<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/NCT03269227</url>
  </required_header>
  <id_info>
    <org_study_id>IRST163.01</org_study_id>
    <nct_id>NCT03269227</nct_id>
  </id_info>
  <brief_title>Accelerated Hypofractionated Radiotherapy in the Treatment of Malignant Pleural Mesothelioma</brief_title>
  <acronym>MesoRT</acronym>
  <official_title>Accelerated Hypofractionated Radiotherapy in the Treatment of Malignant Pleural Mesothelioma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori</source>
  <oversight_info>
    <has_dmc>No</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>
      This is a monocentric prospective study of radiotherapy using accelerated hypofractionation&#xD;
      with Tomotherapy in Malignant Pleural Mesothelioma (MPM) patients after pleurectomy /&#xD;
      decortication (P / D) or biopsy.&#xD;
&#xD;
      The treatment will be delivered using Tomotherapy, that allows to adopt dose accelerated&#xD;
      hypofraction criteria. Treatment duration is 5 consecutive days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The role of radiation therapy remains to be defined in unresected MPM or after P/D. For the&#xD;
      latter, local control remains the primary objective but radiotherapy (RT) is a challenge&#xD;
      because of the risk of pneumonia in the intact lung. There are no specific clinical data to&#xD;
      support the use of adjuvant radiation therapy after P/D or definitive radiation therapy after&#xD;
      biopsy-based diagnosis for patients not amenable to surgery.&#xD;
&#xD;
      However, recent publications on Intensity Modulated Radiotherapy (IMRT) and conventional&#xD;
      fractionation after P/D or biopsy have shown the feasibility and acceptable toxicity profile&#xD;
      of the treatment.&#xD;
&#xD;
      The investigators submitted a retrospective analysis of accelerated hypofractionated&#xD;
      Intensity modulated arc therapy (IMAT) using TomoTherapy in MPM following P/D or diagnostic&#xD;
      biopsy. In the investigators experience of MPM, treatment of the intact lung with pleural&#xD;
      IMAT using helical Tomotherapy is a safe and feasible option with an acceptable lung toxicity&#xD;
      profile. The results obtained in terms of toxicity were encouraging. In fact, the&#xD;
      investigators only observed one case of G3 pneumonia, and the patient in question is still&#xD;
      alive and off oxygen therapy. Patient compliance with this short-course treatment was also&#xD;
      very good.&#xD;
&#xD;
      Overall, the investigators found that accelerated hypofractionation with IMAT was feasible at&#xD;
      the dose delivered and had an acceptable toxicity profile. So the investigators want to&#xD;
      propose this protocol for treatment of MPM in intact lung to improve local control.&#xD;
&#xD;
      In patients with malignant pleural mesothelioma who underwent pleurectomy / decortications&#xD;
      (P/D) or only diagnostic biopsy, it is difficult to deliver a tumoricidal dose of radiation&#xD;
      to the pleura due to the presence of the ipsilateral lung. In recent years, the investigators&#xD;
      have implemented a technique for irradiation of the pleura in intact lung, using accelerated&#xD;
      hypofractionation with Tomotherapy in an attempt to reduce as far as possible, the dose to&#xD;
      the ipsilateral lung. The aim of the treatment was palliation. The investigators analyzed the&#xD;
      data of 36 patients with MPM, with a long follow-up without recording death cases related to&#xD;
      radiation treatment or radiation pneumonitis grade 4.&#xD;
&#xD;
      In view of these data, the aim of this study is to increase the dose of treatment in patients&#xD;
      suffering from MPM after P/D or biopsy.&#xD;
&#xD;
      The study will evaluate the feasibility of the treatment through the study of pulmonary acute&#xD;
      and late toxicity; The treatment will be delivered using Tomotherapy that allows to adopt&#xD;
      dose accelerated hypofraction criteria. Treatment duration is 5 consecutive days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 14, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>N/A</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>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]</measure>
    <time_frame>up to 36 months</time_frame>
    <description>Acute and late toxicity evaluation by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, performing strumental tests (CT scan, spirometry) to evaluate adverse events including pulmonary toxicity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>up to 36 months</time_frame>
    <description>time from randomization until death for any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>up to 36 months</time_frame>
    <description>the assessment of disease control rate (DCR) defined as proportion of patients with complete response (CR), partial response (PR) and stable disease (SD) for patients with evaluable disease using the Modified RECIST criteria for assessment of response in malignant pleural mesotelioma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to progessione (TTP)</measure>
    <time_frame>up to 36 months</time_frame>
    <description>calculation of time to progression (TTP) for patients without evidence of disease or with not evaluable disease</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Malignant Pleural Mesothelioma</condition>
  <arm_group>
    <arm_group_label>Accelerated hypofractionation with Tomotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tomotherapy Treatment Planning System (TPS) will be used for treatment plannings.&#xD;
Patient' set-up daily control through Tomo-image (CT megavoltage) immediately before each sitting of all the patients.&#xD;
Prescription dose to the target: 30 Gy in 5 daily fraction (at the reference isodose 60-70%) with an internal increasing inhomogenous dose of up to 37.5 Gy-40 Gy for Gross Tumor Volume (GTV).</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Accelerated hypofractionation with Tomotherapy</intervention_name>
    <description>Tomotherapy TPS will be used for treatment plannings. Patient' set-up daily control through Tomo-image (CT megavoltage) immediately before each sitting of all the patients.&#xD;
Prescription doses:&#xD;
Prescription dose to the target: 30 Gy in 5 daily fraction (at the reference isodose 60-70%) with an internal increasing inhomogenous dose of up to 37.5 Gy-40 Gy for GTV.&#xD;
Steroids (methylprednisolone 4 mg daily) should be used from day 1 of radiotherapy to day + 30 after the end of the treatment.</description>
    <arm_group_label>Accelerated hypofractionation with Tomotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have histologically or cytologically confirmed MPM&#xD;
&#xD;
          2. Karnofsky Performance status scale 70-100 (see Appendix B)&#xD;
&#xD;
          3. Male or female, Aged &gt;= 18 and ≤ 85 years&#xD;
&#xD;
          4. Life expectancy greater than 6 months&#xD;
&#xD;
          5. All clinical and pathological stage with the exclusion of contralateral mediastinum&#xD;
             involvement (N3) and M1&#xD;
&#xD;
          6. Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
               -  leukocytes &gt;3,000/microL&#xD;
&#xD;
               -  absolute neutrophil count &gt;1,500/microL&#xD;
&#xD;
               -  platelets &gt;100,000/microL&#xD;
&#xD;
               -  aspartate transaminase(AST)/alanine transaminase (ALT) &lt;2.5 X institutional upper&#xD;
                  limit of normal&#xD;
&#xD;
               -  creatinine within normal institutional limits&#xD;
&#xD;
               -  glycemia &lt; 100 mg/dl&#xD;
&#xD;
          7. Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
          8. Forced expiratory volume in the 1st second(FEV1) ≥ 50&#xD;
&#xD;
          9. Patients after biopsy must have measurable disease defined as at least one lesion that&#xD;
             can be accurately measured according to modified RECIST criteria; for resected&#xD;
             patients no more than 3 months are allowed for RT start.&#xD;
&#xD;
         10. Written informed consent signed and dated before starting study procedure.&#xD;
&#xD;
         11. Female participants of child bearing potential and male participants whose partner is&#xD;
             of child bearing potential must be willing to ensure that they or their partner use&#xD;
             effective contraception during the study and for 4 months thereafter.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous thorax radiotherapy&#xD;
&#xD;
          2. Chemotherapy is allowed but completed 3 weeks before RT starts&#xD;
&#xD;
          3. Participation in another clinical trial with any investigational agents within 30 days&#xD;
             prior to study screening.&#xD;
&#xD;
          4. Patients with M1 have to be excluded to this study&#xD;
&#xD;
          5. FEV1 &lt; 50&#xD;
&#xD;
          6. Age &gt;85 years old&#xD;
&#xD;
          7. Respiratory needing oxygen therapy&#xD;
&#xD;
          8. Interstitial pneumopathy&#xD;
&#xD;
          9. Active pneumonitis&#xD;
&#xD;
         10. Fissural disease&#xD;
&#xD;
         11. Contralateral mediastinum involvement (N3) and M1&#xD;
&#xD;
         12. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elisabetta Parisi, MD</last_name>
    <role>Study Director</role>
    <affiliation>Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Via Maroncelli 40, 47014 Meldola, ITALY</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Oriana Nanni</last_name>
    <phone>+39 0543 739266</phone>
    <email>oriana.nanni@irst.emr.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>SC Radiotherapy</name>
      <address>
        <city>Meldola</city>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elisabetta Parisi, MD</last_name>
      <phone>0543 7391100</phone>
      <email>elisabetta.parisi@irst.emr.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>May 26, 2023</last_update_submitted>
  <last_update_submitted_qc>May 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Malignant Pleural Mesothelioma</keyword>
  <keyword>Radiotherapy</keyword>
  <keyword>Tomotherapy</keyword>
  <keyword>Hypofractionation</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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03269227
org study id: IRST163.01
nct id: NCT03269227
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a monocentric prospective study of radiotherapy using accelerated hypofractionation
      with Tomotherapy in Malignant Pleural Mesothelioma (MPM) patients after pleurectomy /
      decortication (P / D) or biopsy.

      The treatment will be delivered using Tomotherapy, that allows to adopt dose accelerated
      hypofraction criteria. Treatment duration is 5 consecutive days.
The role of radiation therapy remains to be defined in unresected MPM or after P/D. For the
      latter, local control remains the primary objective but radiotherapy (RT) is a challenge
      because of the risk of pneumonia in the intact lung. There are no specific clinical data to
      support the use of adjuvant radiation therapy after P/D or definitive radiation therapy after
      biopsy-based diagnosis for patients not amenable to surgery.

      However, recent publications on Intensity Modulated Radiotherapy (IMRT) and conventional
      fractionation after P/D or biopsy have shown the feasibility and acceptable toxicity profile
      of the treatment.

      The investigators submitted a retrospective analysis of accelerated hypofractionated
      Intensity modulated arc therapy (IMAT) using TomoTherapy in MPM following P/D or diagnostic
      biopsy. In the investigators experience of MPM, treatment of the intact lung with pleural
      IMAT using helical Tomotherapy is a safe and feasible option with an acceptable lung toxicity
      profile. The results obtained in terms of toxicity were encouraging. In fact, the
      investigators only observed one case of G3 pneumonia, and the patient in question is still
      alive and off oxygen therapy. Patient compliance with this short-course treatment was also
      very good.

      Overall, the investigators found that accelerated hypofractionation with IMAT was feasible at
      the dose delivered and had an acceptable toxicity profile. So the investigators want to
      propose this protocol for treatment of MPM in intact lung to improve local control.

      In patients with malignant pleural mesothelioma who underwent pleurectomy / decortications
      (P/D) or only diagnostic biopsy, it is difficult to deliver a tumoricidal dose of radiation
      to the pleura due to the presence of the ipsilateral lung. In recent years, the investigators
      have implemented a technique for irradiation of the pleura in intact lung, using accelerated
      hypofractionation with Tomotherapy in an attempt to reduce as far as possible, the dose to
      the ipsilateral lung. The aim of the treatment was palliation. The investigators analyzed the
      data of 36 patients with MPM, with a long follow-up without recording death cases related to
      radiation treatment or radiation pneumonitis grade 4.

      In view of these data, the aim of this study is to increase the dose of treatment in patients
      suffering from MPM after P/D or biopsy.

      The study will evaluate the feasibility of the treatment through the study of pulmonary acute
      and late toxicity; The treatment will be delivered using Tomotherapy that allows to adopt
      dose accelerated hypofraction criteria. Treatment duration is 5 consecutive days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
time frame: up to 36 months
description: Acute and late toxicity evaluation by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, performing strumental tests (CT scan, spirometry) to evaluate adverse events including pulmonary toxicity
measure: Overall survival (OS)
time frame: up to 36 months
description: time from randomization until death for any cause
measure: Disease control rate (DCR)
time frame: up to 36 months
description: the assessment of disease control rate (DCR) defined as proportion of patients with complete response (CR), partial response (PR) and stable disease (SD) for patients with evaluable disease using the Modified RECIST criteria for assessment of response in malignant pleural mesotelioma
measure: time to progessione (TTP)
time frame: up to 36 months
description: calculation of time to progression (TTP) for patients without evidence of disease or with not evaluable disease
arm group label: Accelerated hypofractionation with Tomotherapy
arm group type: Experimental
description: Tomotherapy Treatment Planning System (TPS) will be used for treatment plannings.
Patient' set-up daily control through Tomo-image (CT megavoltage) immediately before each sitting of all the patients.
Prescription dose to the target: 30 Gy in 5 daily fraction (at the reference isodose 60-70%) with an internal increasing inhomogenous dose of up to 37.5 Gy-40 Gy for Gross Tumor Volume (GTV).
intervention type: Radiation
intervention name: Accelerated hypofractionation with Tomotherapy
description: Tomotherapy TPS will be used for treatment plannings. Patient' set-up daily control through Tomo-image (CT megavoltage) immediately before each sitting of all the patients.
Prescription doses:
Prescription dose to the target: 30 Gy in 5 daily fraction (at the reference isodose 60-70%) with an internal increasing inhomogenous dose of up to 37.5 Gy-40 Gy for GTV.
Steroids (methylprednisolone 4 mg daily) should be used from day 1 of radiotherapy to day + 30 after the end of the treatment.
arm group label: Accelerated hypofractionation with Tomotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Elisabetta Parisi, MD
role: Study Director
affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Via Maroncelli 40, 47014 Meldola, ITALY
last name: Oriana Nanni
phone: +39 0543 739266
email: oriana.nanni@irst.emr.it
facility: 
status: Recruiting
contact: 
country: Italy
responsible party type: Sponsor
mesh term: Mesothelioma
mesh term: Mesothelioma, Malignant
sharing ipd: Undecided