Trial Title:
Durvalumab Maintenance After Thoracic Chemoradiotherapy in Frail Small Cell Lung Cancer Patients Whose Disease is Limited to the Thorax
NCT ID:
NCT05617963
Condition:
Small Cell Lung Carcinoma
Conditions: Official terms:
Small Cell Lung Carcinoma
Durvalumab
Conditions: Keywords:
immunotherapy
maintenance treatment
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Patients will be randomized (1:1) to either:
• Experimental arm (A): the patients will receive durvalumab intravenously 1500 mg every
4 weeks until disease progression, unacceptable toxicity, death, patient's decision, or
for a maximum of 24 months (26 doses/cycles).
Or
• Control arm (B) or surveillance arm
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Durvalumab
Description:
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 will receive durvalumab intravenously 1500 mg
every 4 weeks until disease progression, unacceptable toxicity, death or patient's
decision for a maximum of 24 months.
Arm group label:
Durvalumab treatment
Summary:
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.
Detailed description:
Small Cell Lung Cancer (SCLC) is a rare tumor, accounting nowadays for 10-15% of all new
lung cancer diagnosis. Approximately one third of patients present with limited disease
(LD-SCLC) confined to the chest with a median survival from 18 to 24 months and a 5-year
survival rate between 20% and 25%. A platinum-based chemotherapy combined with etoposide
and a concurrent thoracic radiotherapy represents the standard of care for LD-SCLC
treatment with a median PFS of 12 months. However, sequential radiotherapy may be
preferable for patients with poor performance status or having comorbidity predisposing
to a worst tolerability. Clinical evidence supports the immunogenicity of SCLC and the
involvement of immune activity in SCLC development and prognosis.
Several immune checkpoint inhibitors got the approbation in first and further lines for
the advanced SCLC in the last decade. The most important results have been achieved in
the first-line setting for patients receiving a combination of platinum - etoposide
chemotherapy and an anti-PD1/PDL-1 inhibitor compared to chemotherapy alone. However,
despite these were the first positive results after a while in this setting, the modest
absolute benefit showed (3 months) have to be taking into account. The possibility to
enhance the immunotherapy efficacy in SCLC field with the radiotherapy administered as
part of the standard treatment for a LD-SCLC seems to be a great opportunity. In the
PACIFIC trial, the sequential administration of durvalumab in patients with locally
advanced, unresectable, stage III Non-Small-Cell Lung Cancer (NSCLC) whose disease had
not progressed following platinum-based concurrent thoracic CRT showed a dramatic overall
survival improvement compared to placebo, with manageable toxicities. The ADRIATIC phase
III trial, is currently recruiting LD-SCLC patients not progressing after the concomitant
CRT (NCT03703297). Patients are randomized to receive durvalumab, durvalumab plus
tremelimumab or placebo as maintenance treatment. In this trial, only ECOG PS 0-1
patients able to receive a concomitant CRT are eligible. However, in our clinical
practice, LD-SCLC patients may not respect these criteria due to the aggressiveness of
cancer and comorbidities.
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.
Criteria for eligibility:
Criteria:
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.
Exclusion 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Centre de Radiothérapie du Pays d'Aix
Address:
City:
Aix-en-Provence
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Centre Hospitalier du Pays d'Aix
Address:
City:
Aix-en-Provence
Country:
France
Status:
Recruiting
Contact:
Last name:
Marie BERNARDI
Facility:
Name:
CHU d'Angers
Address:
City:
Angers
Country:
France
Status:
Recruiting
Contact:
Last name:
Thierry URBAN
Facility:
Name:
Institut de Cancérologie de l'Ouest - Site Paul Papin
Address:
City:
Angers
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Institut du Cancer Avignon-Provence
Address:
City:
Avignon
Country:
France
Status:
Recruiting
Contact:
Last name:
Nicolas POUREL
Facility:
Name:
Centre d'Oncologie du Pays Basque
Address:
City:
Bayonne
Country:
France
Status:
Active, not recruiting
Facility:
Name:
CH de la côte Basque
Address:
City:
Bayonne
Country:
France
Status:
Recruiting
Contact:
Last name:
Marielle SABATINI
Facility:
Name:
Clinique Belharra
Address:
City:
Bayonne
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Aurélien BLOUET
Facility:
Name:
Centre François Baclesse
Address:
City:
Caen
Country:
France
Status:
Recruiting
Contact:
Last name:
Pierre DEMONTROND
Facility:
Name:
CHU de CAEN
Address:
City:
Caen
Country:
France
Status:
Recruiting
Contact:
Last name:
Simon DESHAYES
Facility:
Name:
CH de Cholet
Address:
City:
Cholet
Country:
France
Status:
Recruiting
Contact:
Last name:
Philippe MASSON
Facility:
Name:
Centre Jean Perrin
Address:
City:
Clermont-Ferrand
Country:
France
Status:
Recruiting
Contact:
Last name:
Pascale DUBRAY LONGERAS
Facility:
Name:
CHI Créteil
Address:
City:
Créteil
Country:
France
Status:
Recruiting
Contact:
Last name:
Christos CHOUAID
Facility:
Name:
Centre George François Leclerc
Address:
City:
Dijon
Country:
France
Status:
Recruiting
Contact:
Last name:
Courèche KADERBHAI
Facility:
Name:
CHU Grenoble Alpes
Address:
City:
Grenoble
Country:
France
Status:
Recruiting
Contact:
Last name:
Denis MOROT-SIBILOT
Facility:
Name:
Centre Oscar Lambret
Address:
City:
Lille
Country:
France
Status:
Recruiting
Contact:
Last name:
Elisabeth GAYE
Facility:
Name:
CHU Dupuytren
Address:
City:
Limoges
Country:
France
Status:
Recruiting
Contact:
Last name:
Alain VERGNENEGRE
Facility:
Name:
Polyclinique de Limoges -Site Clinique Chénieux
Address:
City:
Limoges
Country:
France
Status:
Recruiting
Contact:
Last name:
Xavier ZASADNY
Facility:
Name:
Groupe Hospitalier Bretagne Sud
Address:
City:
Lorient
Country:
France
Status:
Recruiting
Contact:
Last name:
Delphine ARGO LEIGNEL
Facility:
Name:
Centre Léon Bérard
Address:
City:
Lyon
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Aurélie SWALDUZ
Facility:
Name:
APHM - Hôpital Nord
Address:
City:
Marseille
Country:
France
Status:
Recruiting
Contact:
Last name:
Laurent GREILLIER
Facility:
Name:
Hopital européen Marseille
Address:
City:
Marseille
Country:
France
Status:
Recruiting
Contact:
Last name:
Jacques LE TREUT
Facility:
Name:
Hopital privé Clairval
Address:
City:
Marseille
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Institut Paoli-Calmettes
Address:
City:
Marseille
Country:
France
Status:
Recruiting
Contact:
Last name:
Louis STOFFAES
Facility:
Name:
Institut régional du Cancer de Montpellier - ICM Val d'Aurelle
Address:
City:
Montpellier
Country:
France
Status:
Recruiting
Contact:
Last name:
Pierre BOISSELIER
Facility:
Name:
Centre Azuréen de Cancérologie
Address:
City:
Mougins
Country:
France
Status:
Recruiting
Contact:
Last name:
Alexander FALK
Facility:
Name:
Hôpital Privé Arnault Tzanck
Address:
City:
Mougins
Country:
France
Status:
Recruiting
Contact:
Last name:
Alexander FALK
Facility:
Name:
Hopital privé du Confluent
Address:
City:
Nantes
Country:
France
Status:
Recruiting
Contact:
Last name:
Claude EL KOURI
Facility:
Name:
Hôpital Tenon APHP
Address:
City:
Paris
Country:
France
Status:
Recruiting
Contact:
Last name:
Anthony CANELLAS
Facility:
Name:
Institut Curie
Address:
City:
Paris
Country:
France
Status:
Recruiting
Contact:
Last name:
Nicolas GIRARD
Contact backup:
Last name:
Elisa GOBBINI
Facility:
Name:
CARIO
Address:
City:
Plérin
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Institut Godinot
Address:
City:
Reims
Country:
France
Status:
Recruiting
Contact:
Last name:
Alain PREVOST
Facility:
Name:
Centre Henri Becquerel
Address:
City:
Rouen
Country:
France
Status:
Recruiting
Contact:
Last name:
Sébastien THUREAU
Facility:
Name:
CHU de ROUEN
Address:
City:
Rouen
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Florian GUISIER
Facility:
Name:
CH Saint Brieuc
Address:
City:
Saint-Brieuc
Country:
France
Status:
Recruiting
Contact:
Last name:
Gwenaelle LEGARFF
Facility:
Name:
Institut de Cancérologie de l'Ouest - Site René Gauducheau
Address:
City:
Saint-Herblain
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Sandrine HIRET
Facility:
Name:
Hopital Nord Ouest - Villefranche sur Saône
Address:
City:
Villefranche-sur-Saône
Country:
France
Status:
Recruiting
Contact:
Last name:
Lionel FALCHERO
Start date:
March 24, 2023
Completion date:
March 30, 2029
Lead sponsor:
Agency:
UNICANCER
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Source:
UNICANCER
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05617963
