Hemithoracic Irradiation With Proton Therapy in Malignant Pleural Mesothelioma

Malignant Pleural Mesothelioma Clinical Trial

— HIT-Meso  

Official title:

Hemithoracic Irradiation With Proton Therapy in Malignant Pleural Mesothelioma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05655078
• Other study ID #: UCL/148232
• Secondary ID: MCTA22F\7
• Status: Recruiting
• Phase: N/A
• Start date: March 28, 2024
• Est. completion date: September 30, 2029

Study information

• Verified date: April 2024
• Source: University College, London
• Contact: Pip Patrick
• Phone: 020 7679 9056
• Email: ctc.hit-meso[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 148
• Est. completion date: September 30, 2029
• Est. primary completion date: March 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Malignant Pleural Mesothelioma
• Mesothelioma
• Mesothelioma, Malignant

Intervention

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).

Locations

Country	Name	City	State
United Kingdom	University College London Hospital	London
United Kingdom	Queen Alexandra Hospital	Portsmouth

Sponsors (4)

Lead Sponsor	Collaborator
University College, London	Asthma + Lung UK, Mesothelioma UK, University of Sheffield

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	Defined as the time from randomisation to the date of disease progression	From randomisation up to 2 years of follow up
Primary	Overall survival	defined as the time from randomisation to the date of death from any cause.	From randomisation up to 2 years of follow up
Secondary	Number of PBT-related adverse events as assessed by CTCAE v5.0	AEs related to proton beam therapy will be collected	From start of PBT up to 2 years of follow up, for long term effects
Secondary	The EORTC quality of life questionnaire (QLQ), EORTC QLQ-C30 score, scale of 0-100.	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
Secondary	ED-5D-5L score	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
Secondary	Participant reported healthcare resource use from information collected on Client Service Receipt Inventory (CSRI)	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
Secondary	Measurement of costs in economic evaluations using iMTA Valuation of Informal Care (iVICQ) questionnaire	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