Informations générales (source: ClinicalTrials.gov)
A Phase II Study of Durvalumab (MEDI 4736) Maintenance in Frail Limited Disease Small Cell Lung Cancer Patients After Thoracic Chemoradiotherapy (CRT) (DURVALUNG)
Interventional
Phase 2
UNICANCER (Voir sur ClinicalTrials)
mars 2023
mars 2029
29 juin 2024
This study is an academic-lead, open-label, multicenter, randomized phase II trial for
frail limited disease Small Cell Lung Cancer (LD-SCLC) patients.
Frail conditions are: Eastern Cooperative Oncology Group performance status (ECOG PS) 2
or ECOG PS 0-1 and older than 70 or ECOG PS 0-1 and did not receive a concomitant
thoracic chemo-radiotherapy (CRT) because of comorbidities.
During the screening phase, patients complete either the standard concomitant or
sequential thoracic CRT and cisplatin-etoposide regimen or carboplatin AUC5 to AUC6
etoposide regimen.
Patients showing a disease control (defined as stable disease [SD], partial response
[PR], or complete response [CR] according to RECIST v1.1) at the radiological evaluation
performed after the end of thoracic CRT can receive prophylactic cranial irradiation
(PCI) as per local practice. They will then be randomized to receive durvalumab every 4
weeks (experimental arm A) or surveillance (control arm B) as per standard of care.
Thus, DURVALUNG study aims to evaluate the efficacy of durvalumab maintenance treatment
in frail LD-SCLC patients who have not progressed following platinum-based concomitant or
sequential CRT.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CHI DE CRETEIL | Christos CHOUAID | 29/03/2024 01:30:03 | Contacter | ||
| CLCC INSTITUT CURIE | 04/12/2024 12:44:15 | 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 Tenon | Anthony CANELLAS | 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 | |||||
| APHM - Hôpital Nord - Marseille - France | Laurent GREILLIER | Contact (sur clinicalTrials) | |||
| CARIO - Plérin - France | Contact (sur clinicalTrials) | ||||
| Centre Azuréen de Cancérologie - Mougins - France | Alexander FALK | Contact (sur clinicalTrials) | |||
| Centre de Radiothérapie du Pays d'Aix - Aix-en-Provence - France | Contact (sur clinicalTrials) | ||||
| Centre d'Oncologie du Pays Basque - Bayonne - France | Contact (sur clinicalTrials) | ||||
| Centre François Baclesse - Caen - France | Pierre DEMONTROND | Contact (sur clinicalTrials) | |||
| Centre George François Leclerc - Dijon - France | Courèche KADERBHAI | Contact (sur clinicalTrials) | |||
| Centre Henri Becquerel - Rouen - France | Sébastien THUREAU | Contact (sur clinicalTrials) | |||
| Centre Hospitalier du Pays d'Aix - Aix-en-Provence - France | Marie BERNARDI | Contact (sur clinicalTrials) | |||
| Centre Jean Perrin - Clermont-Ferrand - France | Pascale DUBRAY LONGERAS | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - Lyon - France | Aurélie SWALDUZ | Contact (sur clinicalTrials) | |||
| Centre Oscar Lambret - Lille - France | Elisabeth GAYE | Contact (sur clinicalTrials) | |||
| CH de Cholet - Cholet - France | Philippe MASSON | Contact (sur clinicalTrials) | |||
| CH de la côte Basque - Bayonne - France | Marielle SABATINI | Contact (sur clinicalTrials) | |||
| CH Saint Brieuc - Saint-Brieuc - France | Gwenaelle LEGARFF | Contact (sur clinicalTrials) | |||
| CHI Créteil - Créteil - France | Christos CHOUAID | Contact (sur clinicalTrials) | |||
| CHU d'Angers - Angers - France | Thierry URBAN | Contact (sur clinicalTrials) | |||
| CHU de CAEN - Caen - France | Simon DESHAYES | Contact (sur clinicalTrials) | |||
| CHU de ROUEN - Rouen - France | Florian GUISIER | Contact (sur clinicalTrials) | |||
| CHU Dupuytren - Limoges - France | Alain VERGNENEGRE | Contact (sur clinicalTrials) | |||
| CHU Grenoble Alpes - Grenoble - France | Denis MOROT-SIBILOT | Contact (sur clinicalTrials) | |||
| Clinique Belharra - Bayonne - France | Aurélien BLOUET | Contact (sur clinicalTrials) | |||
| Groupe Hospitalier Bretagne Sud - Lorient - France | Delphine ARGO LEIGNEL | Contact (sur clinicalTrials) | |||
| Hopital européen Marseille - Marseille - France | Jacques LE TREUT | Contact (sur clinicalTrials) | |||
| Hopital Nord Ouest - Villefranche sur Saône - Villefranche-sur-Saône - France | Lionel FALCHERO | Contact (sur clinicalTrials) | |||
| Hôpital Privé Arnault Tzanck - Mougins - France | Alexander FALK | Contact (sur clinicalTrials) | |||
| Hopital privé Clairval - Marseille - France | Contact (sur clinicalTrials) | ||||
| Hopital privé du Confluent - Nantes - France | Claude EL KOURI | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie de l'Ouest - Site Paul Papin - Angers - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancérologie de l'Ouest - Site René Gauducheau - Saint-Herblain - France | Sandrine HIRET | Contact (sur clinicalTrials) | |||
| Institut du Cancer Avignon-Provence - Avignon - France | Nicolas POUREL | Contact (sur clinicalTrials) | |||
| Institut Godinot - Reims - France | Alain PREVOST | Contact (sur clinicalTrials) | |||
| Institut Paoli-Calmettes - Marseille - France | Louis STOFFAES | Contact (sur clinicalTrials) | |||
| Institut régional du Cancer de Montpellier - ICM Val d'Aurelle - Montpellier - France | Pierre BOISSELIER | Contact (sur clinicalTrials) | |||
| Polyclinique de Limoges -Site Clinique Chénieux - Limoges - France | Xavier ZASADNY | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
Criteria for Screening
1. Patient must have signed a first written informed consent form prior to screening
visit and to any trial specific procedures.
2. Histological confirmation of SCLC.
3. Limited disease (T0-T4, N0-N3 and M0) according to the TNM classification 8th
edition or to the VALSG 2-stage classification. As per standard guidelines a
complete radiological evaluation has to be performed within 28 days before the start
of induction chemotherapy including all the radiological exams below:
- Total body PET- scan.
- Contrast enhanced CT-scan of thorax and upper abdomen.
- Contrast enhanced MRI or CT-scan of brain.
4. Measurable disease according to RECIST v1.1 criteria.
5. Patients must not have been previously treated for the SCLC. Note: patients who have
already begun the initial CRT are eligible.
6. Patients ≥18 years old.
7. Body weight >30 kg.
8. Patients can be candidate to concomitant or sequential thoracic CRT by IMRT.
Patients have to receive at least 60 Gy (one-daily fraction of 1.8-2 Gy) or 45 Gy
twice daily (1.5 Gy per fraction) combined with cisplatin-etoposide regimen or with
carboplatin AUC5 to AUC6 etoposide regimen.
9. Patients that received previous thorax radiotherapy may be eligible if they can
receive the CRT schedule planned in the clinical study according to previous
irradiation fields and, in any case, after the medical monitor agreement.
10. Women of childbearing potential must have a negative serum beta-HCG test before the
beginning of the trial, during the study treatment and for a period of at least 3
months after the last administration of the experimental drug.
11. All sexually active men and women of childbearing potential must use an effective
contraception method for the duration of study treatment and for 3 months after
completing treatment.
12. Patients affiliated to the social security system.
13. Patient must be willing and able to comply with the protocol for the duration of the
trial including undergoing treatment and scheduled visits, and examinations
including follow-up.
Criteria for Randomization:
1. Patient must have signed a second written informed consent form prior to
randomization and to any specific trial procedure.
2. Patients must have completed concomitant or sequential thoracic CRT by IMRT:
Patients that received concomitant or sequential thoracic CRT must have received at
least 60 Gy (one-daily fraction of 1.8-2 Gy) or 45 Gy twice daily (1.5 Gy per
fraction) combined with cisplatin-etoposide regimen or with carboplatin AUC5 to AUC6
etoposide regimen.
3. Confirmation of disease control (SD, CR or PR) at radiological assessment with
contrast enhanced thorax and upper abdomen CT-scan or PET-CT and contrast enhanced
brain CT-scan or MRI after the thoracic CRT according to RECIST v1.1.
4. Use of brain MRI in case of PCI avoidance is mandatory. PCI has to be prescribed
according to the investigator's choice and the local recommendations.
5. Patients must belong to one of these groups at the screening visit after the
thoracic CRT :
- ECOG PS 2.
- ECOG PS 0-1 and older than 70.
- ECOG PS 0-1 and who did not receive a concomitant thoracic CRT because of
comorbidities (radiotherapy beginning before D1C3 of chemotherapy).
6. Adequate haematological function
- Haemoglobin >9 g/dL.
- Platelet count >100 x 10⁹L.
- Neutrophil count >1.5 x 10⁹L.
7. Adequate renal function with a creatinine clearance ≥40 ml/min calculated with the
Cockcroft-Gault formula.
8. Adequate hepatic function:
- Total bilirubin <1.5 Upper limit of normal (ULN).
- AST and ALT <2.5 ULN.
- Alkaline phosphatase <2.5 ULN.
9. HRQoL questionnaire performed.
10. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria.
Criteria for Screening
1. Patient must have signed a first written informed consent form prior to screening
visit and to any trial specific procedures.
2. Histological confirmation of SCLC.
3. Limited disease (T0-T4, N0-N3 and M0) according to the TNM classification 8th
edition or to the VALSG 2-stage classification. As per standard guidelines a
complete radiological evaluation has to be performed within 28 days before the start
of induction chemotherapy including all the radiological exams below:
- Total body PET- scan.
- Contrast enhanced CT-scan of thorax and upper abdomen.
- Contrast enhanced MRI or CT-scan of brain.
4. Measurable disease according to RECIST v1.1 criteria.
5. Patients must not have been previously treated for the SCLC. Note: patients who have
already begun the initial CRT are eligible.
6. Patients ≥18 years old.
7. Body weight >30 kg.
8. Patients can be candidate to concomitant or sequential thoracic CRT by IMRT.
Patients have to receive at least 60 Gy (one-daily fraction of 1.8-2 Gy) or 45 Gy
twice daily (1.5 Gy per fraction) combined with cisplatin-etoposide regimen or with
carboplatin AUC5 to AUC6 etoposide regimen.
9. Patients that received previous thorax radiotherapy may be eligible if they can
receive the CRT schedule planned in the clinical study according to previous
irradiation fields and, in any case, after the medical monitor agreement.
10. Women of childbearing potential must have a negative serum beta-HCG test before the
beginning of the trial, during the study treatment and for a period of at least 3
months after the last administration of the experimental drug.
11. All sexually active men and women of childbearing potential must use an effective
contraception method for the duration of study treatment and for 3 months after
completing treatment.
12. Patients affiliated to the social security system.
13. Patient must be willing and able to comply with the protocol for the duration of the
trial including undergoing treatment and scheduled visits, and examinations
including follow-up.
Criteria for Randomization:
1. Patient must have signed a second written informed consent form prior to
randomization and to any specific trial procedure.
2. Patients must have completed concomitant or sequential thoracic CRT by IMRT:
Patients that received concomitant or sequential thoracic CRT must have received at
least 60 Gy (one-daily fraction of 1.8-2 Gy) or 45 Gy twice daily (1.5 Gy per
fraction) combined with cisplatin-etoposide regimen or with carboplatin AUC5 to AUC6
etoposide regimen.
3. Confirmation of disease control (SD, CR or PR) at radiological assessment with
contrast enhanced thorax and upper abdomen CT-scan or PET-CT and contrast enhanced
brain CT-scan or MRI after the thoracic CRT according to RECIST v1.1.
4. Use of brain MRI in case of PCI avoidance is mandatory. PCI has to be prescribed
according to the investigator's choice and the local recommendations.
5. Patients must belong to one of these groups at the screening visit after the
thoracic CRT :
- ECOG PS 2.
- ECOG PS 0-1 and older than 70.
- ECOG PS 0-1 and who did not receive a concomitant thoracic CRT because of
comorbidities (radiotherapy beginning before D1C3 of chemotherapy).
6. Adequate haematological function
- Haemoglobin >9 g/dL.
- Platelet count >100 x 10⁹L.
- Neutrophil count >1.5 x 10⁹L.
7. Adequate renal function with a creatinine clearance ≥40 ml/min calculated with the
Cockcroft-Gault formula.
8. Adequate hepatic function:
- Total bilirubin <1.5 Upper limit of normal (ULN).
- AST and ALT <2.5 ULN.
- Alkaline phosphatase <2.5 ULN.
9. HRQoL questionnaire performed.
10. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria.
1. History of another primary malignancy except for
1. Malignancy treated with curative intent and with no known active disease ≥5
years before the first dose of durvalumab and of low potential risk for
recurrence.
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease.
3. Adequately treated carcinoma in situ without evidence of disease.
2. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness that
would limit compliance with study requirement, substantially increase risk of
incurring AEs or compromise the ability of the patient to give written informed
consent.
3. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to
this criterion:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
5. Patients with celiac disease controlled by diet alone.
4. Any concurrent chemotherapy, immune checkpoint inhibitors, biologic, or hormonal
therapy for cancer treatment. Concurrent use of hormonal therapy for
non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
5. History of leptomeningeal carcinomatosis.
6. Major surgical procedure (as defined by the Investigator) including surgical
resection of the primary disease, within 28 days prior to the first dose of IMP.
Note: Local surgery of isolated lesions for palliative intent is acceptable.
7. History of allogenic organ transplantation.
8. History of active primary immunodeficiency.
9. Known active infection including tuberculosis (clinical evaluation that includes
clinical history, physical examination and radiographic findings, or TB testing in
line with local practice) and hepatitis B and hepatitis C (positive hepatitis C
virus [HCV] antibody, hepatitis B virus [HBV] surface antigen [HBsAg] or HBV core
antibody [anti-HBc]).Patients with a past or resolved HBV infection (defined as the
presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.
Patients positive for HCV antibody are eligible only if polymerase chain reaction is
negative for HCV RNA. Patients known to have been tested positive for human
immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) are not eligible.
10. Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection).
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent.
3. Steroids as premedication for hypersensitivity reactions (e.g., CT-scan
premedication).
11. Receipt of live attenuated vaccine within 30 days prior to the first dose of
durvalumab.
Note: Patients randomized in experimental arm should not receive live vaccine whilst
receiving durvalumab and up to 30 days after the last dose of durvalumab.
12. Patients with known or suspected hypersensitivity to durvalumab or any of its
excipients.
13. Patients who participated in another therapeutic trial within the 30 days prior to
the start of the trial (screening phase included).
14. Prior randomisation or treatment in a previous durvalumab clinical study regardless
of treatment arm assignment.
15. Female patients who are pregnant or breast feeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy.
16. Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule.
17. Persons deprived of their liberty or under protective custody or guardianship.