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Durvalumab (immunotherapy) maintenance after thoracic chemoradiotherapy (CRT) in frail small cell lung cancer patients whose disease is limited to the thorax

Phase 2
Recruiting
Conditions
Histologically confirmed frail Limited Disease Small Cell Lung Cancer (ECOG PS 2, ECOG PS 0-1 and older than 70 or did not receive a concomitant thoracic CRT because of comorbidities) previously untreated
Registration Number
2024-512224-11-00
Lead Sponsor
Unicancer
Brief Summary

To evaluate the activity in term of the progression free survival (PFS) (according to RECIST v 1.1 per investigator) patients on durvalumab maintenance treatment following thoracic CRT in LD-SCLC patients

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruiting
Sex
Not specified
Target Recruitment
29
Inclusion Criteria

For Screening_Patient must have signed a first written informed consent form prior to screening visit and to any trial specific procedures

For Screening_Patients ≥18 years old.

For Inclusion_Patient must have signed a second written informed consent form prior to inclusion and to any specific trial procedure

For Inclusion_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)._

For Inclusion_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. All other schedules/methods performed need to be centrally approved before the inclusion.

For Inclusion_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

For Inclusion_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_

For Inclusion_HRQoL questionnaire performed

For Inclusion_Adequate haematological function  Haemoglobin >9 g/dL.  Platelet count >100 x 109L.  Neutrophil count >1.5 x 109L.

For Screening_Body weight >30 kg.

For inclusion_Adequate renal function with a creatinine clearance ≥40 ml/min calculated with the Cockcroft-Gault formula._

For Screening_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

For Inclusion_Adequate hepatic function:  Total bilirubin <1.5 Upper limit of normal (ULN).  AST and ALT <2.5 ULN.  Alkaline phosphatase <2.5 ULN.

For Inclusion_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

For Screening_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 orwith carboplatin AUC5 to AUC6 etoposide regimen

For Screening_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

For Inclusion_Body weight >30 kg

For Screening_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

For Screening_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.

For Screening_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

For Screening_Patients affiliated to the social security system

For Screening_Histological confirmation of SCLC

For Screening_Measurable disease according to RECIST v1.1 criteria

For Screening_Patients must not have been previously treated for the SCLC. Note: patients who have already begun the initial CRT are eligible

Exclusion Criteria

History of another primary malignancy except for a. 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. b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. c. Adequately treated carcinoma in situ without evidence of disease.

Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection). b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. c. Steroids as premedication for hypersensitivity reactions (e.g., CT-scan premedication).

Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab. Note: Included patients should not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab.

Patients with known or suspected hypersensitivity to durvalumab or any of its excipients

Patients who participated in another therapeutic trial within the 30 days prior to the start of the trial (screening phase included).

Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.

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

Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Persons deprived of their liberty or under protective custody or guardianship

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.

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: a. Patients with vitiligo or alopecia b. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement c. Any chronic skin condition that does not require systemic therapy d. Patients without active disease in the last 5 years may be included but only after consultation with the study physician e. Patients with celiac disease controlled by diet alone.

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.

History of leptomeningeal carcinomatosis

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.

History of allogenic organ transplantation

History of active primary immunodeficiency

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.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
PFS is defined by investigator as the time from inclusion until disease progression (per RECIST v1.1) or death from any cause, whichever occurs first.

PFS is defined by investigator as the time from inclusion until disease progression (per RECIST v1.1) or death from any cause, whichever occurs first.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS) is defined as the time from inclusion to death due to any cause. Patients still alive at the time of analysis (including lost to follow-up) will be censored at the last known alive date.

Overall Survival (OS) is defined as the time from inclusion to death due to any cause. Patients still alive at the time of analysis (including lost to follow-up) will be censored at the last known alive date.

Safety profile: occurrence of adverse events coded using NCI CTC-AE version 5.0.

Safety profile: occurrence of adverse events coded using NCI CTC-AE version 5.0.

Quality of life (QL) will be assessed by the European Organization for Research and Treatment of Cancer (EORTC) core QL questionnaire, the EORTC QLQ-C30 and LC13 questionnaires (Lung Cancer Module).

Quality of life (QL) will be assessed by the European Organization for Research and Treatment of Cancer (EORTC) core QL questionnaire, the EORTC QLQ-C30 and LC13 questionnaires (Lung Cancer Module).

Trial Locations

Locations (33)

Polyclinique De Limoges

🇫🇷

Limoges Cedex I, France

Hospices Civils De Lyon

🇫🇷

Bron, France

Centre Francois Baclesse

🇫🇷

Caen Cedex 5, France

Les Hopitaux Nord-Ouest

🇫🇷

Villefranche Sur Saone Cedex, France

Centre Hospitalier De La Cote Basque

🇫🇷

Bayonne, France

Centre Leon Berard

🇫🇷

Lyon, France

Institut Curie

🇫🇷

Paris, France

Sainte Catherine Institut Du Cancer Avignon-Provence

🇫🇷

Avignon Cedex 9, France

Centre d'Oncologie Saint-Yves

🇫🇷

VANNES, France

Hopital Europeen Marseille

🇫🇷

Marseille, France

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Polyclinique De Limoges
🇫🇷Limoges Cedex I, France
Xavier ZASADNY
Site contact
+33555454800
xz@imagemed-87.com

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