IMPALA

Phase 1

• Conditions: 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; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003003-35-FR
• Lead Sponsor: CHU de LILLE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-03-03
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

Patients (male or female) =18 years old (n=20)
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 (Nowak and Armato, J Thorac Oncol 2018)
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)
No contraindications to 5-ALA, PDT or Nivolumab
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 )
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

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
Usual contra-indications for anti-PD-1 antibodies (Nivolumab) 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 clairance <60 ml/min), uncontroled 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective of this study is to demonstrate the feasibility of the innovative therapeutic strategy combining intrapleural PDT by VATS then immunotherapy by Nivolumab in MPM patients without inacceptable and unexpected toxicity.;Secondary Objective: (a) to describe patients outcome<br>(b) to assess the impact of experimental treatment on quality of life and chest pain;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: At the end of the treatment for each patient

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): (a)objective response rate (ORR), progression free survival (PFS), and overall survival (OS);<br>(b)score Meso LCSS-30, and EVA scale;Timepoint(s) of evaluation of this end point: (a) at the end of the study (LVLS)<br>(b) throughout the study (screening, treatment, end of treatment)