Hemithoracic Irradiation With Proton Therapy in Malignant Pleural Mesothelioma

NCT ID: NCT05655078

Last Updated: 2024-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

148 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-28

Study Completion Date

2029-09-30

Brief Summary

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

Detailed Description

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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

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Malignant Pleural Mesothelioma

Keywords

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Proton beam therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Control arm (standard of care) vs experimental arm (proton beam therapy) in 1:1 randomisation
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type NO_INTERVENTION

No interventions assigned to this group

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).

Group Type EXPERIMENTAL

Proton beam therapy

Intervention Type RADIATION

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).

Interventions

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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).

Intervention Type RADIATION

Eligibility Criteria

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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 of systemic 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 The Christie) if randomised to arm 2
* Agreement to be followed up at a local HIT-Meso trial 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; Exception: (a) Subjects who have been successfully treated and are disease-free for 3 years, (b) a history of treated non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in stable remission, or (e) indolent prostate cancer requiring no or only anti-hormonal therapy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Asthma + Lung UK

UNKNOWN

Sponsor Role collaborator

Mesothelioma UK

UNKNOWN

Sponsor Role collaborator

University of Sheffield

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Crispin Hiley

Role: PRINCIPAL_INVESTIGATOR

University College, London

Locations

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Royal Berkshire Hospital

Reading, England, United Kingdom

Site Status RECRUITING

Southend University Hospital

Southend, Essex, United Kingdom

Site Status RECRUITING

Queen Alexandra Hospital

Portsmouth, Hampshire, United Kingdom

Site Status RECRUITING

Queen Elizabeth Hospital, King's Lynn

Kings Lynn, Norfolk, United Kingdom

Site Status RECRUITING

Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status RECRUITING

Velindre Cancer Centre

Cardiff, , United Kingdom

Site Status RECRUITING

Broomfield Hospital

Chelmsford, , United Kingdom

Site Status RECRUITING

St Bartholomew's Hospital

London, , United Kingdom

Site Status RECRUITING

University College London Hospital

London, , United Kingdom

Site Status RECRUITING

Christie Hospital

Manchester, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Wythenshawe Hospital

Manchester, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Klara Sinalova

Role: CONTACT

Phone: 020 7679 9826

Email: [email protected]

Aoife Walker

Role: CONTACT

Phone: 020 3108 5363

Email: [email protected]

Facility Contacts

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Lilian Cheung

Role: primary

Rafiqul Islam

Role: primary

Hannah Bainbridge

Role: primary

Kamalram Thippu Jayaprakash

Role: primary

Huiqi Yang

Role: primary

Paul Shaw

Role: primary

Thomas Sarkodie

Role: primary

Pandora Rudd

Role: primary

Crispin Hiley

Role: primary

Paul Taylor

Role: primary

Other Identifiers

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MCTA22F\7

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

UCL/148232

Identifier Type: -

Identifier Source: org_study_id