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 histologically (Biopsy) confirmed MPM
- N0 or N1 and M0 disease
- Patient and responsible clinician 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
Exclusion criteria:
- Presence of metastatic or contralateral disease
- 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 new effusion that is not amenable to drainage
- WHO Performance Status ≥ 2
- Women who are pregnant or breast feeding
- History of other malignancy, with some exceptions
Duration of recruitment:
3 years
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