Hemithoracic irradiation with proton therapy in malignant pleural mesothelioma
Description
Design:
Phase III randomised controlled trial for patients with unilateral malignant pleural mesothelioma
Eligible patients are randomised (1:1) to receive either proton beam therapy (PBT) or standard active surveillance. The study will recruits at sites across the UK, with PBT treatment given at either the Christie Hospital, Manchester, or University College London Hospital.
Treatment:
Arm 1 (control)
Active surveillance and deferral of systemic anti-cancer therapy (SACT) until clinical or radiological progression.
Arm 2 (interventional)
Proton Beam Therapy 50Gy in 25 fractions with an integrated boost to 60Gy to the visible tumour if organs at risk constraints are not exceeded.
Follow up at local referring centre.
Key inclusion/exclusion criteria:
Inclusion criteria:- Patients ≥18 years of age, with biopsy confirmed MPM and histological subtyping (epithelioid or non-epithelioid)
- N0 or N1 and M0 disease
- Patient and local/regional MDT opt for active surveillance, and deferral of SACT until clinical or radiological progression
- Written informed consent
- 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 the PBT site for PBT treatment if randomised to arm 2
- Agreement to be followed up at a local HIT-Meso site
- Patient likely able to complete PBT planning based on local assessment
Exclusion criteria:
- Presence of metastatic or contralateral disease
- Cytological diagnosis and/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 responsible clinician do not opt for active surveillance
- Involvement of contralateral or supraclavicular lymph nodes
- T4 disease with clear invasion of the myocardium
- N2 and/or M1 disease
- Presence of asignificant pleural effusion that is not amenable to aspiration or drainage andis likely to affect radiotherapy planning
- WHO Performance Status ≥ 2
- Women who are pregnant or breast feeding
- Current or previousmalignant disease which may impact on the patient’s life expectancy
- Patient fitted witha pacemaker or implantable cardioverter-defibrillator (ICD)
- Diagnosis ofclinically significant interstitial lung disease (ILD), excluding mild fibrosisor incidental findings
- Chronicnon-malignant disease with an estimated three-year survival rate of less than20%
- Patients with priorthoracic / abdominal radiotherapy for malignancy who were not discussed withsponsor before recruitment
Duration of recruitment:
3 years (April 2024-March 2027)
Aim
- To determine if delivering PBT to the involved hemithorax can improve progression-free survival (PFS) and overall survival (OS)
- To determine if hemithoracic radiotherapy with PBT affects the quality of life of patients with MPM over 2 years
- To determine the relative cost-effectiveness of hemithoracic radiotherapy with PBT in MPM compared with current standard of care therapy over 2 years