Hemithoracic Irradiation With Proton Therapy in Malignant Pleural Mesothelioma (HIT-Meso)

March 27, 2026 updated by: University College, London
Phase III randomised-controlled trial for patients with unilateral malignant pleural mesothelioma (MPM).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

148

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Barrow in Furness, United Kingdom, LA14 4LF
        • Recruiting
        • Furness General Hospital
        • Contact:
        • Principal Investigator:
          • Amy Ford
      • Bodelwyddan, United Kingdom, LL18 5UJ
        • Recruiting
        • Betsi Cadwaladr University Health Board -Glan Clwyd Hospital
        • Contact:
        • Principal Investigator:
          • Angel Garcia
      • Bristol, United Kingdom, BS105NB
        • Recruiting
        • Southmead Hospital
        • Principal Investigator:
          • Nick Maskell
        • Contact:
      • Cambridge, United Kingdom, CB20QQ
        • Recruiting
        • Addenbrooke's Hospital
        • Principal Investigator:
          • Huiqi Yang
        • Contact:
      • Cardiff, United Kingdom
        • Recruiting
        • Velindre Cancer Centre
        • Principal Investigator:
          • Paul Shaw
        • Contact:
      • Chelmsford, United Kingdom, CM1 7ET
        • Recruiting
        • Broomfield Hospital
        • Contact:
        • Principal Investigator:
          • Thomas Sarkodie
      • Hull, United Kingdom, HU165JQ
        • Recruiting
        • Queens Centre, Castle Hill Hospital
        • Contact:
        • Principal Investigator:
          • Dr Louise Karsera
      • Lancaster, United Kingdom, LA1 4RP
        • Recruiting
        • Royal Lancaster Hospital
        • Contact:
        • Principal Investigator:
          • Amy Ford
      • Leeds, United Kingdom, LS97TF
      • Leicester, United Kingdom, LE1 5WW
      • Liverpool, United Kingdom, L78YA
      • London, United Kingdom, EC1A 7BE
        • Recruiting
        • St Bartholomew's Hospital
        • Contact:
        • Principal Investigator:
          • Pandora Rudd
      • London, United Kingdom
        • Recruiting
        • University College London Hospital
        • Principal Investigator:
          • Crispin Hiley
        • Contact:
      • Maidstone, United Kingdom, ME169QQ
      • Manchester, United Kingdom, M23 9LT
        • Recruiting
        • Wythenshawe Hospital
        • Principal Investigator:
          • Paul Taylor
        • Contact:
      • Manchester, United Kingdom, M20 4BX
        • Active, not recruiting
        • Christie Hospital
      • Newcastle upon Tyne, United Kingdom, NE77DN
        • Recruiting
        • Freeman Hospital
        • Contact:
        • Principal Investigator:
          • Helen Turnbull
      • Sheffield, United Kingdom, S102SJ
        • Recruiting
        • Weston Park Cancer Centre
        • Principal Investigator:
          • Tathagata Das
        • Contact:
      • Torquay, United Kingdom, TQ2 7AA
        • Recruiting
        • Torbay Hospital
        • Principal Investigator:
          • Louise Medley
        • Contact:
    • East Sussex
      • Eastbourne, East Sussex, United Kingdom
        • Recruiting
        • East Sussex Healthcare NHS Trust - Eastbourne Hospital
        • Contact:
      • Saint Leonards-on-Sea, East Sussex, United Kingdom
        • Recruiting
        • East Sussex Healthcare NHS Trust - Conquest Hospital
        • Contact:
    • England
      • Reading, England, United Kingdom, RG15AN
    • Essex
      • Southend, Essex, United Kingdom, SS0 0RY
        • Recruiting
        • Southend University Hospital
        • Principal Investigator:
          • Rafiqul Islam
        • Contact:
    • Hampshire
      • Portsmouth, Hampshire, United Kingdom
    • Norfolk
      • Kings Lynn, Norfolk, United Kingdom, PE30 4ET

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  • Patients ≥18 years of age, with biopsy confirmed MPM and histological subtyping (epithelioid or non-epithelioid)
  • N0 or N1 and M0 disease
  • Written informed consent
  • Patient and local/regional MDT opt for active surveillance and deferral of SACT until clinical or radiological progression
  • WHO Performance Status 0-1
  • Disease confined to one hemithorax based on CT assessment

  • Adequate pulmonary function

    • ≥ 40% predicted post-FEV1;
    • ≥ 40% predicted DLCO/TLCO
  • Agreement to travel to either proton beam therapy centres (i.e. UCLH or The Christie) if randomised to arm 2
  • Agreement to be followed up at a local HIT-Meso trial site
  • Patient likely able to complete PBT planning based on local assessment

Exclusion criteria:

  • Presence of metastatic or contralateral disease
  • Cytological diagnosis and/or undetermined histological subtype
  • Prior thoracic radiotherapy, chemotherapy, immunotherapy for MPM
  • Prior radical surgery for MPM (extrapleural pneumonectomy or extended pleurectomy decortication or pleurectomy decortication)
  • Initial systemic therapy or surgery is required and the patient and local/regional MDT do not opt for active surveillance
  • Involvement of contralateral or supraclavicular lymph nodes
  • T4 disease with invasion of the myocardium
  • N2 and/or M1 disease
  • Presence of new effusion that is not amenable to drainage
  • WHO Performance Status ≥ 2
  • Women who are pregnant or breast feeding
  • Current or previous malignant disease which may impact on the patient's life expectancy
  • Patient fitted with a pacemaker or implantable cardioverter-defibrillator (ICD)\
  • Diagnosis of clinically significant interstitial lung disease (ILD), excluding mild fibrosis or incidental findings
  • Chronic non-malignant disease with an estimated three-year survival rate of less than 20%
  • Patient with prior thoracic / abdominal radiotherapy for malignancy who was not discussed with sponsor before recruitment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard of care
MPM participants who are on the standard of care watch and wait approach i.e. immediate treatment not suitable. Participants will have follow-up for 2 years (3 monthly in year 1, 4 monthly in year 2).
Experimental: Proton beam therapy
MPM participants to receive 5 weeks of proton beam therapy to the hemithorax. Following completion of treatment participants will have follow-up at the referring centre for 2 years (3 monthly in year 1, 4 monthly in year 2).
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: From randomisation up to 2 years of follow up
Defined as the time from randomisation to the date of disease progression
From randomisation up to 2 years of follow up
Overall survival
Time Frame: From randomisation up to 2 years of follow up
defined as the time from randomisation to the date of death from any cause.
From randomisation up to 2 years of follow up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of PBT-related adverse events as assessed by CTCAE v5.0
Time Frame: From start of PBT up to 2 years of follow up, for long term effects
AEs related to proton beam therapy will be collected
From start of PBT up to 2 years of follow up, for long term effects
The EORTC quality of life questionnaire (QLQ), EORTC QLQ-C30 score, scale of 0-100.
Time Frame: From randomisation up to 2 years of follow up

Participant reported quality of life outcomes. The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / quality of life (QoL scale), and six single items. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
From randomisation up to 2 years of follow up
ED-5D-5L score
Time Frame: From randomisation up to 2 years of follow up
Participant reported quality of life outcomes. The questionnaire comprises descriptive systems: mobility, self care, usual activities, pain/discomfort, anxiety/depression; scored from, level 1 to 5; level 1 indicating no problem and level 5 indicating unable to/extreme problems. There is also a scale from 0-100 to describe health status, 100 being the best health the patient can imagine, 0 being the worst health they can imagine.
From randomisation up to 2 years of follow up
Participant reported healthcare resource use from information collected on Client Service Receipt Inventory (CSRI)
Time Frame: From randomisation up to 2 years of follow up
A tool used to collect participant reported information on the range of healthcare services and supports study participants may use, to calculate the rate of service usage to evaluate resource use as part of health economic analysis.
From randomisation up to 2 years of follow up
Measurement of costs in economic evaluations using iMTA Valuation of Informal Care (iVICQ) questionnaire
Time Frame: From randomisation up to 2 years of follow up
Scoring (no scale) to evaluate health economics comparing PBT vs SOC surveillance and other SOC treatments for malignant pleural mesothelioma.
From randomisation up to 2 years of follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Collaborators

University of Sheffield
Asthma + Lung UK
Mesothelioma UK

Investigators

  • Principal Investigator: Crispin Hiley, University College, London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 28, 2024

Primary Completion (Estimated)

March 31, 2029

Study Completion (Estimated)

September 30, 2029

Study Registration Dates

First Submitted

November 11, 2022

First Submitted That Met QC Criteria

December 14, 2022

First Posted (Actual)

December 16, 2022

Study Record Updates

Last Update Posted (Actual)

March 30, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCL/148232
  • MCTA22F\7 (Other Grant/Funding Number: Asthma _ Lung UK)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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