Clinical trial NCT06637345: Identification of Prognostic and Predictive Biomarkers of Toxicity in Patients With Malignant Pleural Mesothelioma and Treated With High Doses of Radiotherapy (MESORTIBO)
Official title: Identification of Prognostic and Predictive Biomarkers of Toxicity in Patients With Malignant Pleural Mesothelioma and Treated With High Doses of Radiotherapy (MESORTIBO)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pleural Mesothelioma Malignant
Lead sponsor: Centro di Riferimento Oncologico - Aviano
Sponsor class: OTHER
First posted: 2024-10-15
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: up to 36 months
Secondary outcomes:
measure: Relation between the severity of radio-induced toxicity and trend of biomarkers associated with it
timeFrame: up to 36 months
measure: Identifying biomarkers associated with lung toxicity potentially predictive of pulmonary fibrosis
timeFrame: up to 36 months
measure: Identifying signs of radio-induced immunomodulation among significant changes induced by hemithoracic radical radiotherapy in analysed biomarkers
timeFrame: up to 36 months
measure: Association between the levels of biomarkers measured at the end of treatment radiation and overall survival (OS) at 24 months
timeFrame: 24 moths after end of treatment
measure: To assess the prognostic potential of basal levels of analysed biomarkers
timeFrame: up to 36 months
measure: Association between the levels of biomarkers variation (between baseline and treatment end) and Progression Free Survival (PFS) at 12 months
timeFrame: 12 months after end of treatment
Other outcomes:
Locations:
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS
state: Pordenone
Study officials:
affiliation: Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS
name: Alberto Revelant, MD
role: PRINCIPAL_INVESTIGATOR
References: