NCT06816966

Chemotherapy-immunotherapy-based Split-course Adaptive Hypofractionated Radiotherapy for Extensive-stage SCLC

Systemic Treatments (Chemotherapy-immunotherapy) Based Split-course Adaptive Hypofractionated Radiotherapy for Extensive-stage SCLC: CISART Study

• Status: Enrolling By Invitation
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Sponsor: Fujian Medical University Union Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is a prospective, single-arm, phase Ⅱ trial evaluating the safety and efficacy of Chemotherapy-immunotherapy-based split-course adaptive hypofractionated radiotherapy for extensive-stage SCLC

Detailed description

Small cell lung cancer (SCLC) represents the most aggressive and metastatic form of lung carcinoma, particularly in its extensive stage1. SCLC is initially highly chemotherapy sensitive, yet it is paradoxically characterized by nearly ubiquitous metastatic relapse and secondary chemoresistance2. Despite the incorporation of immune checkpoint inhibitors (ICIs) has led to improvements in survival, the benefit is only modest, with an overall survival (OS) improvement of approximately 3-5 months, and the median OS has yet to surpass two years3. This highlights the need for innovative combination strategies. Although consolidative thoracic radiotherapy (TRT) has shown promise in improving local control and two-year survival in ES-SCLC patients with residual intrathoracic disease after first-line chemotherapy 4-6, the efficacy of TRT remains uncertain in the era of immunotherapy. RAPTOR (NCT04402788) is an ongoing phase Ⅱ/Ⅲ trial evaluating the addition of TRT to the usual maintenance therapy with atezolizumab in ES-SCLC patients with a partial response (PR)/stable disease (SD). Given that TRT is administered exclusively to selected patients who have demonstrated a positive response to first-line treatment without disease progression（PD）, a significant proportion of patients are ineligible for TRT due to disease progression. ES-SCLC typically presents with a high tumor burden and bulky thoracic lymph nodes which are the most dominant failure site after chemotherapy or chemoimmunotherapy. According to multiregion sequencing, it is reported that treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas a multitude of subclones driven by the most recent common ancestor at clinically overt recurrence, which markedly increases spatial and intratumour heterogeneity7. Considering of initial chemotherapy and radiation sensitivity of SCLC and potential synergistic effects of radiotherapy and immunotherapy, investigator hypothesized that add primary thoracic site RT to first-line chemoimmuntherapy may help killing more clonal tumor cells and enhancing systemic disease control. Whereas it must balance the specific toxicity risks of combined therapy to avoid systemic therapy interruption. Based on the findings of split-course SBRT based on systemic therapy (3S) in for locally advanced rectal cancer（NCT05176964）and borderline resectable pancreatic cancer (NCT04289792) in the institution，this study designed as a single-centre, single- arm, prospective phase Ⅱ trial in subjects with treatment- naïve ES-SCLC to treated with EP regimen chemotherapy, PD-L1/1 inhabitors and split-course hypofractionated radiotherapy (SCHR) as first-line therapy. Patients will be synchronously treated with etoposide/platinum (E/P) doublet plus ICIs and SCHR (4-6 fractions×5 Gy). Chemotherapy and ICIs start on days 1,2,3 and day 8 of every 21-day cycle, respectively. A single dose of 5 Gy radiotherapy may be administered either during a three-day chemotherapy cycle or within a two-day window preceding or following the cycle, taking into account the necessary time for radiotherapy planning and potential scheduling constraints such as weekends.Split-course hypofractionated radiotherapy will be response-adaptively delivered in 4-6 treatments to primary lesion, thoracic lymph nodes in thoracic cavity, adjacent involved supraclavicular and cervical lymph nodes because of shrinkage of bulky tumor. Chemotherapy interval spanning weeks not only allow for greater recovery of normal tissue following an injury from initial bulky-area radiation, but may also maximize potential synergies resulting from concomitant immune-oncology approaches.

Conditions

• Small-cell Lung Cancer

Interventions

Type	Name	Description
RADIATION	split-course adaptive hypofractionated radiotherapy	Each treatment cycle comprises a solitary radiotherapy session, which allows for its integration with chemotherapy and immunotherapy. The radiotherapy sessions are scheduled at three-week intervals, thereby affording extended recovery periods for normal tissues. An adaptive radiotherapy plan is implemented for each cycle, enabling precise adjustments to the treatment target area in response to the reduction in tumor volume.

Timeline

• Start date: 2023-12-26
• Primary completion: 2026-10-31
• Completion: 2028-10-31
• First posted: 2025-02-10
• Last updated: 2025-02-10

Locations

1 site across 1 country: China