Induction Chemo+Immunotherapy in Resectable Epithelioid and Biphasic Pleural Mesothelioma (CHIMERA Study) — CHIMERA  

Pleural Mesothelioma Clinical Trial

Official title: Phase II Study of Pembrolizumab in Combination With Cisplatin or Carboplatin and Pemetrexed as Induction Chemo+Immunotherapy in Resectable Epithelioid and Biphasic Pleural Mesothelioma (CHIMERA Study)

Status Not yet recruiting

Clinical Trial Summary

This is a prospective, open-label, multi-site Phase II trial of pembrolizumab in combination with pemetrexed and cisplatin or carboplatin as neo-adjuvant therapy followed by surgery and adjuvant pembrolizumab in patients affected by resectable stage I-IIIa chemonaïve epithelioid/biphasic pleural mesothelioma.

Clinical Trial Description

This is a prospective, open-label, multi-site Phase II trial of pembrolizumab in combination with pemetrexed and cisplatin or carboplatin as neo-adjuvant therapy followed by surgery and adjuvant pembrolizumab in patients affected by resectable stage I-IIIa chemonaïve epithelioid/biphasic pleural mesothelioma.

The neoadjuvant systemic treatment will be based on three cycles of pembrolizumab 200 mg flat dose in combination with standard doses of cisplatin (75 mg/sm) or carboplatin (AUC 5) and pemetrexed (500 mg/sm) administered intra-venous every 3 weeks.

The surgical intervention of pleurectomy/decortication will be planned to occur within 6 weeks after the completion of neoadjuvant treatment.

The adjuvant systemic treatment will be based on 14 cycles of pembrolizumab 200 mg flat dose administered intra-venous every 3 weeks. Patients should be able to start pembrolizumab following surgery as soon as clinically feasible and within 10 weeks from surgery.

All participating centers will enroll eligible patients and administer neoadjuvant and adjuvant systemic treatment.

Thoracic surgery will be centralized in two reference centres (AOUPD PADOVA AND HUMANITAS CANCER CENTER).

All eligible patients will undergo two multidisciplinary team discussions, before and after induction systemic treatment.

The primary objective of this trial is to determine the pathological complete response rate of pembrolizumab in combination with standard doses of cisplatin or carboplatin and pemetrexed administered intra-venous every 3 weeks for three cycles. Pathological response will be centrally assessed by a blinded pathologist.

Radiological and metabolic assessment through CT-scan and PET-CT will be performed at the baseline and at the end of neoadjuvant chemo-immunotherapy. Radiological CT-scan will be then performed every 9 weeks (+/- 1 week) during the adjuvant treatment. Further radiological follow-up after the end of study treatment (or for those patients with early treatment discontinuation without disease relapse) will be performed every 12 weeks until a two-year period from surgery, followed by every 18 weeks until the fifth year.

Radiological response will be centrally assessed by a blinded radiologist. Adverse events will be monitored throughout the trial and graded in severity according to the guidelines outlined in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. ;

Related Conditions & MeSH terms

• Mesothelioma
• Mesothelioma, Malignant
• Pleural Mesothelioma

• NCT number: NCT06155279
• Study type: Interventional
• Source: Istituto Oncologico Veneto IRCCS
• Contact: Giulia Pasello, MD
• Phone: 0498215931
• Email: giulia.pasello@iov.veneto.it
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2024
• Completion date: December 2026