NCT06187740

Thoracic Consolidation Radiotherapy for ES-SCLC Treated With Chemo-immunotherapy

A Phase I Dose Escalation Study of Thoracic Consolidation Radiotherapy for Extensive-stage Small Cell Lung Cancer Patients Treated With Chemo-immunotherapy

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study intends to recruit ES-SCLC patients with response to standard first-line chemo-immunotherapy to assess the safety of receiving different doses of consolidative thoracic radiotherapy.

Detailed description

Approximately two-thirds of Small-cell lung cancer (SCLC) patients are in the extensive stage (Extensive-Stage SCLC, ES-SCLC) at the time of diagnosis, and the 5-year survival rate of these patients is less than 5%. Before the immunotherapy era, the standard first-line treatment for ES-SCLC had been platinum-based chemotherapy regimens combined with etoposide. Since treatment failure patterns revealed high probability of residual thoracic disease and high risk of progression of thoracic lesions after ES-SCLC chemotherapy, previous studies suggest that thoracic consolidation radiotherapy in ES-SCLC patients who are sensitive to first-line chemotherapy can reduce the risk of thoracic recurrence and improve overall survival time. Slotman et al. further conducted a phase III randomized controlled clinical study to explore the application of thoracic consolidation radiotherapy in ES-SCLC (CREST study). The CREST study results showed that in ES-SCLC patients who responded to chemotherapy and had residual thoracic lesions, thoracic residual lesion radiotherapy (30 Gy/1 0Fx) combined with prophylactic brain radiotherapy could reduce the risk of thoracic recurrence by 50% and increase the 2-year survival rate from 3% to 13%. With the advent of the era of immunotherapy, the IMpower133 trial showed that the combination of atezolizumab and chemotherapy prolonged the median overall survival time of ES-SCLC patients compared with the chemotherapy alone group. In the CASPIAN study, the combination of dulvumab and chemotherapy also resulted in a survival benefit. The ASTRUM-005 study using PD-1 monoclonal antibody Serplulimab in combination with chemotherapy also achieved prolonged overall survival. Although the overall median survival of ES-SCLC is prolonged after immunotherapy in combination with chemotherapy, patients who truly achieve long-term survival are still limited, with a 3-year OS rate of about 15% - 20%. Accordingly, it is necessary to explore effective methods to combine radiotherapy and maximize the benefit population of immunotherapy in ES-SCLC. Failure pattern analysis revealed that, consistent with the era of non-immunotherapy, the main progression phenotype in patients receiving first-line chemotherapy + immunotherapy remained thoracic progression, suggesting that sequential thoracic consolidation radiotherapy is still likely to achieve clinical benefit in ES-SCLC patients receiving chemo-immunotherapy. Immunotherapy combined with concurrent chemoradiotherapy has shown good safety and survival benefit in limited-stage SCLC. In non-small cell lung cancer (NSCLC), the safety of sequential immunotherapy after thoracic chemoradiotherapy has also been verified. However, there is a lack of prospective studies to investigate the safety of sequential thoracic consolidation radiotherapy after first-line immunochemotherapy in ES-SCLC patients. At present, the widely used ES-SCLC thoracic consolidation radiotherapy regimen is based on the 30 Gy/1 0Fx dose fractionation of CREST study. At the same time, it has been shown that increasing the dose of single radiotherapy within a certain range helps to increase the production of immunogenic death by tumor cells, that is, more tumor-specific antigens that can be recognized by the immune system are produced during the induction of tumor cell death. Therefore, this study intends to perform a dose escalation study based on 30 Gy/10Fx dose fractionation and assess the safety of this treatment mode.

Conditions

• Small Cell Lung Cancer Extensive Stage

Interventions

Type	Name	Description
RADIATION	thoracic radiotherapy	Thoracic radiotherapy should begin within 42 days after the end of the last chemotherapy at an initial dose of 30 Gy in 10 fractions (3 patients). Dose escalation will start after acceptable safety was observed, first at: 35 Gy/10 Fx(3 patients), then to the next dose group: 40 Gy/10 Fx(22 patients). Radiotherapy was administered between two immunotherapy doses (3 weeks interval) to avoid thoracic radiotherapy on the same day with immunotherapy.

Timeline

• Start date: 2023-12-01
• Primary completion: 2025-06-30
• Completion: 2025-12-31
• First posted: 2024-01-03
• Last updated: 2024-01-09

Locations

1 site across 1 country: China