Addition of Thoracic Consolidation Radiotherapy to the Maintenance Immunotherapy for ES-SCLC (STONE-001)

Official title

Addition of High-dose Hyperfractionated Simultaneous Integrated Boost Radiotherapy to the Maintenance Therapy with PD-L1 Inhibitor Versus PD-L1 Inhibitor Alone for Extensive Stage Small Cell Lung Cancer (STONE-001)

Overview

This study is expected to enroll 182 patients with partial response or stable disease after first-line immunochemotherapy for extensive-stage small cell lung cancer and eligible for thoracic consolidation radiotherapy within 2 years. Patients were randomized 2:1 to immune single-agent maintenance therapy in combination with hyperfractionated high-dose radiotherapy and immune single-agent maintenance therapy after being assessed by the investigator as otherwise eligible for enrollment. Patients in both arms received maintenance therapy with the PD-L1 inhibitor, atezolizumab or dulvedolizumab, until disease progression, unacceptable toxicity, or loss of clinical benefit. Patients in the combined radiotherapy arm required hyperfractionated high-dose (54 Gy) radiotherapy twice daily for residual disease in the chest. Each patient will be followed for approximately 2 years.

Interventions

• Radiation High-dose Hyperfractionated Simultaneous Integrated Boost Radiotherapy
  Twice-daily thoracic radiotherapy at a dose of 54 Gy in 30 fractions with IMRT and VMAT
• Drug atezolizumab or durvalumab
  atezolizumab 1200 mg Q3W or durvalumab 1500 mg Q4W

Primary outcome measures

• Overall survival (OS) [Time frame: From randomization to the date of death due to any cause, assessed up to 4 years]

Secondary outcome measures (5)

• Progression-free survival (PFS) [Time frame: From randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 4 years]
• Landmark analyses of survival [Time frame: 1-year and 2-year landmark analysis of OS and 6-month and 1-year landmark analysis of PFS]
• Best overall response (BOR) [Time frame: Up to 4 years]
• Confirmed objective response rate (cORR) [Time frame: Up to 4 years]
• Incidence and severity of adverse events [Time frame: From randomization to 30 days after the end of study treatment]

Eligibility criteria

Inclusion criteria

• Fully informed written consent.
• Age ≥ 18 years.
• Confirmed Extensive Stage Small Cell Lung Cancer (ES-SCLC).
• ECOG PS 0-1.
• No previous systemic therapy except for induction immunochemotherapy for ES-SCLC.
• Partial response or stable disease after 4-6 cycles of induction immunochemotherapy (PD-L1 inhibitor + cisplatin/carboplatin + etoposide). No more than 28 days between last tumor assessment before randomization and randomization.
• Eligible for thoracic radiotherapy as assessed by the radiotherapy physician (The dose limits predicted for the organs at risk are as follows: bilateral lung V20 ≤ 25%, V5 ≤ 48%).
• Patients with stable, asymptomatic CNS metastases are allowed.
• Adequate bone marrow, renal function, and hepatic function.
• Male or female patients of childbearing potential volunteered to use effective contraception during the study and within 6 months of the last dose of study drug.

Exclusion criteria

• Prior thoracic radiotherapy.
• History of interstitial lung disease (including but not limited to idiopathic pulmonary fibrosis), pneumonitis, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Positive testing for hepatitis B virus surface antigen (HBV sAg), hepatitis C virus ribonucleic acid (HCV RNA), or human immunodeficiency virus (HIV).
• Leptomeningeal metastasis.
• Uncontrolled tumor-related pain.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
• Malignancies other than NSCLC within 5 years prior to enrollment, with the exception of those treated with expected curative outcome.
• Active or history of autoimmune disease or immune deficiency.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to enrollment, unstable arrhythmias, or unstable angina.
• Major surgical procedure other than for diagnosis within 4 weeks prior to enrollment or anticipation of need for a major surgical procedure during the course of the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06719336 · STONE-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗