RecruitingPhase 2NCT04400539

The IMmunotherapy Pleural 5-ALA PDT

Intrapleural Photodynamic Therapy by Video-Assisted Thoracoscopy Followed by Anti-PD-1 NIVOLUMAB in Patients With Malignant Pleural Mesothelioma - a Pilot Study

Sponsor

University Hospital, Lille

Enrollment

20 participants

Start Date

May 9, 2022

Study Type

INTERVENTIONAL

Conditions

Malignant Pleural Mesothelioma Mesotheliomas Pleural

Summary

Pilot study of the feasibility of an innovative multimodal treatment combining intrapleural photodynamic therapy with videothoracoscopy followed by adjuvant immunotherapy with anti-PD-1 Nivolumab antibodies in patients with malignant pleural mesothelioma

Eligibility

Min Age: 18 Years

Inclusion Criteria15

ECOG Performance status (PS) 0-1 (WHO)
Unresectable Malignant Pleural Mesothelioma
suffering from unresectable MPM (n=20), relapsing after one or 2 lines of treatment with platinum-based doublet of chemotherapy (including pemetrexed) \[Note: MPM patients having contra-indications for, or refusing chemotherapy may also be recruited\], and candidate for palliative pleural procedure (i.e. thoracoscopy for pleurodesis by talc or by insertion of indwelled pleural catheter, IPC)
Documented progression after previous 1 or 2 lines of chemotherapy including Platinum/Pemetrexed chemotherapy\*
Measurable disease according to modified RECIST 1.1. for MPM
Malignant pleural lesion assessed to be accessible by local PDT treatment during thoracoscopy, as validated by expert MTB ("MESOCLIN", Lille, France)
Histological diagnosis confirmed by national expert pathology panel ("MESOPATH" - Institut Léon Bérard, Lyon, France)
Weight loss \<10%
available tumor tissue (archival or fresh)
obtention of an informed written consent before any specific procedure of the study
Decision to treat the patient within this clinical trial taken during MPM dedicated multidisciplinary board (RCP MESOCLIN in France )
Patient affiliated to and covered by social security for standard care
Women of child-bearing potential must use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and must agree to continue using such precautions for 5 months after the final dose of investigational product
Women of child-bearing potential must have a negative pregnancy test within 24h before administration of investigational product
First line patients may also be recruited if they declined or if they have contra-indications for chemotherapy.

Exclusion Criteria13

lack of informed written consent; or refusal to sign or to participate
Pregnant, breastfeeding patients, and female patients of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in the protocol for the duration of the study and for at least 5 months after the last dose of nivolumab
Male patients who are unwilling or unable to use contraception methods for the duration of the study and for at least 7 months after the last dose of nivolumab
a previous treatment by anti-PD-1 or anti-PD-L1 antibodies for their cancer or any other cancer in the last 5 years
hypersensitivity to Nivolumab (anti-PD-1 antibodies)
contra-indications for 5-ALA or PDT
contra-indications for thoracoscopy (VATS)
any other comorbidity precluding the feasibility of the therapeutic protocol: uncontrolled cardiac failure, pulmonary hypertension, liver or kidney severe dysfunction (creatinin clearance \<60 ml/min), uncontrolled infection, or other disease according to the investigator
other cancer treated within 5 years before inclusion except baso-cellular skin carcinoma or cervical / bladder in situ carcinoma
inability to receive study information and to give informed consent
patient unable to have a clinical follow-up due to psychological, familial, social or geographical reasons
legal incapacity (people in jail), or under supervision (i.e. guardianship or curatorship)
treatment with experimental drug within 30 days before the start of the study

Interventions

DEVICEintrapleural photodynamic therapy with videothoracoscopy

MPM patients will be first administrated 20 mg/kg of oral photosensitizer, 5-Aminolevulinic Acid (5-ALA) {Gliolan®}, 4 to 6 hours prior undergoing thoracoscopy (VATS). During VATS procedure, after a qualitative control of the fluorescence of tumor lesions and some guided pleural tumor biopsies, the pleural cavity will be illuminated using a flexible probe and laser source at a specific wavelength for 5-ALA (400-500 nm; 25 J/cm2) during 15 minutes (6 fractions of 2.5 minutes separated by 5 pauses of 2 minutes each to improve tissue oxygenation for the PDT reaction). An IPC device (but no talc) will be inserted and used for pleurodesis and may permit to collect further pleural effusion samples. As 5-ALA has a short half-life and thus does not need extensive precautions to avoid patient photosensitivity, the patient would not stay longer than a standard procedure (about 2-3 days in the hospital)

DRUGNivolumab Injection

Seven to 10 days after VATS, patients will start to be treated by Nivolumab 240mg IV every 2 weeks till progression (CT-scan reassessment every 8 cycles), unacceptable toxicity, or maximum 2 years.