Clinical trial NCT04400539: The IMmunotherapy Pleural 5-ALA PDT
Official title: Intrapleural Photodynamic Therapy by Video-Assisted Thoracoscopy Followed by Anti-PD-1 NIVOLUMAB in Patients With Malignant Pleural Mesothelioma - a Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Mesotheliomas Pleural
Malignant Pleural Mesothelioma
Keywords: Immunotherapy
anti-PD-1
Photodynamic Therapy
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: INSERM U1189 ONCOTHAI
First posted: 2020-05-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 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

Primary outcomes:
measure: the proportion of patients having the full multimodal treatment
timeFrame: through study completion, an average of 24 months
Secondary outcomes:
measure: objective response rate (ORR) according to modified RECIST 1.1 criteria for mesothelioma for pleural lesions; RECIST 1.1 for all other targets
timeFrame: through study completion, an average of 24 months
measure: Kaplan Meier curve for overall survival (mOS)
timeFrame: through study completion, an average of 24 months
measure: Kaplan Meier curve for progression free survival (mPFS)
timeFrame: through study completion, an average of 24 months
measure: quality of life (QoL) of patients by dedicated EORTC QLQ C30 (or LCSS-30) questionnaire
timeFrame: At baseline and
measure: evaluation of chest pain using visual scale.
timeFrame: through study completion, an average of 24 months
Other outcomes:
Locations:
city: Lille
country: France
facility: Institut Coeur-Poumon, CHU
Study officials:
affiliation: University Hospital, Lille
name: Arnaud Scherpereel, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: