Hemithoracic Irradiation With Proton Therapy in Malignant Pleural Mesothelioma

Last updated: December 18, 2024
Sponsor: University College, London
Overall Status: Active - Recruiting

Phase

N/A

Condition

Mesothelioma

Lung Cancer

Treatment

Proton beam therapy

Clinical Study ID

NCT05655078
UCL/148232
MCTA22F\7
  • Ages > 18
  • All Genders

Study Summary

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

Eligibility Criteria

Inclusion

Inclusion criteria:

  • Patients ≥18 years of age, with histologically (biopsy) confirmed MPM

  • N0 or N1 and M0 disease

  • Written informed consent

  • Patient and responsible clinician opt for active surveillance and deferral ofsystemic anti-cancer therapy 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 TheChristie) if randomised to arm 2

  • Agreement to be followed up at a local HIT-Meso trial site

Exclusion

Exclusion criteria:

  • Presence of metastatic or contralateral disease

  • Prior thoracic radiotherapy, chemotherapy, immunotherapy for MPM

  • Prior radical surgery for MPM (extrapleural pneumonectomy or extended pleurectomydecortication or pleurectomy decortication)

  • Initial systemic therapy or surgery is required and the patient and responsibleclinician 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; Exception: (a) Subjects who have been successfullytreated and are disease-free for 3 years, (b) a history of treated non-melanoma skincancer, (c) successfully treated in situ carcinoma, (d) CLL in stable remission, or (e) indolent prostate cancer requiring no or only anti-hormonal therapy.

Study Design

Total Participants: 148
Treatment Group(s): 1
Primary Treatment: Proton beam therapy
Phase:
Study Start date:
March 28, 2024
Estimated Completion Date:
September 30, 2029

Study 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.

Connect with a study center

  • Royal Berkshire Hospital

    Reading, England RG15AN
    United Kingdom

    Active - Recruiting

  • Southend University Hospital

    Southend, Essex SS0 0RY
    United Kingdom

    Active - Recruiting

  • Queen Alexandra Hospital

    Portsmouth, Hampshire
    United Kingdom

    Active - Recruiting

  • Queen Elizabeth Hospital, King's Lynn

    King's Lynn, Norfolk PE30 4ET
    United Kingdom

    Active - Recruiting

  • Addenbrooke's Hospital

    Cambridge, CB20QQ
    United Kingdom

    Active - Recruiting

  • Velindre Cancer Centre

    Cardiff,
    United Kingdom

    Active - Recruiting

  • Broomfield Hospital

    Chelmsford, CM1 7ET
    United Kingdom

    Active - Recruiting

  • St Bartholomew's Hospital

    London, EC1A 7BE
    United Kingdom

    Active - Recruiting

  • University College London Hospital

    London,
    United Kingdom

    Active - Recruiting

  • Christie Hospital

    Manchester, M20 4BX
    United Kingdom

    Site Not Available

  • Wythenshawe Hospital

    Manchester, M23 9LT
    United Kingdom

    Active - Recruiting

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