NCT05655078

Hemithoracic Irradiation With Proton Therapy in Malignant Pleural Mesothelioma

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 148 (estimated)
• Sponsor: University College, London · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Phase III randomised-controlled trial for patients with unilateral malignant pleural mesothelioma (MPM).

Detailed description

Study design: Randomised phase III clinical trial for patients with unilateral MPM. Primary endpoint: Progression free survival (PFS) and overall survival (OS), defined as the time from randomisation to the date of progression and death from any cause. Secondary Endpoints: Safety and Tolerability, Health related Quality of Life (QOL): EuroQoL EQ-5D-3L, Locoregional Control. Randomisation and stratification: 1:1 randomisation. Patients with be stratified for histology (epithelioid versus non-epithelioid), potential PBT centre (UCLH or The Christie) , laterality (left or right sided) and time since diagnosis (\<1 year or \> 1 year) Treatment: Experimental Arm: Patients in the experimental arm will receive PBT to the hemithorax to a dose of 50Gy in 25 fractions with a boost to 60Gy for the visible tumour (gross tumour volume-GTV). Treatment is given daily Monday-Friday over 5 weeks. Following completion of treatment in the experimental arm patients will have 2 years of follow-up from time of randomisation at the local recruiting/referring centre. Control Arm: The patients in the control arm would be under standard of care surveillance i.e. "watch and wait", with no treatment or other intervention. Patients will have 2 years of follow-up from time of randomisation at the local recruiting/referring centre. If the disease progresses, the patient will receive SOC treatment i.e. immunotherapy with nivolumab and ipilimumab, or chemotherapy at the clinician's discretion. Statistical analysis plan: The sample size is 148 patients (74 patients per arm). This is to detect a OS hazard ratio of 0.58, equivalent to an improvement in 2-year OS from 30% to 50%, with 85% power and 5% two-sided alpha. Recruitment to complete in 3 years across 20 UK centres with 2 years of additional follow-up and up to 5% dropout. Interim analyses for OS efficacy will be performed when 50, 75 and 110 patients have been randomised at around 1.5, 2.0 and 2.5 years respectively. Using a fixed-sequence approach, a difference for OS will only be tested if the co-primary endpoint of PFS is statistically significant (p\<0.05); N=148 will provide \>85% power to detect a PFS hazard ratio of 0.58 accounting for up to 10% dropout.

Conditions

• Malignant Pleural Mesothelioma

Interventions

Type	Name	Description
RADIATION	Proton beam therapy	5 weeks (Mon-Fri) of proton beam treatment to the hemithorax to a dose of 50Gy in 25 fractions with a boost to 60Gy for the visible tumour (gross tumour volume-GTV).

Timeline

• Start date: 2024-03-28
• Primary completion: 2029-03-31
• Completion: 2029-09-30
• First posted: 2022-12-16
• Last updated: 2026-03-30

Locations

25 sites across 1 country: United Kingdom