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

Plain English Summary

Adaptive Hypofractionated Radiotherapy for Locally Advanced NSCLC Based on Dynamic Enhanced MRI is a Phase 3 clinical trial sponsored by Sun Yat-sen University studying Non-small Cell Lung Cancer. This trial tests a new way to guide radiation therapy for advanced lung cancer using detailed MRI scans to target the tumor more precisely. It is for patients with locally advanced, non-resectable non-small cell lung cancer who haven't had prior radiation or surgery. Participation involves receiving radiation therapy combined with chemotherapy and immunotherapy, with some patients guided by MRI and others by standard CT scans. The main alternative is standard radiation therapy guided by CT scans, without the advanced MRI-based adaptive targeting. The trial aims to enroll 490 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients aged 18-75 with confirmed locally advanced, unresectable non-small cell lung cancer can join. You cannot join if you have had prior radiation or surgery for this cancer, have contraindications to MRI, or have certain other medical conditions like active infections or uncontrolled heart disease. Good general health, including specific lung function (FEV1), blood counts, kidney, and liver function, is required. This trial is studying Non-small Cell Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how well the treatment controls the cancer locally and how long patients live without their cancer getting worse, aiming for better results with the new MRI-guided approac The specific primary outcome measures are: treatment-related G2+ respiratory toxicity (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 (2-year). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to improve treatment for locally advanced lung cancer by using advanced MRI to personalize radiation doses, potentially leading to better tumor control and fewer side effects. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Non-small Cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This Phase III trial addresses a significant unmet need in locally advanced NSCLC, with potential for improved outcomes if the MRI-guided approach proves superior, offering a competitive edge in advan Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if this MRI-guided radiation therapy is suitable for your specific type and stage of lung cancer. Understand that participation involves regular clinic visits for treatment, scans, and monitoring for side effects. Be prepared for potential side effects from radiation, chemotherapy, and immunotherapy, and report any new or worsening symptoms promptly. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 490 participants

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 Outcomes

• treatment-related G2+ respiratory toxicity (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 (2-year)

Secondary Outcomes

• local control rate (2-year)
• overall survival rate (2-year)
• patient reported outcome assessed by QLQ-C30 (2 year)
• patient reported outcome (2 year)

Full 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.

Trial Locations

• Sun Yat-sen University Cancer Center, Guangzhou, China

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer
• Stage III Lung Cancer
• Lung Cancer
• Thoracic Oncology
• Radiation Oncology
• Medical Oncology
• Chemotherapy
• Immunotherapy
• Targeted Therapy
• Cancer Imaging

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