Durvalumab for Small cell lung cancer

Inclusion criteria

• {"criterion_text":"- 1.\tFemale or male patients aged ≥18 years at the time of signing the Informed Consent Form (ICF)."}
• {"criterion_text":"- 10.\tBody weight >30 kg."}
• {"criterion_text":"- 2.\tWritten informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures. Additionally, signed and dated written genetic and/or biomarker informed consents, respectively, to collect baseline tissue and blood samples for future translational biomarker assessment at baseline, at the initiation of durvalumab maintenance treatment (cycles 1, 2, 3, 4, 7, 10, 13, 19, 26), and at end of treatment/progression."}
• {"criterion_text":"- 3.\tPatients must have histologically or cytologically documented limited stage SCLC (stage I-III SCLC [T any, N any, M0] according to the AJCC Cancer Staging Manual, [8th Edition] or the IASLC Staging Manual in Thoracic Oncology [2016]), i.e., patients whose disease can be encompassed within a radical radiation portal. Patients who are stage I or II must be medically inoperable as determined by investigator."}
• {"criterion_text":"- 4.\tWHO/ECOG PS of 0, 1 or 2 at enrolment, after CRT. A maximum of 20% of patients with ECOG 2 is allowed."}
• {"criterion_text":"- 5.\tReceived an appropriate first-line concurrent or sequential chemoradiotherapy regimen as defined below, unless after consultation with the study medical team an alternative is acceptable: o\tReceived 3-4 cycles of platinum-based chemotherapy concurrent or sequential with radiotherapy, which must be completed within 1 to 90 days prior to the first dose of durvalumab. o\tThe chemotherapy regimen must contain platinum and IV etoposide, administered as per local SoC regimens."}
• {"criterion_text":"- 6.\tReceived a total dose of radiation of 60 to 66 Gy (±10%) over approximately 6 weeks for standard QD radiation schedules or 45 Gy (±10%) over approximately 3 weeks for hyperfractionated BID radiation schedules."}
• {"criterion_text":"- 7.\tPatients must have achieved CR, PR, or SD and not have progressed following definitive, platinum-based chemoradiotherapy."}
• {"criterion_text":"- 8.\tAdequate organ and marrow function (independent of transfusion, infusion, or growth factor support for at least 14 days prior to obtaining screening labs), defined as below: o\tHaemoglobin ≥9.0 g/dL o\tAbsolute neutrophil count ≥1.5 x 109/L o\tPlatelet count ≥100 x 109/L o\tSerum bilirubin ≤1.5 x the ULN. This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia [predominantly unconjugated bilirubin] in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with their physician. o\tALT and AST ≤2.5 x ULN o\tMeasured creatinine clearance (CL) >40 mL/min or calculated CL >40 mL/min as determined by Cockcroft-Gault (using actual body weight)"}
• {"criterion_text":"- 9.\tMust have a life expectancy of at least 12 weeks."}

Exclusion criteria

• {"criterion_text":"- 1.\tMixed SCLC and NSCLC histology."}
• {"criterion_text":"- 10.\tActive infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive HBsAg result), hepatitis C (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies)."}
• {"criterion_text":"- 11.\tAny unresolved toxicity NCI Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 from previous CRT except for alopecia, vitiligo, and the laboratory values defined in the inclusion criteria: o\tPatients with grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician. o\tPatients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study physician."}
• {"criterion_text":"- 12.\tBrain metastases or spinal cord compression. All patients will have an MRI (preferred) or CT, preferably with IV contrast of the brain, prior to study entry, after CRT."}
• {"criterion_text":"- 13.\tMean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)."}
• {"criterion_text":"- 14.\tKnown allergy or hypersensitivity to any of the study drugs or any of the study drug excipients."}
• {"criterion_text":"- 15.\tPatients whose conditions have progressed while on CRT."}
• {"criterion_text":"- 16.\tMajor surgical procedure (as defined by the Investigator) within 42 days prior to the first dose of IP."}
• {"criterion_text":"- 17.\tCurrent or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: o\tIntranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection). o\tSystemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. o\tSteroids as premedication for hypersensitivity reactions (eg, CT scan premedication)."}
• {"criterion_text":"- 18.\tParticipation in another clinical study with an investigational product administered in the last 4 weeks."}
• {"criterion_text":"- 19.\tConcurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study."}
• {"criterion_text":"- 2.\tExtensive-stage SCLC."}
• {"criterion_text":"- 20.\tInvolvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)."}
• {"criterion_text":"- 21.\tFemale patients who are pregnant or breastfeeding and male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 3 months after the last dose of durvalumab."}
• {"criterion_text":"- 22.\tJudgment by the investigator that the patient should not participate in the study because the patient is unlikely to comply with study procedures, restrictions, and requirements."}
• {"criterion_text":"- 3.\tAny history of grade ≥2 pneumonitis."}
• {"criterion_text":"- 4.\tHistory of allogeneic organ transplantation."}
• {"criterion_text":"- 5.\tActive or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn’s disease], diverticulitis [except for 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: o\tPatients with vitiligo or alopecia. o\tPatients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. o\tAny chronic skin condition that does not require systemic therapy. o\tPatients without active disease in the last 5 years may be included but only after consultation with the study physician. o\tPatients with celiac disease controlled by diet alone."}
• {"criterion_text":"- 6.\tUncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent."}
• {"criterion_text":"- 7.\tHistory of another primary malignancy except for: o\tMalignancy 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. o\tAdequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. o\tAdequately treated carcinoma in situ without evidence of disease."}
• {"criterion_text":"- 8.\tHistory of leptomeningeal carcinomatosis."}
• {"criterion_text":"- 9.\tHistory of active primary immunodeficiency."}

Primary endpoints

• {"endpoint_text":"- •\tIncidence of grade ≥ 3 AEs","definition_or_measurement_approach":""}
• {"endpoint_text":"- •\tIncidence of imAE, defined as an AE that is associated with drug exposure and is consistent with an immune-mediated mechanism of action and there is no clear alternate etiology.","definition_or_measurement_approach":"An imAE is defined as an adverse event associated with drug exposure consistent with an immune-mediated mechanism with no clear alternate etiology."}
• {"endpoint_text":"- •\tIncidence of AEs that lead to treatment delays/interruptions or permanent discontinuation.","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- •\tProgression-Free Survival (PFS). Progression-Free Survival defined as the time from the date of first dose of durvalumab until the date of objective disease progression according RECIST 1.1 criteria assessed by investigator, or death (by any cause in the absence of progression). The measure of interest is the median PFS.","definition_or_measurement_approach":"PFS defined as time from first dose to objective disease progression per RECIST 1.1 by investigator, or death; measure of interest: median PFS."}
• {"endpoint_text":"- •\tOverall Survival (OS) rate at 36 months, defined as the percentage of patients that are still alive at 36 months.","definition_or_measurement_approach":"OS rate at 36 months = percentage of patients alive at 36 months after first dose."}
• {"endpoint_text":"- •\tAll AEs.","definition_or_measurement_approach":""}
• {"endpoint_text":"- •\tSerious AEs.","definition_or_measurement_approach":""}
• {"endpoint_text":"- •\t Factors to be analysed: -\tGender -\tAge range (<65 vs ≥65 years) -\tSmoking status -\tWHO/ECOG -\tPD-L1 status -\tDisease stage -\tCarboplatin vs cisplatin -\tType of radiotherapy: standard vs hyperfractionated -\tcCRT vs sCRT -\tResponse to CRT -\tTime to durvalumab initiation from last CRT dose -\tPCI","definition_or_measurement_approach":"Factors listed will be analysed as subgroup/factor analyses (e.g., age <65 vs ≥65, PD-L1 status)."}
• {"endpoint_text":"- •\tScores on the EORTC (European Organisation for Research and Treatment of Cancer) Core Quality of Life Questionnaire (EORTC QLQ-C30) and its specific module for lung cancer QLQ-LC29. Change from baseline in EORTC QLQ-C30 and EORTC QLQ-LC29 and time to deterioration in EORTC QLQ-C30.","definition_or_measurement_approach":"Change from baseline and time-to-deterioration in EORTC QLQ-C30 and QLQ-LC29 scores."}
• {"endpoint_text":"- •\tBiomarker analysis of tumour tissue sample at baseline to assess exploratory markers, which may include but is not limited to PD-L expressions. Biomarker analysis of blood samples at baseline, during treatment and at the end of treatment/progression, which may include but are not limited to ctDNA.","definition_or_measurement_approach":"Exploratory biomarker analyses on tumour tissue and blood (including PD-L1 expression, ctDNA) at baseline, during treatment and at end of treatment/progression."}

Spain

Earliest CTIS Part Ii Submission Date

16-06-2025

Latest Decision Or Authorization Date

22-10-2025

Processing Time Days

128

Number Of Sites

15

Number Of Participants

70

Primary sponsor

Full Name

Astrazeneca Farmaceutica Spain S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Apices Soluciones S.L.","duties_or_roles":"codes: 1,11,12,5,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Logista Pharma S.A.","duties_or_roles":"Manufacturing and Import","organisation_type":"Pharmaceutical company"}