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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Lille

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 May 2022 → ongoing

Decision date (initial)

2024-09-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Grants from the European Respiratory Society (ERS), and from La Ligue contre le Cancer (France) · Pulmonary&Thoracic Oncology Department, CHULille (Unit UF 9586), “Fonds de Dotation CHU lille" · INSERM ONCOTHAI (U1189), Bâtiment ONCOLILLE, Boulevard du Pr. Jules Leclercq, 59000 Lille · Bristol-Myers Squibb (BMS) [research funding stopped on December 2020 due to BMS decision in the COV

External identifiers

EU CT number

2024-514103-33-00

EudraCT number

2019-003003-35

ClinicalTrials.gov

NCT04400539

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

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 objectives 3

1. to describe patients outcome using following data: objective response rate (ORR), progression free survival (PFS), and overall survival (OS)
2. to assess the impact of experimental treatment on quality of life (QoL) and chest pain by a kinetic assessment of these parameters by the lung cancer symptom score Meso LCSS-30, and EVA scale, respectively.
3. Ancillary/biomarkers studies: (a) on (archived and/or fresh, i.e. pleural biopsies just before PDT) tumor tissues at baseline ± 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; (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 ; (c) pleural effusion samples will be collected on EDTA during VATS then through IPC in the same goal than (b). Note: patients will sign a specific informed consent for these studies

Conditions and MedDRA coding

malignant pleural mesothelioma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Patients (male or female) ≥18 years old (n=20)
2. ECOG Performance status (PS) 0-1 (WHO)
3. Unresectable Malignant Pleural Mesothelioma
4. 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)
5. 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.
6. Patient eligible for Nivolumab as validated by expert MTB (“NETMESO/MESOCLIN” French network, Lille, France), and in accordance with RTU procedure for drug access
7. Measurable disease according to modified RECIST 1.1. for MPM (Nowak and Armato, J Thorac Oncol 2018)
8. Malignant pleural lesion assessed to be accessible by local PDT treatment during thoracoscopy, as validated by expert MTB (“NETMESO/MESOCLIN” French network, Lille, France)
9. Histological diagnosis confirmed by local and/or national (Institut Léon Bérard, Lyon, France) expert pathology panel of the “NETMESO/MESOPATH” French network
10. Weight loss <10%
11. Available tumor tissue (archival or fresh)
12. No contraindications to 5-ALA, PDT or Nivolumab
13. Obtention of an informed written consent before any specific procedure of the study
14. Decision to treat the patient within this clinical trial taken during MPM dedicated multidisciplinary board (RCP NETMESO/ MESOCLIN in France )
15. Patient affiliated to and covered by social security for standard care
16. 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
17. Women of child-bearing potential must have a negative pregnancy test within 24h before administration of investigational product

Exclusion criteria 12

1. Lack of informed written consent; or refusal to sign or to participate
2. 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
3. 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
4. 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.
5. Usual contra-indications for anti-PD-1 antibodies (Nivolumab) or PDT
6. Contra-indications for thoracoscopy (VATS)
7. 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
8. Other cancer treated within 5 years before inclusion except baso-cellular skin carcinoma or cervical / bladder in situ carcinoma
9. Inability to receive study information and to give informed consent
10. Patient unable to have a clinical follow-up due to psychological, familial, social or geographical reasons
11. Legal incapacity (people in jail), or under supervision (i.e. guardianship or curatorship)
12. Treatment with experimental drug within 30 days before the start of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 8

1. 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
2. Kaplan Meier curve for overall survival (mOS)
3. Kaplan Meier curve for progression free survival (mPFS)
4. assessment of quality of life (QoL) of patients by dedicated EORTC QLQ C30 (or LCSS-30) questionnaire before and after treatment (in annex
5. evaluation of chest pain evaluation using visual scale.
6. 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;
7. 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 ;
8. 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).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Lille

Sponsor organisation

Centre Hospitalier Universitaire De Lille

Address

2 Avenue Oscar Lambret, Cs 70001 Cs 70001

City

Lille Cedex

Postcode

59037

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Lille

Contact name

Pr Arnaud SCHERPEREEL

Public contact point

Organisation

Centre Hospitalier Universitaire De Lille

Contact name

Pr Arnaud SCHERPEREEL

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications