The IMmunotherapy Pleural 5-ALA PDT (IMPALA)

January 5, 2023 updated by: University Hospital, Lille

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Lille, France, 59037
        • Recruiting
        • Institut Coeur-Poumon, CHU

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Malignant Pleural Mesothelioma patients
Device: intrapleural photodynamic therapy with videothoracoscopy
MPM patients will be first administrated 20 mg/kg of oral photosensitizer, 5-Aminolevulinic Acid (5-ALA) {Gliolan®}, 4 to 6 hours prior undergoing thoracoscopy (VATS). During VATS procedure, after a qualitative control of the fluorescence of tumor lesions and some guided pleural tumor biopsies, the pleural cavity will be illuminated using a flexible probe and laser source at a specific wavelength for 5-ALA (400-500 nm; 25 J/cm2) during 15 minutes (6 fractions of 2.5 minutes separated by 5 pauses of 2 minutes each to improve tissue oxygenation for the PDT reaction). An IPC device (but no talc) will be inserted and used for pleurodesis and may permit to collect further pleural effusion samples. As 5-ALA has a short half-life and thus does not need extensive precautions to avoid patient photosensitivity, the patient would not stay longer than a standard procedure (about 2-3 days in the hospital)
Drug: Nivolumab Injection
Seven to 10 days after VATS, patients will start to be treated by Nivolumab 240mg IV every 2 weeks till progression (CT-scan reassessment every 8 cycles), unacceptable toxicity, or maximum 2 years.
Other Names:
  • adjuvant immunotherapy with anti-PD-1 Nivolumab antibodies

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the proportion of patients having the full multimodal treatment
Time Frame: through study completion, an average of 24 months
the proportion of patients having the full multimodal treatment (target: 70% minimum of total patients,14 out of 20 patients) without inacceptable and unexpected toxicity (grade≥3) according National Cancer Institute (NCI) criteria, reviewed by an Independent Survey Committee.
through study completion, an average of 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
objective response rate (ORR) according to modified RECIST 1.1 criteria for mesothelioma for pleural lesions; RECIST 1.1 for all other targets
Time Frame: through study completion, an average of 24 months
through study completion, an average of 24 months
Kaplan Meier curve for overall survival (mOS)
Time Frame: through study completion, an average of 24 months
through study completion, an average of 24 months
Kaplan Meier curve for progression free survival (mPFS)
Time Frame: through study completion, an average of 24 months
through study completion, an average of 24 months
quality of life (QoL) of patients by dedicated EORTC QLQ C30 (or LCSS-30) questionnaire
Time Frame: At baseline and
The Quality of life questionnaire (QLQ-C30) contains 29 items dealing with fatigue, pain, nausea and vomiting, general condition and social, emotional and cognitive functions. It is currently used in many clinical trials in oncology
At baseline and
evaluation of chest pain using visual scale.
Time Frame: through study completion, an average of 24 months
through study completion, an average of 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Lille

Collaborators

INSERM U1189 ONCOTHAI

Investigators

  • Principal Investigator: Arnaud Scherpereel, MD,PhD, University Hospital, Lille

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 9, 2022

Primary Completion (Anticipated)

May 1, 2026

Study Completion (Anticipated)

May 1, 2026

Study Registration Dates

First Submitted

May 20, 2020

First Submitted That Met QC Criteria

May 20, 2020

First Posted (Actual)

May 22, 2020

Study Record Updates

Last Update Posted (Estimate)

January 9, 2023

Last Update Submitted That Met QC Criteria

January 5, 2023

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019_41
  • 2019-003003-35 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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