Durvalumab After Chemoradiotherapy in Limited Stage Small Cell Lung Cancer.

NCT06992609 | Recruiting Phase 3

• 2 other identifiers: D419QL000092025-521340-37-00
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 15

Brief Summary

Lung cancer is a highly prevalent disease worldwide in women and men. In 2022, lung cancer stood as the most frequently diagnosed cancer with approximately 2.48 million new cases on a global scale, followed by cancers of the female breast (11.6%), colorectum (9.6%), prostate (7.3%), and stomach (4.9%). Lung cancer is the leading cause of cancer death worldwide according to data provided by the International Agency for Research on Cancer. In 2022 they estimated a 1.8 million deaths across the world. Specifically in Spain, from 1980 to 2022, lung cancer led to 745,182 deaths. Histologically, lung cancer (LC) can be classified into two major subtypes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), accounting for 85% and 15% of LC patients, respectively. Smoking is the major risk factor for SCLC. There are two stages of SCLC: limited-stage SCLC (LS-SCLC) and extensive-stage SCLC (ES-SCLC). Limited-stage (LS) means that the cancer is located on the ipsilateral hemithorax that can be encompassed within a radiation port while extensive-stage (ES) means that the cancer has spread widely throughout the lungs, to non-regional lymph nodes or to other organs. At present, LS is identified in \~30% of patients, and ES is identified in \~70% of patients with SCLC. With a 5-year survival rate of less than 7%, SCLC is still one of the most lethal malignancies and it is also characterized by early metastatic spread. Reflecting this high metastatic capacity, two thirds of patients already have tumor cell dissemination outside the chest at the time of initial diagnosis (ES-SCLC). Therefore, the number of patients with LS-SCLC who can benefit from multimodality therapy with potentially curative intent is limited. SCLC is a highly aggressive form of LC that typically recurs and progresses rapidly despite initial response to chemotherapy and radiotherapy in patients with LS-SCLC. The etoposide/platinum (EP) combination was the standard of care (SoC) for patients with ES-SCLC until 2019, when the addition of immunotherapy to EP chemotherapy was shown to improve survival, with up to 17% of patients remaining alive at 3 years. On the other hand, the SoC for patients with LS-SCLC is concurrent platinum-based chemoradiotherapy (cCRT) ± prophylactic cranial irradiation (PCI) that remained unchanged for decades. Several studies have shown that concurrent chemoradiotherapy (cCRT) is more effective than sequential CRT (sCRT) in LS-SCLC. Nonetheless, subject to the lymph node regions involvement and treatment-related toxicities, some patients do not undergo concurrent CRT and instead receive sequential CRT. In a non-interventional, retrospective cohort study of limited-stage SCLC patients conducted in France, Italy and the UK, sequential chemoradiotherapy accounts for 37.6% of all treatment patterns while concurrent chemoradiotherapy accounts for 35.1% of the whole therapies used as first line. ADRIATIC (NCT03703297) is a phase 3, randomized, double-blind, placebo-controlled, multicenter, global study evaluating durvalumab ± tremelimumab as consolidation therapy for patients with LS-SCLC who have not progressed after cCRT. Positive high-level results of the ADRIATIC clinical trial showed durvalumab demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) in patients with LS-SCLC who had not progressed following cCRT compared to placebo. Durvalumab was well tolerated, and AEs were consistent with the known safety profile. These data support the consolidation of durvalumab as a new SoC for patients with LS-SCLC who have not progressed after cCRT. There is limited information on the effectiveness and safety of durvalumab in a broader patient population with LS-SCLC, including those who received sequential CRT. Therefore, there remains an unmet need for additional data to help support and inform the healthcare decisions on the use of durvalumab as consolidation treatment for patients with LS-SCLC in real-world clinical practice. In addition, ADRIATIC study did not allow to include patients with ECOG PS 2 assessed after CRT. The present phase IIIb study will assess the safety and effectiveness of durvalumab in real world like LS-SCLC population. Furthermore, this trial will focus on patient characteristics, treatment exposure, administration, quality of life (QoL), effectiveness and safety providing insights into durvalumab use.

Conditions

Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (1)

• To describe the safety profile of durvalumab for patients with LS-SCLC who have not progressed following CRT.

  * Incidence of grade ≥ 3 AEs * Incidence 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. * Incidence of AEs that lead to treatment delays/interruptions or permanent discontinuation.

  90 days after last dose of durvalumab of the last patient.

Secondary Outcomes (3)

• To describe effectiveness of durvalumab for patients with LS-SCLC who have not progressed following CRT.

  From the date of first dose of durvalumab until the date of disease progression, death, withdrawn from study, or end of study (approximately 56 months)

• To describe effectiveness of durvalumab for patients with LS-SCLC who have not progressed following CRT.

  Up to 36 months

• To further describe safety profile of durvalumab for patients with LS-SCLC who have not progressed following CRT.

  90 days after last dose of durvalumab of the last patient.

Study Arms (1)

Durvalumab

EXPERIMENTAL

Durvalumab after completion of CRT

Drug: Durvalumab

Interventions

Durvalumab DRUG

Durvalumab (IV) every 4 weeks until a maximum of 24 months.

Also known as: Consolidation treatment

Durvalumab

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male patients aged ≥18 years at the time of signing the Informed Consent Form (ICF).
• Written 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.
• Patients 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.
• WHO/ECOG PS of 0, 1 or 2 at enrolment, after CRT. A maximum of 20% of patients with ECOG 2 is allowed.
• Received an appropriate first-line concurrent or sequential chemoradiotherapy regimen as defined below, unless after consultation with the study medical team an alternative is acceptable:
• Received 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.
• The chemotherapy regimen must contain platinum and IV etoposide, administered as per local SoC regimens.
• Received 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.
• Patients must have achieved CR, PR, or SD and not have progressed following definitive, platinum-based chemoradiotherapy. NOTE: PCI may be delivered at the discretion of investigator and local standard of care and must be conducted after the end of CRT and completed between 1 to 90 days to first dose of IP.
• Adequate 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:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count ≥1.5 x 109/L
• Platelet count ≥100 x 109/L
• Serum 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.
• ALT and AST ≤2.5 x ULN

You may not qualify if:

• Mixed SCLC and NSCLC histology.
• Extensive-stage SCLC.
• Any history of grade ≥2 pneumonitis.
• History of allogeneic organ transplantation.
• Active 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:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
• Any chronic skin condition that does not require systemic therapy.
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
• Patients with celiac disease controlled by diet alone.
• Uncontrolled 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.
• History of another primary malignancy except for:
• 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.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (15)

Research Site

A Coruña, 15006, Spain

RECRUITING

Research Site

Badajoz, 06080, Spain

RECRUITING

Research Site

Barakaldo, 48903, Spain

RECRUITING

Research Site

Barcelona, 08035, Spain

RECRUITING

Research Site

Barcelona, 08036, Spain

RECRUITING

Research Site

Barcelona, 08907, Spain

RECRUITING

Research Site

Jerez de la Frontera, 11407, Spain

RECRUITING

Research Site

Madrid, 28041, Spain

RECRUITING

Research Site

Madrid, 28046, Spain

RECRUITING

Research Site

Málaga, 29010, Spain

RECRUITING

Research Site

Oviedo, 33011, Spain

RECRUITING

Research Site

Santander, 39008, Spain

RECRUITING

Research Site

Seville, 41013, Spain

RECRUITING

Research Site

Valencia, 46026, Spain

RECRUITING

Research Site

Zaragoza, 50009, Spain

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2025
• First Posted: May 28, 2025
• Study Start: September 15, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

ES (15)