Identification of Prognostic and Predictive Biomarkers of Toxicity in Patients With Malignant Pleural Mesothelioma and Treated With High Doses of Radiotherapy (MESORTIBO) (MESORTIBO)

Malignant pleural mesothelioma (MPM) is a tumour that originates from the pleural layers (visceral and parietal) that envelop the lungs and the inner wall of the thoracic cage.

In other tumour contexts, numerous studies have demonstrated a synergistic effect between RT and Immune Checkpoint Inhibitors (ICIs), mainly due to immunogenic effects attributed to high doses of RT and ICIs-mediated activation of anti-tumour T lymphocytes.

Both treatments, RT and immunotherapy, have demonstrated a survival advantage in MPM, but are associated with non-negligible pulmonary toxicity. Therefore, the combination of these 2 therapeutic approaches requires a careful assessment of risk factors for the occurrence of toxicity. The identification of circulating biomarkers capable of predicting the onset of severe toxicity induced by radical radiation treatment is an important clinical need in MPM.

This study aims to monitor circulating biomarkers, such as molecules involved in inflammation and oxidative stress and cellular effectors modulated by radiation treatment and potentially associated with the development of toxicity and/or markers of an immunogenic effect of radiotherapy in the peripheral blood of subjects with malignant pleural mesothelioma for treatment with radical hemithoracic radiotherapy.

Study Overview

• Status: Recruiting
• Conditions: Pleural Mesothelioma Malignant

Detailed Description

Malignant pleural mesothelioma (MPM) is a tumour that originates from the pleural layers (visceral and parietal) that envelop the lungs and the inner wall of the thoracic cage.

In other tumour contexts, numerous studies have demonstrated a synergistic effect between RT and Immune Checkpoint Inhibitors (ICIs), mainly due to immunogenic effects attributed to high doses of RT and ICIs-mediated activation of anti-tumour T lymphocytes.

Both treatments, RT and immunotherapy, have demonstrated a survival advantage in MPM, but are associated with non-negligible pulmonary toxicity. Therefore, the combination of these 2 therapeutic approaches requires a careful assessment of risk factors for the occurrence of toxicity. The identification of circulating biomarkers capable of predicting the onset of severe toxicity induced by radical radiation treatment is an important clinical need in MPM.

This study aims to monitor circulating biomarkers, such as molecules involved in inflammation and oxidative stress and cellular effectors modulated by radiation treatment and potentially associated with the development of toxicity and/or markers of an immunogenic effect of radiotherapy in the peripheral blood of subjects with malignant pleural mesothelioma for treatment with radical hemithoracic radiotherapy.

• Study Type: Observational
• Enrollment (Estimated): 52

Contacts and Locations

• Study Contact: Name: Alberto Revelant, MD; Phone Number: 0434 659 159; Email: alberto.revelant@cro.it

Study Locations

• Italy
  • Pordenone
    • Aviano, Pordenone, Italy, 33081
      • Recruiting
      • Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS
      • Contact: Alberto Revelant, MD; Phone Number: 0434 659 159; Email: alberto.revelant@cro.it
      • Principal Investigator: Alberto Revelant, MD
      • Principal Investigator: Elena Muraro, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with non-metastatic MPM previously treated with chemotherapy, undergoing a non-radical long-sparing surgical approach and treated with RT with radical intent (retrospective cohort) or eligible for RT with radical intent (prospective cohort)

Description

Inclusion Criteria:

• Over 18 years of age;
• Ability to understand, accept and sign consent informed;
• Histological diagnosis of malignant pleural mesothelioma;
• Previous administration of chemotherapy;
• Previous non-radical surgical approach (diagnostic thoracoscopy or R1-R2 surgery);
• Subject eligible for or already treated with RT on hemithorax for radical purposes (50 Gy in fractions on hemithorax + possible boost 60 Gy on residual PET+)

Exclusion Criteria:

• Disease not histologically established
• Progression pattern not amenable to radiation treatment (ipsilateral or metastatic intrathoracic extensive disease);
• Metastatic patient at diagnosis.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Retrospective cohort; Patients treated with RT with radical intent from 01 January 2014 to the date of study approval
Prospective cohort; Patients eligible for radical intent radiotherapy treatment radical, from the date of study approval

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between biomarker levels measured at the end of radiation treatment and pulmonary toxicity of grade ≥2 associated with RT developed as an acute (within 6 months) or late (after 6 months) event	Differences in fold change of selected biomarkers, between subjects experiencing or not experiencing acute or late toxicity	up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relation between the severity of radio-induced toxicity and trend of biomarkers associated with it	Evaluation of linear trend of biomarkers fold change in relation with toxicity severity	up to 36 months
Identifying biomarkers associated with lung toxicity potentially predictive of pulmonary fibrosis	Difference in frequencies of selected biomarkers between subgroups of patients with or without pulmonary fibrosis	up to 36 months
Identifying signs of radio-induced immunomodulation among significant changes induced by hemithoracic radical radiotherapy in analysed biomarkers	difference in median values of selected biomarkers before and after treatment	up to 36 months
Association between the levels of biomarkers measured at the end of treatment radiation and overall survival (OS) at 24 months	Relation between overall survival and levels of biomarkers fold change using Cox regression. OS will be defined as time from beginning of the therapy until death from any cause or end of follow-up, whichever comes first.	24 moths after end of treatment
To assess the prognostic potential of basal levels of analysed biomarkers	Relation between OS and pretreatment levels of selected biomarkers. Levels of biomarkers will be dichotomized based on pretreatment median value. Kaplan-Meier method and log rank test will be used. OS will be defined as time from beginning of the therapy until death from any cause or end of follow-up, whichever comes first.	up to 36 months
Association between the levels of biomarkers variation (between baseline and treatment end) and Progression Free Survival (PFS) at 12 months	Relation between PFS and levels of biomarkers fold change compared to pre-treatment value. PFS will be defined as time from beginning of the therapy until objective PD, death or end of follow-up, whichever comes first.	12 months after end of treatment

Collaborators and Investigators

• Sponsor: Centro di Riferimento Oncologico - Aviano
• Investigators: Principal Investigator: Alberto Revelant, MD, Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2024
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): March 15, 2027

Study Registration Dates

• First Submitted: October 3, 2024
• First Submitted That Met QC Criteria: October 9, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 9, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant
• Other Study ID Numbers: CRO-2023-63

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No