 37 - Chambray-lès-Tours 3027343 - France | Thomas BOISSERIE, MD | Contact (sur clinicalTrials) | |||
| Polyclinique de l'Ormeau - Tarbes 2973385 - France | Contact (sur clinicalTrials) | ||||
| Polyclinique du Parc Drevon - Dijon 3021372 - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
INCLUSION CRITERIA:
1. Patient must have signed a written informed consent form prior to any study specific
procedures
2. Histologically or cytologically confirmed advanced (stage IIIB/IIIC/IV), squamous or
non-squamous NSCLC
3. NSCLC patients eligible for treatment with pembrolizumab and chemotherapy according
to the European Marketing Authorization:
1. squamous: in combination with carboplatin and either paclitaxel or
nab-paclitaxel
2. non squamous with no EGFR or ALK positive mutations: in combination with
pemetrexed and a platinum based chemotherapy
4. Patient ≥18 of age
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
6. Life expectancy >3 months
7. Measurable lesion as assessed by RECIST version 1.1
8. Metastases and/or primary tumour 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)
9. Patients must have adequate organ function defined by the following laboratory
results obtained within 14 days prior to the first study treatment:
1. absolute neutrophil count of ≥1 500 /mm³
2. platelets ≥ 100 000/mm³
3. haemoglobin >9 g/dL (transfusions allowed)
4. creatinine clearance >60 mL/min
5. bilirubin ≤1.5 X upper limit of normal (ULN) (unless Gilbert's syndrome where 3
X ULN is permitted)
6. serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5
X ULN (unless documented liver metastasis where ≤5 X ULN is permitted)
7. Alkaline phosphatase (ALP) ≤2.5 X ULN (unless documented bone or liver
metastasis where ≤5 X ULN is permitted)
8. International normalized ratio (INR), prothrombin (PT), and prothrombin time
(PTT) ≤1.5 X ULN (unless the subject is receiving anticoagulant therapy)
10. 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
11. Patients affiliated to the social security system (or equivalent)
12. 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
NON-INCLUSION CRITERIA:
1. Non-squamous NSCLC with targetable tumor mutations, activating EGFR mutations or ALK
translocation Note: documentation of these mutation for non-squamous histology is
mandatory as standard of care
2. Stage IIIB/IIIC NSCLC patient eligible to curative (thoracic radiotherapy or
surgery) treatments in first line treatment
3. Prior therapy with T-cell costimulation or checkpoint-targeted agents Note: Stage
I-III NSCLC who previously received single-agent anti-PD(L)1 immunotherapy and
ultimately develop metastases remain eligible (minimal immunotherapy washout period
of 3 months)
4. Clinical need of radiotherapy (e.g.: whole brain irradiation, painful metastasis,
bleeding, compressive metastases)
5. Irradiation within 2 months before inclusion
6. Leptomeningeal carcinomatosis, or metastases with indistinct borders making
targeting not feasible
7. Patient with evidence of active (presence of symptoms or requiring steroid
treatment) central nervous system (CNS) metastases and/or carcinomatous meningitis.
Patient with brain metastasis can be included if asymptomatic and not requiring
steroids
8. Metastases located within 3 cm of the previously irradiated structures (EQD2doses):
1. Spinal cord previously irradiated to >40 Gy;
2. Brachial plexus previously irradiated to >50 Gy;
3. Small intestine, large intestine, or stomach previously irradiated to >45 Gy;
4. Brainstem previously irradiated to >50 Gy;
5. Lung previously irradiated with prior V20Gy >30%
9. Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized
with hormonal substitution, psoriasis
10. Symptomatic interstitial lung disease
11. Systemic immunosuppression or systemic immunosuppressive medicinal products within 2
weeks prior to study entry
12. Concomitant treatment with steroids > 10 mg Note1: higher dose of steroids can be
prescribed in case of occurrence of toxicities during radiotherapy; prophylactic
dose of maximum 1 mg per kg during 2 weeks are authorized during the delivery of
more than 6 Gy per fraction Note2: temporary use of steroid (less than 4 weeks) at a
dose of 1 mg/kg is accepted
13. 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)
14. Known Acquired Immune Deficiency Syndrome (AIDS) or severe uncontrolled co-morbidity
15. Known currently active infection including hepatitis B and hepatitis C
16. Patient who was administered a live, attenuated vaccine within 28 days prior to
enrolment
17. Patient with any other disease or illness that 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
18. Patient who have taken any investigational medicinal product or have used an
investigational device within 30 days of inclusion
19. Pregnant or breast feeding woman
20. Person deprived of their liberty or under protective custody or guardianship
21. If pemetrexed: patient is unable or unwilling to take folic acid or vitamin B12
supplementation
22. Pre-existing peripheral neuropathy of a severity of grade ≥ 2 by NCI CTCAE v5.0
23. Known hypersensitivity to one of the compounds or substances used in this protocol
24. Major surgery within the 28 days before initiating study treatment
1. Patient must have signed a written informed consent form prior to any study specific
procedures
2. Histologically or cytologically confirmed advanced (stage IIIB/IIIC/IV), squamous or
non-squamous NSCLC
3. NSCLC patients eligible for treatment with pembrolizumab and chemotherapy according
to the European Marketing Authorization:
1. squamous: in combination with carboplatin and either paclitaxel or
nab-paclitaxel
2. non squamous with no EGFR or ALK positive mutations: in combination with
pemetrexed and a platinum based chemotherapy
4. Patient ≥18 of age
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
6. Life expectancy >3 months
7. Measurable lesion as assessed by RECIST version 1.1
8. Metastases and/or primary tumour 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)
9. Patients must have adequate organ function defined by the following laboratory
results obtained within 14 days prior to the first study treatment:
1. absolute neutrophil count of ≥1 500 /mm³
2. platelets ≥ 100 000/mm³
3. haemoglobin >9 g/dL (transfusions allowed)
4. creatinine clearance >60 mL/min
5. bilirubin ≤1.5 X upper limit of normal (ULN) (unless Gilbert's syndrome where 3
X ULN is permitted)
6. serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5
X ULN (unless documented liver metastasis where ≤5 X ULN is permitted)
7. Alkaline phosphatase (ALP) ≤2.5 X ULN (unless documented bone or liver
metastasis where ≤5 X ULN is permitted)
8. International normalized ratio (INR), prothrombin (PT), and prothrombin time
(PTT) ≤1.5 X ULN (unless the subject is receiving anticoagulant therapy)
10. 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
11. Patients affiliated to the social security system (or equivalent)
12. 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
NON-INCLUSION CRITERIA:
1. Non-squamous NSCLC with targetable tumor mutations, activating EGFR mutations or ALK
translocation Note: documentation of these mutation for non-squamous histology is
mandatory as standard of care
2. Stage IIIB/IIIC NSCLC patient eligible to curative (thoracic radiotherapy or
surgery) treatments in first line treatment
3. Prior therapy with T-cell costimulation or checkpoint-targeted agents Note: Stage
I-III NSCLC who previously received single-agent anti-PD(L)1 immunotherapy and
ultimately develop metastases remain eligible (minimal immunotherapy washout period
of 3 months)
4. Clinical need of radiotherapy (e.g.: whole brain irradiation, painful metastasis,
bleeding, compressive metastases)
5. Irradiation within 2 months before inclusion
6. Leptomeningeal carcinomatosis, or metastases with indistinct borders making
targeting not feasible
7. Patient with evidence of active (presence of symptoms or requiring steroid
treatment) central nervous system (CNS) metastases and/or carcinomatous meningitis.
Patient with brain metastasis can be included if asymptomatic and not requiring
steroids
8. Metastases located within 3 cm of the previously irradiated structures (EQD2doses):
1. Spinal cord previously irradiated to >40 Gy;
2. Brachial plexus previously irradiated to >50 Gy;
3. Small intestine, large intestine, or stomach previously irradiated to >45 Gy;
4. Brainstem previously irradiated to >50 Gy;
5. Lung previously irradiated with prior V20Gy >30%
9. Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized
with hormonal substitution, psoriasis
10. Symptomatic interstitial lung disease
11. Systemic immunosuppression or systemic immunosuppressive medicinal products within 2
weeks prior to study entry
12. Concomitant treatment with steroids > 10 mg Note1: higher dose of steroids can be
prescribed in case of occurrence of toxicities during radiotherapy; prophylactic
dose of maximum 1 mg per kg during 2 weeks are authorized during the delivery of
more than 6 Gy per fraction Note2: temporary use of steroid (less than 4 weeks) at a
dose of 1 mg/kg is accepted
13. 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)
14. Known Acquired Immune Deficiency Syndrome (AIDS) or severe uncontrolled co-morbidity
15. Known currently active infection including hepatitis B and hepatitis C
16. Patient who was administered a live, attenuated vaccine within 28 days prior to
enrolment
17. Patient with any other disease or illness that 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
18. Patient who have taken any investigational medicinal product or have used an
investigational device within 30 days of inclusion
19. Pregnant or breast feeding woman
20. Person deprived of their liberty or under protective custody or guardianship
21. If pemetrexed: patient is unable or unwilling to take folic acid or vitamin B12
supplementation
22. Pre-existing peripheral neuropathy of a severity of grade ≥ 2 by NCI CTCAE v5.0
23. Known hypersensitivity to one of the compounds or substances used in this protocol
24. Major surgery within the 28 days before initiating study treatment