<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/NCT02194231</url>
  </required_header>
  <id_info>
    <org_study_id>IRFMN-MPM-6077</org_study_id>
    <secondary_id>2011-006330-16</secondary_id>
    <nct_id>NCT02194231</nct_id>
  </id_info>
  <brief_title>ATREUS - Phase II Study on the Activity of Trabectedin in Patients With Malignant Pleural Mesothelioma (MPM)</brief_title>
  <acronym>ATREUS</acronym>
  <official_title>ATREUS Trial - A Phase II Study on the Activity of Trabectedin of Pretreated Epithelioid or Biphasic / Sarcomatoid Malignant Pleural Mesothelioma(MPM)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mario Negri Institute for Pharmacological Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>PharmaMar</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Mario Negri Institute for Pharmacological Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether trabectedin is effective in the treatment&#xD;
      of malignant pleural mesothelioma (MPM).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are no approved agents for second-line treatment of MPM in patients who failed first&#xD;
      line pemetrexed plus platinum derivatives regimens. Chemotherapy options are limited and&#xD;
      include gemcitabine, vinorelbine and other antifolate compounds. The role of second-line&#xD;
      chemotherapy is therefore not yet established and second-line patient population is&#xD;
      considered suitable for phase II studies with investigational agents.&#xD;
&#xD;
      Trabectedin is an originally natural marine product, now obtained by a semisynthetic process,&#xD;
      that induces a delay in S phase progression and a blockade in G2 phase of the cell cycle by a&#xD;
      mode of action that seems different from that of other DNA-damaging agents (see citations).&#xD;
      Although the exact mechanism of action of trabectedin has not been fully elucidated yet, it&#xD;
      appears to be unique compared to other anticancer agents (see citations). Trabectedin binds&#xD;
      to N2 of guanines in the minor groove of DNA, causing a bending of the minor groove towards&#xD;
      the major groove.&#xD;
&#xD;
      In the randomised clinical trials in metastatic leiomyosarcoma or liposarcoma and in&#xD;
      recurrent platinum-sensitive ovarian cancer, trabectedin is infused at 1.5 mg/m2 as a 24-hour&#xD;
      infusion or 1.3 mg/m2 as a 3 hour infusion every 3 weeks (see citations). Balancing efficacy&#xD;
      with safety the short infusion is preferable in clinical practice.&#xD;
&#xD;
      In soft tissue sarcoma the response rate did not exceed 10%, however, trabectedin has been&#xD;
      shown to provide disease control, with progression arrest rates exceeding 50% and&#xD;
      progression-free survival rates exceeding 20% at 6 months. In pre-treated ovarian cancer the&#xD;
      objective response rate was 30% with a median time to disease progression of 5.7 months.&#xD;
&#xD;
      Trabectedin has not been extensively employed in MPM, however in phase I studies, some&#xD;
      objective response in heavily pre-treated mesothelioma patients was seen.&#xD;
&#xD;
      The present study is aimed at evaluating the activity of trabectedin in MPM patients not&#xD;
      candidate for radical surgery. This option is of particular interest due to lack of valid&#xD;
      therapeutic options.&#xD;
&#xD;
      Translational studies will be performed to identify factors predictive of the activity of&#xD;
      trabectedin in MPM.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2013</start_date>
  <completion_date type="Actual">December 12, 2019</completion_date>
  <primary_completion_date type="Actual">December 12, 2019</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>Progression Free Survival - PFS12w</measure>
    <time_frame>12 weeks</time_frame>
    <description>Proportion of patients free from progression or death at the second CT scan assessment performed at 12 weeks (Progression Free Survival - PFS12w) from the date of treatment start</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>24 months</time_frame>
    <description>PFS will be evaluated by CT scans every 6 weeks from the date of first treatment until week 12 and subsequently every 8-9 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>24 months</time_frame>
    <description>Responses will be assessed according to Modified RECIST criteria for Malignant Pleural Mesothelioma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trabectedin tolerability and safety</measure>
    <time_frame>24 months</time_frame>
    <description>Safety will be evaluated based on reported AEs, clinical laboratory assessments, vital signs and physical examinations. Adverse events will be encoded using the Medical Dictionary for Regulatory Activities (MedDRA) and graded using NCI-CTCAE ver 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Intensity (PI)</measure>
    <time_frame>24 months</time_frame>
    <description>Pain intensity will be evaluated by using an 11 points Numerical Rating Scale (NRS), where 0 indicates no pain and 10 indicates the worst pain one can imagine. Patients will be requested to evaluate the PI related to the 24 hours preceding the visit and indicating the score for the average, worst and least PI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain type and characteristics</measure>
    <time_frame>24 months</time_frame>
    <description>With special reference to the presence of neuropathic pain, evaluation shall be carried out using the DN4 questionnaire. The global score on this 10 item instrument allows to diagnose the presence of neuropathic pain (total score ≥4)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antalgic treatments</measure>
    <time_frame>24 months</time_frame>
    <description>Evaluation of type and dosage of any pain medication administered to the patient at the moment of the study visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>microRNA (miRs) profile</measure>
    <time_frame>24 months</time_frame>
    <description>miRs profile evaluation will be performed with the aim of characterising the tumour biological features associated to the different response patterns. Since recent published studies suggests that trabectedin modulates the expression of some miRs in cancer cells exposed to the drug and, also, the resistance to anticancer drugs seems to be well correlated to the expression of some specific miRs, the evaluation of miRs expression may become a powerful prognostic and predictive marker.&#xD;
miRNA landscape in both plasma and tumour tissues will be profiled using commercially available oligo arrays platforms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High Mobility Group B1 (HMGB1) protein assessment</measure>
    <time_frame>24 months</time_frame>
    <description>Recent data indicate that the high mobility group B1 (HMGB1) is implicated in the transformation of meshothelial cells and is strongly secreted in sera of patients with mesothelioma. These findings provide the rationale for considering HMGB1 as a potential useful marker to monitor therapeutic effectiveness in patients with mesothelioma.&#xD;
HMGB1 will be determined in plasma of patients at the same time points previously indicated for the assessment of miR profiles by using an ELISA essay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood Macrophages analysis</measure>
    <time_frame>24 months</time_frame>
    <description>We propose to analyse the effects of trabectedin on the number of circulating monocytes and the plasma levels of selected biological mediators. A decrease in the number of circulating monocytes could be a surrogate marker of a biological effect of trabectedin on the precursor cells of tumour macrophages.&#xD;
We propose to collect the number of circulating monocytes during the first 3 treatment cycles, immediately before and 7 days after trabectedin administration</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">145</enrollment>
  <condition>Malignant Pleural Mesothelioma</condition>
  <arm_group>
    <arm_group_label>Trabectedin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive trabectedin treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trabectedin</intervention_name>
    <description>Patients will receive 1.1 mg/m2 intravenous trabectedin infusion in 5% glucose via central venous catheter over 3 hours every 21 days. Trabectedin infusion will be preceded by 20 mg of intravenous dexamethasone</description>
    <arm_group_label>Trabectedin</arm_group_label>
    <other_name>Yondelis</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically proven unresectable MPM. In order to make a reproducible diagnosis, in&#xD;
             particular regarding biphasic MPM, histology must derive from transthoracic biopsies&#xD;
             (at least 3 representative samples) or from videothoracoscopy (at least 5&#xD;
             representative samples)&#xD;
&#xD;
          2. Age &gt;18 years&#xD;
&#xD;
          3. Performance status 0-1 (ECOG)&#xD;
&#xD;
          4. Measurable disease (CT-PET) according to RECIST criteria modified for malignant&#xD;
             pleural mesothelioma&#xD;
&#xD;
          5. Not more than one previous chemotherapy course (consisting of pemetrexed plus platinum&#xD;
             derivative), excluded adjuvant therapy if PFS &lt; 12 months&#xD;
&#xD;
          6. A minimum of 3 weeks since previous tumour directed therapy&#xD;
&#xD;
          7. Recovery from toxic effects of previous therapies to NCI CTC AE Grade 0-1&#xD;
&#xD;
          8. Patients who have received palliative radiation are eligible if &lt;30% of bone marrow&#xD;
             was irradiated and normal haematological function was completely regained&#xD;
&#xD;
          9. Haematologic variables: haemoglobin ≥ 9 g/dL, Absolute neutrophil count (ANC) ≥&#xD;
             1,500/μL and Platelet count ≥ 100,000/μL&#xD;
&#xD;
         10. Serum creatinine ≤1.5 mg/dL or creatinine clearance ≥ 30 mL/min&#xD;
&#xD;
         11. Creatinine phosphokinase (CPK) ≤ 2.5 ULN&#xD;
&#xD;
         12. Hepatic function variables: Total bilirubin ≤ ULN, Total alkaline phosphatase ≤ 2.5&#xD;
             ULN or if &gt; 2.5 ULN alkaline phosphatase liver fraction or GGT or 5' nucleotidase must&#xD;
             be determined and ≤ ULN, AST (serum aspartate transaminase [SGOT]) and ALT (serum&#xD;
             alaninetransaminase [SGPT]) must be ≤ 2.5 x ULN, Albumin ≥ 25 g/L&#xD;
&#xD;
         13. Signed informed consent&#xD;
&#xD;
         14. Adequate contraceptive methods for male patients whose partner is of childbearing&#xD;
             age/potential, during the study and for three months after the end of treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. - Radiotherapy with curative intent to thoracic wall (concomitant with or prior to&#xD;
             chemotherapy)&#xD;
&#xD;
          2. - Uncompensated diabetes mellitus or other condition absolutely contra-indicating&#xD;
             dexamethasone (used as pre-medication)&#xD;
&#xD;
          3. - Patients enrolled in other study with experimental drugs&#xD;
&#xD;
          4. - Women of childbearing age/potential&#xD;
&#xD;
          5. - Prior exposure to trabectedin&#xD;
&#xD;
          6. - History of other malignancies (except basal cell carcinoma or cervical carcinoma in&#xD;
             situ, adequately treated), unless in remission from 5 years or more and judged of&#xD;
             negligible potential of relapse&#xD;
&#xD;
          7. - Active viral hepatitis or chronic liver disease&#xD;
&#xD;
          8. - Unstable cardiac condition, including congestive heart failure or angina pectoris,&#xD;
             myocardial infarction within one year before enrolment, uncontrolled arterial&#xD;
             hypertension or arrhythmias&#xD;
&#xD;
          9. - Active major infection&#xD;
&#xD;
         10. - Other serious concomitant illness&#xD;
&#xD;
         11. - Brain / leptomeningeal involvement&#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>Paolo Bidoli, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda Ospedaliera San Gerardo di Monza</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Valter Torri, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Istituto Di Ricerche Farmacologiche Mario Negri</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Azienda ospedaliera ss. Antonio e Biagio e Cesare Arrigo</name>
      <address>
        <city>Alessandria</city>
        <state>AL</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniche Humanitas Gavazzeni</name>
      <address>
        <city>Bergamo</city>
        <state>BG</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi</name>
      <address>
        <city>Bologna</city>
        <state>Bo</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>P.O. Spedalli Civili</name>
      <address>
        <city>Brescia</city>
        <state>BS</state>
        <zip>25125</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera S. Gerardo di Monza</name>
      <address>
        <city>Monza</city>
        <state>MB</state>
        <zip>20900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <state>MI</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Oncologico Veneto - IOV</name>
      <address>
        <city>Padova</city>
        <state>PD</state>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliro-Universitaria di Parma</name>
      <address>
        <city>Parma</city>
        <zip>43126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <link>
    <url>http://medicine.iupui.edu/flockhart/table.htm</url>
    <description>At this link you may find all the relevant Cytochrome P450 Drud interactions</description>
  </link>
  <results_reference>
    <citation>Pommier Y, Kohlhagen G, Bailly C, Waring M, Mazumder A, Kohn KW. DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata. Biochemistry. 1996 Oct 15;35(41):13303-9. doi: 10.1021/bi960306b.</citation>
    <PMID>8873596</PMID>
  </results_reference>
  <results_reference>
    <citation>Bonfanti M, La Valle E, Fernandez Sousa Faro JM, Faircloth G, Caretti G, Mantovani R, D'Incalci M. Effect of ecteinascidin-743 on the interaction between DNA binding proteins and DNA. Anticancer Drug Des. 1999 Jun;14(3):179-86.</citation>
    <PMID>10500494</PMID>
  </results_reference>
  <results_reference>
    <citation>Erba E, Bergamaschi D, Bassano L, Damia G, Ronzoni S, Faircloth GT, D'Incalci M. Ecteinascidin-743 (ET-743), a natural marine compound, with a unique mechanism of action. Eur J Cancer. 2001 Jan;37(1):97-105. doi: 10.1016/s0959-8049(00)00357-9.</citation>
    <PMID>11165136</PMID>
  </results_reference>
  <results_reference>
    <citation>Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gomez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. doi: 10.1200/JCO.2008.21.0088. Epub 2009 Aug 3.</citation>
    <PMID>19652065</PMID>
  </results_reference>
  <results_reference>
    <citation>Del Campo JM, Roszak A, Bidzinski M, Ciuleanu TE, Hogberg T, Wojtukiewicz MZ, Poveda A, Boman K, Westermann AM, Lebedinsky C; Yondelis Ovarian Cancer Group. Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer. Ann Oncol. 2009 Nov;20(11):1794-802. doi: 10.1093/annonc/mdp198. Epub 2009 Jun 25.</citation>
    <PMID>19556318</PMID>
  </results_reference>
  <results_reference>
    <citation>D'Incalci M, Galmarini CM. A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther. 2010 Aug;9(8):2157-63. doi: 10.1158/1535-7163.MCT-10-0263. Epub 2010 Jul 20.</citation>
    <PMID>20647340</PMID>
  </results_reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 16, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 18, 2014</study_first_posted>
  <last_update_submitted>January 22, 2020</last_update_submitted>
  <last_update_submitted_qc>January 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mesothelioma</keyword>
  <keyword>MPM</keyword>
  <keyword>Trabectedin</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>Trabectedin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>November 6, 2020</submitted>
    <returned>December 4, 2020</returned>
  </pending_results>
  <!-- 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/NCT02194231
org study id: IRFMN-MPM-6077
secondary id: 2011-006330-16
nct id: NCT02194231
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to determine whether trabectedin is effective in the treatment
      of malignant pleural mesothelioma (MPM).
There are no approved agents for second-line treatment of MPM in patients who failed first
      line pemetrexed plus platinum derivatives regimens. Chemotherapy options are limited and
      include gemcitabine, vinorelbine and other antifolate compounds. The role of second-line
      chemotherapy is therefore not yet established and second-line patient population is
      considered suitable for phase II studies with investigational agents.

      Trabectedin is an originally natural marine product, now obtained by a semisynthetic process,
      that induces a delay in S phase progression and a blockade in G2 phase of the cell cycle by a
      mode of action that seems different from that of other DNA-damaging agents (see citations).
      Although the exact mechanism of action of trabectedin has not been fully elucidated yet, it
      appears to be unique compared to other anticancer agents (see citations). Trabectedin binds
      to N2 of guanines in the minor groove of DNA, causing a bending of the minor groove towards
      the major groove.

      In the randomised clinical trials in metastatic leiomyosarcoma or liposarcoma and in
      recurrent platinum-sensitive ovarian cancer, trabectedin is infused at 1.5 mg/m2 as a 24-hour
      infusion or 1.3 mg/m2 as a 3 hour infusion every 3 weeks (see citations). Balancing efficacy
      with safety the short infusion is preferable in clinical practice.

      In soft tissue sarcoma the response rate did not exceed 10%, however, trabectedin has been
      shown to provide disease control, with progression arrest rates exceeding 50% and
      progression-free survival rates exceeding 20% at 6 months. In pre-treated ovarian cancer the
      objective response rate was 30% with a median time to disease progression of 5.7 months.

      Trabectedin has not been extensively employed in MPM, however in phase I studies, some
      objective response in heavily pre-treated mesothelioma patients was seen.

      The present study is aimed at evaluating the activity of trabectedin in MPM patients not
      candidate for radical surgery. This option is of particular interest due to lack of valid
      therapeutic options.

      Translational studies will be performed to identify factors predictive of the activity of
      trabectedin in MPM.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival - PFS12w
time frame: 12 weeks
description: Proportion of patients free from progression or death at the second CT scan assessment performed at 12 weeks (Progression Free Survival - PFS12w) from the date of treatment start
measure: Progression Free Survival (PFS)
time frame: 24 months
description: PFS will be evaluated by CT scans every 6 weeks from the date of first treatment until week 12 and subsequently every 8-9 weeks
measure: Overall survival (OS)
time frame: 24 months
measure: Objective response rate
time frame: 24 months
description: Responses will be assessed according to Modified RECIST criteria for Malignant Pleural Mesothelioma
measure: Trabectedin tolerability and safety
time frame: 24 months
description: Safety will be evaluated based on reported AEs, clinical laboratory assessments, vital signs and physical examinations. Adverse events will be encoded using the Medical Dictionary for Regulatory Activities (MedDRA) and graded using NCI-CTCAE ver 4
measure: Pain Intensity (PI)
time frame: 24 months
description: Pain intensity will be evaluated by using an 11 points Numerical Rating Scale (NRS), where 0 indicates no pain and 10 indicates the worst pain one can imagine. Patients will be requested to evaluate the PI related to the 24 hours preceding the visit and indicating the score for the average, worst and least PI
measure: Pain type and characteristics
time frame: 24 months
description: With special reference to the presence of neuropathic pain, evaluation shall be carried out using the DN4 questionnaire. The global score on this 10 item instrument allows to diagnose the presence of neuropathic pain (total score ≥4)
measure: Antalgic treatments
time frame: 24 months
description: Evaluation of type and dosage of any pain medication administered to the patient at the moment of the study visit
measure: microRNA (miRs) profile
time frame: 24 months
description: miRs profile evaluation will be performed with the aim of characterising the tumour biological features associated to the different response patterns. Since recent published studies suggests that trabectedin modulates the expression of some miRs in cancer cells exposed to the drug and, also, the resistance to anticancer drugs seems to be well correlated to the expression of some specific miRs, the evaluation of miRs expression may become a powerful prognostic and predictive marker.
miRNA landscape in both plasma and tumour tissues will be profiled using commercially available oligo arrays platforms.
measure: High Mobility Group B1 (HMGB1) protein assessment
time frame: 24 months
description: Recent data indicate that the high mobility group B1 (HMGB1) is implicated in the transformation of meshothelial cells and is strongly secreted in sera of patients with mesothelioma. These findings provide the rationale for considering HMGB1 as a potential useful marker to monitor therapeutic effectiveness in patients with mesothelioma.
HMGB1 will be determined in plasma of patients at the same time points previously indicated for the assessment of miR profiles by using an ELISA essay
measure: Blood Macrophages analysis
time frame: 24 months
description: We propose to analyse the effects of trabectedin on the number of circulating monocytes and the plasma levels of selected biological mediators. A decrease in the number of circulating monocytes could be a surrogate marker of a biological effect of trabectedin on the precursor cells of tumour macrophages.
We propose to collect the number of circulating monocytes during the first 3 treatment cycles, immediately before and 7 days after trabectedin administration
arm group label: Trabectedin
arm group type: Experimental
description: Patients will receive trabectedin treatment
intervention type: Drug
intervention name: Trabectedin
description: Patients will receive 1.1 mg/m2 intravenous trabectedin infusion in 5% glucose via central venous catheter over 3 hours every 21 days. Trabectedin infusion will be preceded by 20 mg of intravenous dexamethasone
arm group label: Trabectedin
other name: Yondelis
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paolo Bidoli, MD
role: Principal Investigator
affiliation: Azienda Ospedaliera San Gerardo di Monza
last name: Valter Torri, MD
role: Study Chair
affiliation: Istituto Di Ricerche Farmacologiche Mario Negri
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Italy
url: http://medicine.iupui.edu/flockhart/table.htm
description: At this link you may find all the relevant Cytochrome P450 Drud interactions
citation: Pommier Y, Kohlhagen G, Bailly C, Waring M, Mazumder A, Kohn KW. DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata. Biochemistry. 1996 Oct 15;35(41):13303-9. doi: 10.1021/bi960306b.
PMID: 8873596
citation: Bonfanti M, La Valle E, Fernandez Sousa Faro JM, Faircloth G, Caretti G, Mantovani R, D'Incalci M. Effect of ecteinascidin-743 on the interaction between DNA binding proteins and DNA. Anticancer Drug Des. 1999 Jun;14(3):179-86.
PMID: 10500494
citation: Erba E, Bergamaschi D, Bassano L, Damia G, Ronzoni S, Faircloth GT, D'Incalci M. Ecteinascidin-743 (ET-743), a natural marine compound, with a unique mechanism of action. Eur J Cancer. 2001 Jan;37(1):97-105. doi: 10.1016/s0959-8049(00)00357-9.
PMID: 11165136
citation: Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gomez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. doi: 10.1200/JCO.2008.21.0088. Epub 2009 Aug 3.
PMID: 19652065
citation: Del Campo JM, Roszak A, Bidzinski M, Ciuleanu TE, Hogberg T, Wojtukiewicz MZ, Poveda A, Boman K, Westermann AM, Lebedinsky C; Yondelis Ovarian Cancer Group. Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer. Ann Oncol. 2009 Nov;20(11):1794-802. doi: 10.1093/annonc/mdp198. Epub 2009 Jun 25.
PMID: 19556318
citation: D'Incalci M, Galmarini CM. A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther. 2010 Aug;9(8):2157-63. doi: 10.1158/1535-7163.MCT-10-0263. Epub 2010 Jul 20.
PMID: 20647340
responsible party type: Sponsor
mesh term: Mesothelioma
mesh term: Mesothelioma, Malignant
mesh term: Trabectedin
sharing ipd: Yes
submitted: November 6, 2020
returned: December 4, 2020