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

NCT06719336 | Not Yet Recruiting Phase 3

• 1 other identifier: STONE-001
• Study Type: interventional
• Target: 182
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Extensive-stage Small Cell Lung Cancer

Keywords

Extensive-stage small cell lung cancer; Thoracic consolidation radiotherapy; Immune Therapy

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  From randomization to the date of death due to any cause, assessed up to 4 years

Secondary Outcomes (5)

• 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)

  Up to 4 years

• Confirmed objective response rate (cORR)

  Up to 4 years

• Incidence and severity of adverse events

  From randomization to 30 days after the end of study treatment

Study Arms (2)

Addition of thoracic consolidation radiotherapy to the maintenance therapy with PD-L1 inhibitor

EXPERIMENTAL

Radiation: High-dose Hyperfractionated Simultaneous Integrated Boost Radiotherapy; Drug: atezolizumab or durvalumab

Maintenance therapy with PD-L1 inhibitor

ACTIVE COMPARATOR

Drug: atezolizumab or durvalumab

Interventions

High-dose Hyperfractionated Simultaneous Integrated Boost Radiotherapy RADIATION

Twice-daily thoracic radiotherapy at a dose of 54 Gy in 30 fractions with IMRT and VMAT

Addition of thoracic consolidation radiotherapy to the maintenance therapy with PD-L1 inhibitor

atezolizumab or durvalumab DRUG

atezolizumab 1200 mg Q3W or durvalumab 1500 mg Q4W

Addition of thoracic consolidation radiotherapy to the maintenance therapy with PD-L1 inhibitor; Maintenance therapy with PD-L1 inhibitor

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Anhui Shi, MD: lead

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

atezolizumab; 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

Anhui Shi

CONTACT

+8601088196087; anhuidoctor@163.com

Jun Zhao

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician of Radiotherapy Department

Study Record Dates

• First Submitted: December 2, 2024
• First Posted: December 5, 2024
• Study Start: December 16, 2024
• Primary Completion (Estimated): December 16, 2028
• Study Completion (Estimated): December 16, 2028
• Last Updated: December 5, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Available after publication
• Access Criteria: Request by email to PI