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

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Extensive-stage Small Cell Lung Cancer
• Intervention / Treatment: Radiation: High-dose Hyperfractionated Simultaneous Integrated Boost Radiotherapy; Drug: atezolizumab or durvalumab

• Study Type: Interventional
• Enrollment (Estimated): 182
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jun Zhao
• Study Contact Backup: Name: Anhui Shi; Phone Number: +8601088196087; Email: anhuidoctor@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Fully informed written consent.
2. Age ≥ 18 years.
3. Confirmed Extensive Stage Small Cell Lung Cancer (ES-SCLC).
4. ECOG PS 0-1.
5. No previous systemic therapy except for induction immunochemotherapy for ES-SCLC.
6. 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.
7. 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%).
8. Patients with stable, asymptomatic CNS metastases are allowed.
9. Adequate bone marrow, renal function, and hepatic function.
10. 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:

1. Prior thoracic radiotherapy.
2. 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.
3. Positive testing for hepatitis B virus surface antigen (HBV sAg), hepatitis C virus ribonucleic acid (HCV RNA), or human immunodeficiency virus (HIV).
4. Leptomeningeal metastasis.
5. Uncontrolled tumor-related pain.
6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
7. Malignancies other than NSCLC within 5 years prior to enrollment, with the exception of those treated with expected curative outcome.
8. Active or history of autoimmune disease or immune deficiency.
9. 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.
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Addition of thoracic consolidation radiotherapy to the maintenance therapy with PD-L1 inhibitor	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
Active Comparator: Maintenance therapy with PD-L1 inhibitor	Drug: atezolizumab or durvalumab; atezolizumab 1200 mg Q3W or durvalumab 1500 mg Q4W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	From randomization to the date of death due to any cause, assessed up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)		From randomization to any documented progression or death due to any cause, whichever occurs first, assessed up to 4 years
Landmark analyses of survival		1-year and 2-year landmark analysis of OS and 6-month and 1-year landmark analysis of PFS
Best overall response (BOR)	BOR is the percentage of participants who have a CR or a PR, as determined by investigators according to RECIST v1.1.	Up to 4 years
Confirmed objective response rate (cORR)	cORR is defined as either a confirmed CR or PR on two consecutive evaluations ≥ 4 weeks apart, as determined by investigators according to RECIST v1.1.	Up to 4 years
Incidence and severity of adverse events		From randomization to 30 days after the end of study treatment

Collaborators and Investigators

• Sponsor: Anhui Shi, MD

Study record dates

Study Major Dates

• Study Start (Estimated): December 16, 2024
• Primary Completion (Estimated): December 16, 2028
• Study Completion (Estimated): December 16, 2028

Study Registration Dates

• First Submitted: December 2, 2024
• First Submitted That Met QC Criteria: December 3, 2024
• First Posted (Estimated): December 5, 2024

Study Record Updates

• Last Update Posted (Estimated): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Immune Therapy; Extensive-stage small cell lung cancer; Thoracic consolidation radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Durvalumab; Atezolizumab
• Other Study ID Numbers: STONE-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD related to article disclosure data
• IPD Sharing Time Frame: Available after publication
• IPD Sharing Access Criteria: Request by email to PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No