<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04400539</url>
  </required_header>
  <id_info>
    <org_study_id>2019_41</org_study_id>
    <secondary_id>2019-003003-35</secondary_id>
    <nct_id>NCT04400539</nct_id>
  </id_info>
  <brief_title>The IMmunotherapy Pleural 5-ALA PDT</brief_title>
  <acronym>IMPALA</acronym>
  <official_title>Intrapleural Photodynamic Therapy by Video-Assisted Thoracoscopy Followed by Anti-PD-1 NIVOLUMAB in Patients With Malignant Pleural Mesothelioma - a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>INSERM U1189 ONCOTHAI</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Lille</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pilot study of the feasibility of an innovative multimodal treatment combining intrapleural&#xD;
      photodynamic therapy with videothoracoscopy followed by adjuvant immunotherapy with anti-PD-1&#xD;
      Nivolumab antibodies in patients with malignant pleural mesothelioma&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 9, 2022</start_date>
  <completion_date type="Anticipated">May 2026</completion_date>
  <primary_completion_date type="Anticipated">May 2026</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the proportion of patients having the full multimodal treatment</measure>
    <time_frame>through study completion, an average of 24 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>objective response rate (ORR) according to modified RECIST 1.1 criteria for mesothelioma for pleural lesions; RECIST 1.1 for all other targets</measure>
    <time_frame>through study completion, an average of 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kaplan Meier curve for overall survival (mOS)</measure>
    <time_frame>through study completion, an average of 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kaplan Meier curve for progression free survival (mPFS)</measure>
    <time_frame>through study completion, an average of 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>quality of life (QoL) of patients by dedicated EORTC QLQ C30 (or LCSS-30) questionnaire</measure>
    <time_frame>At baseline and</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>evaluation of chest pain using visual scale.</measure>
    <time_frame>through study completion, an average of 24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Mesotheliomas Pleural</condition>
  <condition>Malignant Pleural Mesothelioma</condition>
  <arm_group>
    <arm_group_label>Malignant Pleural Mesothelioma patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>intrapleural photodynamic therapy with videothoracoscopy</intervention_name>
    <description>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)</description>
    <arm_group_label>Malignant Pleural Mesothelioma patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab Injection</intervention_name>
    <description>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.</description>
    <arm_group_label>Malignant Pleural Mesothelioma patients</arm_group_label>
    <other_name>adjuvant immunotherapy with anti-PD-1 Nivolumab antibodies</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ECOG Performance status (PS) 0-1 (WHO)&#xD;
&#xD;
          -  Unresectable Malignant Pleural Mesothelioma&#xD;
&#xD;
          -  suffering from unresectable MPM (n=20), relapsing after one or 2 lines of treatment&#xD;
             with platinum-based doublet of chemotherapy (including pemetrexed) [Note: MPM patients&#xD;
             having contra-indications for, or refusing chemotherapy may also be recruited], and&#xD;
             candidate for palliative pleural procedure (i.e. thoracoscopy for pleurodesis by talc&#xD;
             or by insertion of indwelled pleural catheter, IPC)&#xD;
&#xD;
          -  Documented progression after previous 1 or 2 lines of chemotherapy including&#xD;
             Platinum/Pemetrexed chemotherapy*&#xD;
&#xD;
          -  Measurable disease according to modified RECIST 1.1. for MPM&#xD;
&#xD;
          -  Malignant pleural lesion assessed to be accessible by local PDT treatment during&#xD;
             thoracoscopy, as validated by expert MTB (&quot;MESOCLIN&quot;, Lille, France)&#xD;
&#xD;
          -  Histological diagnosis confirmed by national expert pathology panel (&quot;MESOPATH&quot; -&#xD;
             Institut Léon Bérard, Lyon, France)&#xD;
&#xD;
          -  Weight loss &lt;10%&#xD;
&#xD;
          -  available tumor tissue (archival or fresh)&#xD;
&#xD;
          -  obtention of an informed written consent before any specific procedure of the study&#xD;
&#xD;
          -  Decision to treat the patient within this clinical trial taken during MPM dedicated&#xD;
             multidisciplinary board (RCP MESOCLIN in France )&#xD;
&#xD;
          -  Patient affiliated to and covered by social security for standard care&#xD;
&#xD;
          -  Women of child-bearing potential must use a highly effective method of contraception&#xD;
             for 28 days prior to the first dose of investigational product, and must agree to&#xD;
             continue using such precautions for 5 months after the final dose of investigational&#xD;
             product&#xD;
&#xD;
          -  Women of child-bearing potential must have a negative pregnancy test within 24h before&#xD;
             administration of investigational product&#xD;
&#xD;
          -  First line patients may also be recruited if they declined or if they have&#xD;
             contra-indications for chemotherapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  lack of informed written consent; or refusal to sign or to participate&#xD;
&#xD;
          -  Pregnant, breastfeeding patients, and female patients of childbearing potential who&#xD;
             are unwilling or unable to use a highly effective method of contraception as outlined&#xD;
             in the protocol for the duration of the study and for at least 5 months after the last&#xD;
             dose of nivolumab&#xD;
&#xD;
          -  Male patients who are unwilling or unable to use contraception methods for the&#xD;
             duration of the study and for at least 7 months after the last dose of nivolumab&#xD;
&#xD;
          -  a previous treatment by anti-PD-1 or anti-PD-L1 antibodies for their cancer or any&#xD;
             other cancer in the last 5 years&#xD;
&#xD;
          -  hypersensitivity to Nivolumab (anti-PD-1 antibodies)&#xD;
&#xD;
          -  contra-indications for 5-ALA or PDT&#xD;
&#xD;
          -  contra-indications for thoracoscopy (VATS)&#xD;
&#xD;
          -  any other comorbidity precluding the feasibility of the therapeutic protocol:&#xD;
             uncontrolled cardiac failure, pulmonary hypertension, liver or kidney severe&#xD;
             dysfunction (creatinin clearance &lt;60 ml/min), uncontrolled infection, or other disease&#xD;
             according to the investigator&#xD;
&#xD;
          -  other cancer treated within 5 years before inclusion except baso-cellular skin&#xD;
             carcinoma or cervical / bladder in situ carcinoma&#xD;
&#xD;
          -  inability to receive study information and to give informed consent&#xD;
&#xD;
          -  patient unable to have a clinical follow-up due to psychological, familial, social or&#xD;
             geographical reasons&#xD;
&#xD;
          -  legal incapacity (people in jail), or under supervision (i.e. guardianship or&#xD;
             curatorship)&#xD;
&#xD;
          -  treatment with experimental drug within 30 days before the start of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Arnaud Scherpereel, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Lille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Arnaud Scherpereel, MD,PhD</last_name>
    <phone>320444998</phone>
    <phone_ext>+33</phone_ext>
    <email>arnaud.scherpereel@chru-lille.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Eric Wasielewski, PhD</last_name>
    <phone>3.20.44.56.12</phone>
    <phone_ext>+33</phone_ext>
    <email>eric.wasielewski@chru-lille.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Institut Coeur-Poumon, CHU</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>May 20, 2020</study_first_submitted>
  <study_first_submitted_qc>May 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <last_update_submitted>January 5, 2023</last_update_submitted>
  <last_update_submitted_qc>January 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Immunotherapy</keyword>
  <keyword>anti-PD-1</keyword>
  <keyword>Photodynamic Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mesothelioma</mesh_term>
    <mesh_term>Mesothelioma, Malignant</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04400539
org study id: 2019_41
secondary id: 2019-003003-35
nct id: NCT04400539
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: the proportion of patients having the full multimodal treatment
time frame: through study completion, an average of 24 months
description: 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.
measure: 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
measure: Kaplan Meier curve for overall survival (mOS)
time frame: through study completion, an average of 24 months
measure: Kaplan Meier curve for progression free survival (mPFS)
time frame: through study completion, an average of 24 months
measure: quality of life (QoL) of patients by dedicated EORTC QLQ C30 (or LCSS-30) questionnaire
time frame: At baseline and
description: 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
measure: evaluation of chest pain using visual scale.
time frame: through study completion, an average of 24 months
arm group label: Malignant Pleural Mesothelioma patients
arm group type: Experimental
intervention type: Device
intervention name: intrapleural photodynamic therapy with videothoracoscopy
description: 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)
arm group label: Malignant Pleural Mesothelioma patients
intervention type: Drug
intervention name: Nivolumab Injection
description: 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.
arm group label: Malignant Pleural Mesothelioma patients
other name: adjuvant immunotherapy with anti-PD-1 Nivolumab antibodies
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Arnaud Scherpereel, MD,PhD
role: Principal Investigator
affiliation: University Hospital, Lille
last name: Arnaud Scherpereel, MD,PhD
phone: 320444998
phone ext: +33
email: arnaud.scherpereel@chru-lille.fr
last name: Eric Wasielewski, PhD
phone: 3.20.44.56.12
phone ext: +33
email: eric.wasielewski@chru-lille.fr
facility: 
status: Recruiting
country: France
responsible party type: Sponsor
mesh term: Mesothelioma
mesh term: Mesothelioma, Malignant
mesh term: Nivolumab