Adaptive Hypofractionated Radiotherapy for Locally Advanced NSCLC Based on Dynamic Enhanced MRI

Official title

A Randomized Controlled Phase III Study of Adaptive Hypofractionated Radiotherapy Combined With Concurrent Chemotherapy and Consolidative Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer Based on Dynamic Enhanced Magnetic Resonance Imaging

Overview

This study is a randomized phase III trial that aiming to investigate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) guided hypofractionated radiotherapy (hypo-RT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who are planned to receive hypo-RT combined with concurrent chemotherapy and consolidative immunotherapy. Patients will be randomized in a 1:1 ratio into two groups: 1. The study group will undergo adaptive dose-painting hypo-RT based on DCE-MRI. 2. The control group will undergo hypo-RT based on enhanced CT. The treatment-related toxicity, local control and long-term survival will be evaluated compared between MRI-guided and CT-guided hypo-RT.

Interventions

• Radiation DCE-MRI based split-course hypo-RT
  Tumor delineation will be based on DCE-MRI and CT. MRI help define the tumor boundary. Different radiation doses will be delivered based on the Ktrans value of the tumor area on DCE-MRI.
• Radiation CT based split-course hypo-RT
  Tumor delineation will be based on CT. The total dose for both the first and boost courses of hypo-RT to the tumor area will be constant.
• Drug Concurrent chemotherapy
  Concurrent Chemotherapy consists of weekly albumin-bound paclitaxel 50mg/m2, d1 plus cisplatin 25mg/m2，d1.
• Drug Consolidative immunotherapy
  Consolidative PD-1/PD-L1 inhibitors

Primary outcome measures

• treatment-related G2+ respiratory toxicity [Time frame: Recorded from the enrollment to 1 year after the completion of hypo-RT or 3 months after the completion of consolidative immunotherapy]
• progression-free survival rate [Time frame: 2-year]

Secondary outcome measures (4)

• local control rate [Time frame: 2-year]
• overall survival rate [Time frame: 2-year]
• patient reported outcome assessed by QLQ-C30 [Time frame: 2 year]
• patient reported outcome [Time frame: 2 year]

Eligibility criteria

Inclusion criteria

• Male or female aged between 18 and 75 years old.
• Patients must have histological or cytological confirmation of locally advanced, unresectable (stage III) non-small cell lung cancer (NSCLC).
• No prior radiation therapy or surgery.
• Expected life expectancy of at least 12 weeks.
• World Health Organization (WHO) performance status score of 0 or 1.
• Able to undergo magnetic resonance imaging (MRI) examination.
• Organ and bone marrow function meeting the following criteria: Forced expiratory volume in 1 second (FEV1) ≥ 800 ml; Absolute neutrophil count ≥ 1.5 × 10\^9/L; Platelets ≥ 100 × 10\^9/L; Hemoglobin ≥ 9.0 g/dL; Serum creatinine clearance rate calculated by the Cockcroft-Gault formula ≥ 50 mL/min (Cockcroft and Gault 1976); Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN); Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times ULN.

Exclusion criteria

• Contraindications to MRI examination.
• Concurrent participation in another clinical study, unless it is an observational (non-interventional) clinical study.
• Histological type of mixed small cell and non-small cell lung cancer.
• The presence of sensitive EGFR mutations or ALK rearrangements.
• Major surgery performed within 4 weeks prior to entering the study (excluding vascular access).
• History or occurrence of autoimmune disease within the past 2 years.
• Active or history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of organ transplantation requiring immunosuppressive therapy.
• Average QT interval (QTc) ≥ 470 ms calculated from 3 ECG cycles using Bazett's correction.
• Uncontrolled comorbidities, including but not limited to persistent or active infection, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmia, active peptic ulcer disease or gastritis, active bleeding disorder, human immunodeficiency virus (HIV), or psychiatric/social situations that would limit compliance with study requirements or impair the ability to provide written informed consent.
• Active tuberculosis.
• Receipt of a live attenuated vaccine within 30 days prior to the start of the study.
• History of another primary malignancy within 5 years, excluding adequately treated basal or squamous cell skin cancer or in situ cervical cancer.
• Pregnant or breastfeeding women; or males and females of reproductive potential not using effective contraception.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT06545747 · A2024-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗