A phase III randomized trial of pleurectomy/decortication plus chemotherapy with or without adjuvant hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) for malignant pleural mesothelioma (MPM) (NRG LU-006).

Abstract

TPS9079 Background: Pleurectomy/Decortication (P/D) with neoadjuvant or adjuvant chemotherapy has become a common lung-sparing surgical approach for MPM. Adjuvant hemithoracic IMPRINT was developed at Memorial Sloan Kettering Cancer Center and safe in a multi-institutional phase II study, with promising survival outcomes. The National Cancer Institute (NCI) sponsored this phase III randomized cooperative group trial to test the efficacy of this lung-sparing trimodality approach for resectable MPM. Methods: Patients with newly diagnosed MPM amenable to P/D are enrolled and undergo P/D followed by adjuvant platinum/pemetrexed (preferred) or neoadjuvant chemotherapy followed by P/D. Patients are stratified by histologic subtype, resection status (R0/1 vs. R2), and center patient volume (≤10 vs. > 10 P/Ds per year). Within 8 weeks after completion of the second modality patients are randomized 1:1 to undergo hemithoracic IMPRINT vs. no further therapy. All IMPRINT contours and treatment plans will be centrally reviewed. A contouring atlas and treatment planning constraints for target structures and organs at risk including acceptable and unacceptable variations and deviations were developed. Photon and proton therapy are permitted. The primary endpoint of the study is overall survival. Secondary endpoints include local failure-free, distant-metastases-free and progression-free survival, treatment-related toxicities (CTCAE v5.0) and change in quality-of-life (EORTC QLQ-C30 mean score changes at 9 months post randomization). The target accrual is 150 patients. This study was activated on January 29, 2020. Over 20 institutions have already committed to opening the study which is open to all National Clinical Trials Network (NCTN) sites. Treatment planning guidelines and helpful hints for photon and proton therapy will be presented. Conclusions: NRG LU-006 (clinicaltrials.gov: NCT04158141 ) is open to accrual. This is the first NRG Oncology randomized phase III trial on MPM and evaluates the use of IMPRINT following lung-sparing P/D and chemotherapy. This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC) from the National Cancer Institute (NCI). Clinical trial information: NCT04158141.