Aminolevulinic acid hydrochloride for Malignant pleural mesothelioma

Inclusion criteria

• {"criterion_text":"- Patients (male or female) ≥18 years old (n=20)"}
• {"criterion_text":"- Weight loss <10%"}
• {"criterion_text":"- Available tumor tissue (archival or fresh)"}
• {"criterion_text":"- No contraindications to 5-ALA, PDT or Nivolumab"}
• {"criterion_text":"- Obtention of an informed written consent before any specific procedure of the study"}
• {"criterion_text":"- Decision to treat the patient within this clinical trial taken during MPM dedicated multidisciplinary board (RCP NETMESO/ MESOCLIN in France )"}
• {"criterion_text":"- Patient affiliated to and covered by social security for standard care"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Women of child-bearing potential must have a negative pregnancy test within 24h before administration of investigational product"}
• {"criterion_text":"- ECOG Performance status (PS) 0-1 (WHO)"}
• {"criterion_text":"- Unresectable Malignant Pleural Mesothelioma"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Documented progression after previous 1 or 2 lines of chemotherapy including Platinum/Pemetrexed chemotherapy* *First line patients may also be recruited if they declined or if they have contra-indications for chemotherapy."}
• {"criterion_text":"- Patient eligible for Nivolumab as validated by expert MTB (“NETMESO/MESOCLIN” French network, Lille, France), and in accordance with RTU procedure for drug access"}
• {"criterion_text":"- Measurable disease according to modified RECIST 1.1. for MPM (Nowak and Armato, J Thorac Oncol 2018)"}
• {"criterion_text":"- Malignant pleural lesion assessed to be accessible by local PDT treatment during thoracoscopy, as validated by expert MTB (“NETMESO/MESOCLIN” French network, Lille, France)"}
• {"criterion_text":"- Histological diagnosis confirmed by local and/or national (Institut Léon Bérard, Lyon, France) expert pathology panel of the “NETMESO/MESOPATH” French network"}

Exclusion criteria

• {"criterion_text":"- Lack of informed written consent; or refusal to sign or to participate"}
• {"criterion_text":"- Patient unable to have a clinical follow-up due to psychological, familial, social or geographical reasons"}
• {"criterion_text":"- Legal incapacity (people in jail), or under supervision (i.e. guardianship or curatorship)"}
• {"criterion_text":"- Treatment with experimental drug within 30 days before the start of the study"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- A previous treatment by anti-PD-1 or anti-PD-L1 antibodies for their cancer or any other cancer in the last 5 years, with the exception of the Nivolumab + Ipilimumab combination, or (platinum/pemetrexed) + immunotherapy as alternative first line treatments in pleural mesothelioma."}
• {"criterion_text":"- Usual contra-indications for anti-PD-1 antibodies (Nivolumab) or PDT"}
• {"criterion_text":"- Contra-indications for thoracoscopy (VATS)"}
• {"criterion_text":"- Any other comorbidity precluding the feasibility of the therapeutic protocol: uncontrolled cardiac failure, pulmonary hypertension, liver or kidney severe dysfunction (creatinin clairance <60 ml/min), uncontroled infection, or other disease according to the investigator"}
• {"criterion_text":"- Other cancer treated within 5 years before inclusion except baso-cellular skin carcinoma or cervical / bladder in situ carcinoma"}
• {"criterion_text":"- Inability to receive study information and to give informed consent"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint will be the proportion of patients having the full multimodal treatment (target: 70% 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 Committee.","definition_or_measurement_approach":"Proportion of patients completing full multimodal treatment without inacceptable/unexpected toxicity (grade ≥3) assessed using NCI criteria; target threshold is ≥70% (14/20); events reviewed by an Independent Survey Committee."}

Secondary endpoints

• {"endpoint_text":"- objective response rate (ORR) according to modified RECIST 1.1 criteria for mesothelioma (Armato and Nowak, J Thorac Oncology 2018) for pleural lesions; RECIST 1.1 for all other targets","definition_or_measurement_approach":"ORR assessed by modified RECIST 1.1 for mesothelioma for pleural lesions (Armato and Nowak) and RECIST 1.1 for other targets."}
• {"endpoint_text":"- Kaplan Meier curve for overall survival (mOS)","definition_or_measurement_approach":"Overall survival estimated using Kaplan-Meier analysis."}
• {"endpoint_text":"- Kaplan Meier curve for progression free survival (mPFS)","definition_or_measurement_approach":"Progression-free survival estimated using Kaplan-Meier analysis."}
• {"endpoint_text":"- assessment of quality of life (QoL) of patients by dedicated EORTC QLQ C30 (or LCSS-30) questionnaire before and after treatment (in annex","definition_or_measurement_approach":"Quality of life measured using EORTC QLQ-C30 or LCSS-30 questionnaires administered before and after treatment."}
• {"endpoint_text":"- evaluation of chest pain evaluation using visual scale.","definition_or_measurement_approach":"Chest pain intensity measured by visual analogue scale (EVA)."}
• {"endpoint_text":"- Ancillary/biomarkers studies: (a) on fresh pleural tumor biopsies (done during VATS and PDT procedure) compared with tumor tissue obtained at the time of MPM diagnosis ± at the time of progression (if available): by immunohistochemistry (BAP-1, PD-L1… expression), whole exome sequencing (WES) including tumor mutational burden (TMB) and search of tumor specific variants in ctDNA, immune cells populations, etc;","definition_or_measurement_approach":"Biomarker analyses on fresh pleural biopsies vs archival tissue: immunohistochemistry (BAP-1, PD-L1), WES including TMB, ctDNA variant analysis, immune cell population profiling."}
• {"endpoint_text":"- Ancillary/biomarkers studies: (b) blood (plasma) samples will be collected before PDT, during Nivolumab treatment and at the time of progression enabling a monitoring of ctDNA and of biomarkers reflecting the anti-tumor immune response ;","definition_or_measurement_approach":"Serial plasma collection pre-PDT, during nivolumab, and at progression for ctDNA monitoring and immune-response biomarkers."}
• {"endpoint_text":"- Ancillary/biomarkers studies: (c) pleural effusion samples (when accessible) will be collected on EDTA during VATS then through IPC in the same goal than (b).","definition_or_measurement_approach":"Pleural effusion collection (EDTA) during VATS and via IPC when accessible for ctDNA and immune-response biomarker analyses."}

France

Earliest CTIS Part Ii Submission Date

13-09-2024

Latest Decision Or Authorization Date

12-05-2026

Processing Time Days

606

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Lille

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France