The IMmunotherapy Pleural 5-ALA PDT “IMPALA” trial project: Pilot study of the feasibility of an innovative multimodal treatment combining intrapleural photodynamic therapy controlled by videothoracoscopy followed by adjuvant immunotherapy with anti-PD-1 Nivolumab antibody in patients with malignant pleural mesothelioma
Ongoing / closed: Ongoing
CPP sud-Est II approval : 18 may 2020
ANSM approval : 15 may 2020
Research type (retro/prospective): Academic, pilot, feasibility, phase 2, one-arm, monocentric study
Summary: Malignant pleural mesothelioma is a rare, aggressive cancer that develops in the pleura, a thin layer of tissue surrounding the lungs. Malignant pleural mesothelioma (MPM) is associated with a poor prognosis, with a median survival from 13 to 19 months for patients not eligible for a radical surgery. Pleural biopsies by thoracoscopy (VATS) are the gold standard to obtain a firm histological diagnosis of MPM, and may also help for tumor staging and palliative treatment (i.e. talc pleurodesis and/or insertion of indwelled pleural catheter, IPC).
Immunotherapy such as anti-PD-1 antibodies appears these last years as a major therapeutic tool for many cancers including recently, fMPM (Lancet Oncol 2018, IFCT MAPS-2 trial, NivoMes trial…). Photodynamic therapy (PDT), a widely used therapeutic modality, is also a promising anti-tumor because the reaction of a drug photosensitizer administrated to patient (IV, oral or local administration), in combination with oxygen, when exposed to light (at specific wavelength) may locally induce toxic radicals, killing specifically malignant cells. Moreover, the immunogenic cell death induced by PDT could later favor anti-tumor immune response.
Our research lab ONCOTHAI is highly experienced in lasers and PDT for many years, managing several PDT-based clinical trials with the University Hospital (CHU) of Lille in prostate cancer, glioma, skin cancers and diseases, malignant pleural mesothelioma (MesoPDT, based on previous promising US results from Friedberg J et al)
Photosensitizers such as 5-Aminolevulinic Acid (5-ALA; Gliolan®) were also already used in pleural malignancies for diagnostic purpose during VATS because of its specific uptake by tumor cells that may help to better visualize these cells (becoming fluorescent with specific light exposure).
àThese advantages of both immunotherapy and PDT led us to propose a combination of the two treatments to improve local anti-tumor effect in pleural malignancies but also to enhance distant action of anti-PD-1 drug (Nivolumab) in the case of MPM. Based on a rationale of a synergistic effect of PDT and checkpoint inhibitors we hope to induce a strong anti-tumor immune response without cumulative toxicity, leading to a better outcome for these patients compared to anti-PD-1 treatment alone.
Principal Investigator: Pr Arnaud SCHERPEREEL
Scientific coordinator: Pr Serge MORDON U1189 Inserm
Study Sponsor: CHU of Lille
Primary endpoints: feasibility of the full strategy without unexpected side effects compared to Nivolumab alone (none are expected, induced by 5-ALA)
Secondary endpoints will include quality of life (scales), chest pain assessment (EVA scale), cost evaluation, but also objective response rate, progression free survival, overall survival data to be compared with previous Nivolumab trials and historical series (ASCO, ESMO, WCLC 2017…). Ancillary studies (PD-L1, TMB, immune cells populations…) will assess at baseline (pleural biopsies…) and during treatment with a study of kinetics of the anti-tumor immune response on blood and pleural effusion samples (collected through IPC) +/- optional new pleural biopsies with patients specific consent.
Evaluation criteria of the primary endpoint: The main criterion will be the proportion of patients having the full multimodal treatment (target: 66% minimum of total patients, i.e. 14 out of 20 patients) without inacceptable and unexpected toxicity (grade≥3) according National Cancer Institute (NCI) criteria, reviewed by an Independent Survey Commity.
Evaluation criteria of the secondary endpoints:
- Objective response rate (ORR)
- median overall survival (mOS)
- median progression free survival (mPFS)
- assessment of quality of life (QoL) of patients by dedicated EORTC QLQ C30 (or LCSS-30) questionnaire before and after treatment
- evaluation of chest pain evaluation using visual scale.
Estimated enrollment: 25 MPM patients.
Clinicaltrials.gov identifier: NCT04400539
Contact and location:
Professeur Arnaud SCHERPEREEL
Adresse : Pneumologie et Oncologie Thoracique, Hôpital Calmette, CHRU de Lille
Phone : +33 (0)3 20 44 49 98
Unité Inserm U1189 ONCOTHAI, 1 avenue Oscar Lambret, 59037 LILLE CEDEX
Phone: +33 (0)3 20 44 67 09