Chemo-immunotherapy Induction Followed by Hypo-radiotherapy in LA-NSCLC(CHIC) — CHIC  

Lung Cancer, Non-small Cell Clinical Trial

Official title: Chemotherapy and Immunotherapy Induction Followed by Hypo-radiotherapy and Immunotherapy Maintenance in Locally Advanced NSCLC

Status Active, not recruiting

Clinical Trial Summary

For unresectable locally advanced non-small cell lung cancer (LA-NSCLC), the standard treatment at present is concurrent chemoradiation therapy (CCRT) followed by durvalumab consolidation therapy. The PACIFIC study indicated a significant benefit in progression-free survival (PFS) and overall survival (OS). Notably, the PACIFIC trial only evaluated patients who had received concurrent chemoradiotherapy. Many patients are unable to tolerate concurrent chemoradiotherapy because of a poor Eastern Cooperative Oncology Group (ECOG) performance status and a high radiation pneumonitis risk for large tumors. Sequential chemoradiotherapy is therefore widely used in clinical practice for patients who cannot tolerate. In the preimmunotherapy era, CCRT showed a significant benefit in OS compared with sequential chemoradiation therapy, with an absolute improvement of 4.5% (from 10.6% to 15.1%) at 5 years. In the immunotherapy era, neoadjuvant immunotherapy plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. Therefore, it is necessary to evaluate the ability of sequential immuno-chemotherapy followed by radiotherapy in patients with unresectable LA-NSCLC.

Moreover, locoregional recurrence still remain the major causes of treatment failure in the immunotherapy era. Our previous study showed that patients with stage III NSCLC treated with hypofractionated radiation therapy(hypoRT) in doses up to 60 Gy at 4 Gy per fraction had promising survival and locoregional control rates. HypoRT may also act synergistically with immunotherapy to enhance immune responses. Thus, the investigators want to exploit the survival benefit effect of immuno-chemotherapy plus sequential hypoRT in LA-NSCLC.

Based on these premises the investigators designed a single arm, phase 2 trial to determine the efficacy and safety of combining immunotherapy in association with standard chemotherapy and subsequently with hypoRT, followed by a treatment of maintenance with only immunotherapy.

The study population includes patients with NSCLC not eligible for surgery. The trial aims to evaluate the clinical outcomes, disease control, and toxicities with this regimen.

This study will last approximately 5 years and will include approximately 55 eligible patients.

Clinical Trial Description

The study population includes patients with NSCLC not eligible for surgery. Sample size calculation was based on the GEMSTONE301 study. It was hypothesised that the hypoRT arm would improve the median PFS by 12 months (HR=0.483). A total of 50 events were requested to detect a statistically significant difference with a type I error of 5% and a type II error of 10% in a bilateral setting. Taking into account a lost-to-follow-up rate of about 5%, we planned to enroll 55 patients.

The study consists of 3 parts:

• Part 1: Patients who have received induction immunotherapy plus chemotherapy for 2-6 cycles and met the hypoRT criteria will be enrolled into the study.

• Part 2: patients will be treated with hypofractionated radiation therapy in doses up to 48-60 Gy at 4 Gy per fraction.

• Part 3: patients with partial response or stable disease after part 2 will be eligible for immunotherapy maintenance, for up to 1 years or until disease progression or unacceptable toxicity. ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer, Non-small Cell

• NCT number: NCT05784142
• Study type: Interventional
• Source: Jiangsu Cancer Institute & Hospital
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 27, 2022
• Completion date: December 2027