Innovative treatment combining photodynamic therapy and immunotherapy for malignant pleural mesothelioma

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

This study is testing a new treatment that combines light therapy and immune therapy to see if it can help patients with advanced malignant pleural mesothelioma who haven't responded well to chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Lille (Academic / other)
• Drugs / interventions: nivolumab, chemotherapy, immunotherapy
• Locations: 1 site (Lille)
• Trial ID: NCT04400539 on ClinicalTrials.gov

What this trial studies

This pilot study investigates the feasibility of a novel multimodal treatment approach for patients with unresectable malignant pleural mesothelioma. It combines intrapleural photodynamic therapy using videothoracoscopy with adjuvant immunotherapy using Nivolumab, an anti-PD-1 antibody. The study aims to assess the effectiveness of this combination in patients who have previously undergone chemotherapy and are experiencing disease progression. The treatment is designed to target malignant pleural lesions directly while enhancing the immune response against the cancer.

Who should consider this trial

Good fit: Ideal candidates include patients with unresectable malignant pleural mesothelioma who have experienced disease progression after one or two lines of chemotherapy.

Not a fit: Patients with resectable mesothelioma or those who are not candidates for palliative pleural procedures may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced malignant pleural mesothelioma who have limited treatment choices.

How similar studies have performed: While this approach is innovative, similar multimodal treatments combining photodynamic therapy and immunotherapy have shown promise in other studies, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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

Where this trial is running

Lille

• Institut Coeur-Poumon, CHU — Lille, France (Recruiting)

Study contacts

• Principal investigator: Arnaud Scherpereel, MD,PhD — University Hospital, Lille
• Study coordinator: Arnaud Scherpereel, MD,PhD

Conditions Mesotheliomas Pleural; Malignant Pleural Mesothelioma; Immunotherapy; anti-PD-1; Photodynamic Therapy