<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/NCT03838744</url>
  </required_header>
  <id_info>
    <org_study_id>ISG-TOMAS 2</org_study_id>
    <nct_id>NCT03838744</nct_id>
  </id_info>
  <brief_title>Randomized Trial in Advanced, Metastatic or Unresectable Soft Tissue Sarcoma After Failure of Standard Treatments.</brief_title>
  <acronym>TOMAS2</acronym>
  <official_title>Phase 2 Randomized Trial of Trabectedin + Olaparib vs. Trabectedin in Advanced, Metastatic or Unresectable Soft Tissue Sarcoma After Failure of Standard Treatments.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Italian Sarcoma Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>PharmaMar</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Italian Sarcoma Group</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>
      Phase II study in patient with advanced Soft Tissue Sarcoma (STS) patients who have already&#xD;
      received or are not suitable, for a doxorubicin-based treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Randomized, open-label, active-controlled, multicenter phase II clinical study. Patients will&#xD;
      be randomly assigned in a 1:1 ratio to receive trabectedin 1.1 mg/m2 24-hour intravenous&#xD;
      continuous infusion every 3 weeks with olaparib (per os) 150 mg twice a day versus&#xD;
      trabectedin 1.5 mg/m2 intravenous 24-hour continuous infusion every 3 weeks until progression&#xD;
      or unacceptable toxicity as second- or further-line treatment in a population of STS patients&#xD;
      who have already received or are not suitable for a doxorubicin-based treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 26, 2020</start_date>
  <completion_date type="Anticipated">February 2025</completion_date>
  <primary_completion_date type="Anticipated">February 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Controlled, parallel, two arm study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free Survival (PFS)</measure>
    <time_frame>At 6 months</time_frame>
    <description>Survival without disease progression</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>At 3 years</time_frame>
    <description>Survival from the first dose treatment to death for any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival rate</measure>
    <time_frame>At 12 months</time_frame>
    <description>Proportion of patients who are still alive at 12 months after have started the treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free Survival (PFS)</measure>
    <time_frame>At 3 years</time_frame>
    <description>Survival without disease progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free Survival Rate</measure>
    <time_frame>At 6 months</time_frame>
    <description>Proportion of patients who did not progress at 6 months after have started the treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Growth Modulation Index (GMI)</measure>
    <time_frame>Week 6, week 12, week 18, week 27, week 36</time_frame>
    <description>Ratio of time to progression with the nth line of therapy to the those with the n-1th line.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events related to the treatment</measure>
    <time_frame>Week 3, week6, week 9, week 12, week 18, week 27, week 36</time_frame>
    <description>Safety in term of adverse event is evaluate from the firs treatment dose throughout the study according to CTCAE 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life according the 30 questions European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC Quality of Life Questionnaire C30)</measure>
    <time_frame>Week 3, week6, week 9, week 12, week 18, week 27, week 36</time_frame>
    <description>Evaluation of the quality of life collected with EORTC Quality of Life Questionnaire C30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life according the questionnaire Euro Quality Of Life 5 Domains (EQ-5D)</measure>
    <time_frame>Week 3, week6, week 9, week 12, week 18, week 27, week 36</time_frame>
    <description>Evaluation of the quality of life collected with EQ-5D</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Over all Response Rate</measure>
    <time_frame>At week 18</time_frame>
    <description>Overall response rate according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">126</enrollment>
  <condition>Advanced Soft Tissue Sarcoma</condition>
  <arm_group>
    <arm_group_label>Standard arm: Trabectedin in monotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Trabectedin in monotherapy at the dose 1.5 or 1.3 mg/m2 (according institutional practice) given as intravenous infusion at day 1 every 3 weeks (21 days cycle)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental arm: Trabectedin + Olaparib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trabectedin at the dose 1.1mg/m2 given as intravenous infusion at day 1 every 3 weeks (21 days cycle) plus Olaparib per os at the dose of 150 mg twice a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard arm: Trabectedin in monotherapy</intervention_name>
    <description>Trabectedin in monotherapy</description>
    <arm_group_label>Standard arm: Trabectedin in monotherapy</arm_group_label>
    <other_name>Trabectedin arm</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Experimental arm: Trabectedin + Olaparib</intervention_name>
    <description>Trabectedin given in combination to olaparib</description>
    <arm_group_label>Experimental arm: Trabectedin + Olaparib</arm_group_label>
    <other_name>Trabectedin+ Olaparib arm</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of written informed consent prior to any study specific procedures.&#xD;
&#xD;
          -  Patients with histologically documented and not surgically resectable or metastatic&#xD;
             STS that progressed after first- or further-line treatments for relapsing disease.&#xD;
&#xD;
          -  At least one previous line of anthracycline-containing chemotherapy for advanced&#xD;
             disease or relapsed/progressed within six months of a previous treatment with an&#xD;
             anthracycline-containing chemotherapy in the neo-adjuvant/adjuvant setting.&#xD;
&#xD;
          -  Central revision will be mandatory in order to enroll a patient. Central revision will&#xD;
             assess both diagnosis and adequacy of tumor specimen (minimum requisite will be a&#xD;
             formalin-fixed paraffin-embedded block of either a 16-gauge tru-cut biopsy or a&#xD;
             non-necrotic surgical tumor specimen). The patient has to consent BReast CAncer genes&#xD;
             1 and 2 (BRCA1 and BRCA 2) evaluation in the interest of avoiding misleading&#xD;
             interpretation of resulting data.&#xD;
&#xD;
          -  Measurable disease according Response Evaluation Criteria in Solid Tumors (RECIST) 1.1&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Patients with&#xD;
             an ECOG 2 are eligible if it depends solely on orthopedic problems.&#xD;
&#xD;
          -  Estimated life expectancy of at least 16 weeks.&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  Left Ventricular Ejection Fraction ≥ 50% and/or above lower institutional limit of&#xD;
             normality&#xD;
&#xD;
          -  Adequate bone marrow, liver and renal function assessed within 7 days prior to&#xD;
&#xD;
          -  Postmenopausal or evidence of non-childbearing status for women of childbearing&#xD;
             potential: negative urine or serum pregnancy test within 28 days of study treatment&#xD;
             and confirmed prior to treatment on day 1&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous enrolment in the present study&#xD;
&#xD;
          -  Participation in another clinical study with an investigational product during the&#xD;
             last 4 weeks.&#xD;
&#xD;
          -  Previous treatment with trabectedin, olaparib or other Poly Adpribose polymerase 1&#xD;
             (PARP-1) inhibitors or analogue.&#xD;
&#xD;
          -  Persistent toxicities (≥ grade 2 according Common Terminology Criteria for Adverse&#xD;
             Events - CTCAE) with the exception of alopecia, caused by previous anticancer&#xD;
             therapies.&#xD;
&#xD;
          -  Dementia or significantly altered mental status (e.g., psychiatric disorder) that&#xD;
             would prevent the understanding or rendering of informed consent and compliance with&#xD;
             the requirements of this protocol.&#xD;
&#xD;
          -  Patients with any severe and/or uncontrolled medical conditions such as unstable&#xD;
             angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6&#xD;
             months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, active&#xD;
             or uncontrolled severe infection, cirrhosis, chronic or persistent active hepatitis or&#xD;
             severely impaired lung function. In particular for history of cardiac disease:&#xD;
             congestive heart failure &gt;New York Hearth Association (NYHA) class 2; active coronary&#xD;
             artery disease (myocardial infarction more than 6 months prior to study entry is&#xD;
             allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or&#xD;
             digoxin are permitted) or uncontrolled hypertension, unstable spinal cord compression&#xD;
             (untreated and unstable for at least 28 days prior to study entry), superior vena cava&#xD;
             syndrome, extensive bilateral lung disease.&#xD;
&#xD;
          -  Immunocompromised patients, e.g., patients who are known to be serologically positive&#xD;
             for Human Immunodeficiency Virus (HIV).&#xD;
&#xD;
          -  Active clinically serious infections (&gt; grade 2 CTCAE).&#xD;
&#xD;
          -  Active viral hepatitis [Hepatitis B Virus - (HBV) or Hepatitis C Virus (HCV)&#xD;
             infection]&#xD;
&#xD;
          -  Metastatic brain or meningeal tumors (unless the patient is &gt; 6 months from definitive&#xD;
             therapy, does not require corticosteroid treatment, has a negative imaging study&#xD;
             within 4 weeks of study entry and is clinically stable with respect to the tumor at&#xD;
             the time of study entry). Patients with spinal cord compression unless considered to&#xD;
             have received definitive treatment for this and evidence of clinically stable disease&#xD;
             for 28 days.&#xD;
&#xD;
          -  Patients with seizure disorders requiring medication (such as steroids or&#xD;
             anti-epileptics).&#xD;
&#xD;
          -  Pregnant or breast-feeding patients. Women of childbearing potential must have a&#xD;
             negative pregnancy test performed within 28 days before the start of treatment.&#xD;
             Pregnancy test will be repeated and confirmed on cycle 1 day 1 before treatment start.&#xD;
             Both men and women enrolled in this trial must use adequate barrier birth control&#xD;
             measures during the course of the trial and 5 months after last dose of study drug.&#xD;
&#xD;
          -  Patients with evidence or history of bleeding diathesis.&#xD;
&#xD;
          -  Patients undergoing renal dialysis.&#xD;
&#xD;
          -  Patients unable to swallow oral medications.&#xD;
&#xD;
          -  Uncontrolled diabetes (fasting glucose &gt; 2 x Upper Normal Limit).&#xD;
&#xD;
          -  Patients receiving chronic, systemic treatment with corticosteroids or another&#xD;
             immunosuppressive agent (except corticosteroids with a daily dosage equivalent to&#xD;
             prednisone ≤ 20 mg for adrenal insufficiency). Topical or inhaled corticosteroids are&#xD;
             permitted.&#xD;
&#xD;
          -  Other malignancy unless curatively treated with no evidence of disease for ≥5 years&#xD;
             except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer&#xD;
             of the cervix, ductal carcinoma in situ , Stage 1, grade 1 endometrial carcinoma.&#xD;
             Patients with a history of localised triple negative breast cancer may be eligible,&#xD;
             provided they completed their adjuvant chemotherapy more than three years prior to&#xD;
             registration, and that the patient remains free of recurrent or metastatic disease&#xD;
&#xD;
          -  Patients with severe and/or uncontrolled concurrent medical disease that in the&#xD;
             opinion of the investigator could cause unacceptable safety risks or compromise&#xD;
             compliance with the protocol (e.g. impairment of gastrointestinal (GI) function, or GI&#xD;
             disease that may significantly alter the absorption of the study drugs).&#xD;
&#xD;
          -  Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study&#xD;
             entry&#xD;
&#xD;
          -  Radiotherapy during study or within 3 weeks of start of study drug. (Palliative&#xD;
             radiotherapy will be allowed).&#xD;
&#xD;
          -  Major surgery within 4 weeks of start of study. Thus, patients must have recovered&#xD;
             from wound or directly surgical related complications at time of study randomization.&#xD;
&#xD;
          -  Investigational drug therapy outside of this trial during or within 4 weeks of study&#xD;
             entry.&#xD;
&#xD;
          -  Patients with known hypersensitivity to trabectedin, olaparib or to their excipients.&#xD;
&#xD;
          -  Patients can receive a stable dose of bisphosphonates for bone metastases before and&#xD;
             during the study as long as these were started at least 4 weeks prior to treatment&#xD;
             with the study drugs.&#xD;
&#xD;
          -  Substance abuse, medical, psychological or social conditions that may interfere with&#xD;
             the patient's participation in the study or evaluation of the study results.&#xD;
&#xD;
          -  A history of noncompliance to medical regimens or inability or unwillingness to return&#xD;
             for scheduled visits.&#xD;
&#xD;
          -  Resting ElectroCardioGram (ECG) indicating uncontrolled, potentially reversible&#xD;
             cardiac conditions, as judged by the investigator (eg., unstable ischemia,&#xD;
             uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT&#xD;
             prolongation &gt;500 ms, electrolyte disturbances, etc.), or patients with congenital&#xD;
             long QT syndrome.&#xD;
&#xD;
          -  Concomitant use of known strong CYtochromeP3A (CYP3A) inhibitors (eg. itraconazole,&#xD;
             telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or&#xD;
             cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate&#xD;
             CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil).&#xD;
             The required washout period prior to starting study drugs is 2 weeks.&#xD;
&#xD;
          -  Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin,&#xD;
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or&#xD;
             moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout&#xD;
             period prior to starting study drugs is 5 weeks for enzalutamide or phenobarbital and&#xD;
             3 weeks for other agents.&#xD;
&#xD;
          -  Previous allogenic bone marrow transplant or double umbilical cord blood&#xD;
             transplantation&#xD;
&#xD;
          -  Patients with myelodysplastic syndrome/acute myeloid leukemia or with features&#xD;
             suggestive of them&#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>Giovanni Giovanni, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione del Piemonte IRCCS di Candiolo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Di Bologna</name>
      <address>
        <city>Bologna</city>
        <state>BO</state>
        <zip>40139</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>I.R.S.T. di Meldola</name>
      <address>
        <city>Meldola</city>
        <state>FC</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nuovo Ospedale di Prato</name>
      <address>
        <city>Prato</city>
        <state>Firenze</state>
        <zip>59100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale dei Tumori</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Paolo Giaccone</name>
      <address>
        <city>Palermo</city>
        <state>PA</state>
        <zip>90127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro di Riferimento Oncologico di Aviano</name>
      <address>
        <city>Aviano</city>
        <state>PD</state>
        <zip>33081</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario Campus Biomedico</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione del Piemonte per l'Oncologia IRCC Candiolo</name>
      <address>
        <city>Candiolo</city>
        <state>Torino</state>
        <zip>10060</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Giovanni Bosco</name>
      <address>
        <city>Torino</city>
        <state>TO</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors</name>
      <address>
        <city>Bologna</city>
        <zip>40136</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irccs Istituto Oncologico Veneto (Iov)</name>
      <address>
        <city>Padova</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori Regina Elena - Unit of Medical Oncology I</name>
      <address>
        <city>Roma</city>
        <zip>00144</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Grignani G, D'Ambrosio L, Pignochino Y, Palmerini E, Zucchetti M, Boccone P, Aliberti S, Stacchiotti S, Bertulli R, Piana R, Miano S, Tolomeo F, Chiabotto G, Sangiolo D, Pisacane A, Dei Tos AP, Novara L, Bartolini A, Marchesi E, D'Incalci M, Bardelli A, Picci P, Ferrari S, Aglietta M. Trabectedin and olaparib in patients with advanced and non-resectable bone and soft-tissue sarcomas (TOMAS): an open-label, phase 1b study from the Italian Sarcoma Group. Lancet Oncol. 2018 Oct;19(10):1360-1371. doi: 10.1016/S1470-2045(18)30438-8. Epub 2018 Sep 11.</citation>
    <PMID>30217671</PMID>
  </reference>
  <reference>
    <citation>Samuels BL, Chawla S, Patel S, von Mehren M, Hamm J, Kaiser PE, Schuetze S, Li J, Aymes A, Demetri GD. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Ann Oncol. 2013 Jun;24(6):1703-9. doi: 10.1093/annonc/mds659. Epub 2013 Feb 5.</citation>
    <PMID>23385197</PMID>
  </reference>
  <reference>
    <citation>Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. doi: 10.1016/S1470-2045(16)30376-X. Epub 2016 Sep 9.</citation>
    <PMID>27617661</PMID>
  </reference>
  <reference>
    <citation>Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. Epub 2017 Jul 25. Erratum In: Lancet Oncol. 2017 Sep;18(9):e510.</citation>
    <PMID>28754483</PMID>
  </reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>February 11, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Soft tissue sarcoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Olaparib</mesh_term>
    <mesh_term>Trabectedin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03838744
org study id: ISG-TOMAS 2
nct id: NCT03838744
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Phase II study in patient with advanced Soft Tissue Sarcoma (STS) patients who have already
      received or are not suitable, for a doxorubicin-based treatment.
Randomized, open-label, active-controlled, multicenter phase II clinical study. Patients will
      be randomly assigned in a 1:1 ratio to receive trabectedin 1.1 mg/m2 24-hour intravenous
      continuous infusion every 3 weeks with olaparib (per os) 150 mg twice a day versus
      trabectedin 1.5 mg/m2 intravenous 24-hour continuous infusion every 3 weeks until progression
      or unacceptable toxicity as second- or further-line treatment in a population of STS patients
      who have already received or are not suitable for a doxorubicin-based treatment.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Controlled, parallel, two arm study
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free Survival (PFS)
time frame: At 6 months
description: Survival without disease progression
measure: Overall Survival (OS)
time frame: At 3 years
description: Survival from the first dose treatment to death for any cause
measure: Overall Survival rate
time frame: At 12 months
description: Proportion of patients who are still alive at 12 months after have started the treatment
measure: Progression free Survival (PFS)
time frame: At 3 years
description: Survival without disease progression
measure: Progression free Survival Rate
time frame: At 6 months
description: Proportion of patients who did not progress at 6 months after have started the treatment
measure: Growth Modulation Index (GMI)
time frame: Week 6, week 12, week 18, week 27, week 36
description: Ratio of time to progression with the nth line of therapy to the those with the n-1th line.
measure: Adverse events related to the treatment
time frame: Week 3, week6, week 9, week 12, week 18, week 27, week 36
description: Safety in term of adverse event is evaluate from the firs treatment dose throughout the study according to CTCAE 5.0
measure: Quality of Life according the 30 questions European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC Quality of Life Questionnaire C30)
time frame: Week 3, week6, week 9, week 12, week 18, week 27, week 36
description: Evaluation of the quality of life collected with EORTC Quality of Life Questionnaire C30
measure: Quality of Life according the questionnaire Euro Quality Of Life 5 Domains (EQ-5D)
time frame: Week 3, week6, week 9, week 12, week 18, week 27, week 36
description: Evaluation of the quality of life collected with EQ-5D
measure: Over all Response Rate
time frame: At week 18
description: Overall response rate according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
arm group label: Standard arm: Trabectedin in monotherapy
arm group type: Active Comparator
description: Trabectedin in monotherapy at the dose 1.5 or 1.3 mg/m2 (according institutional practice) given as intravenous infusion at day 1 every 3 weeks (21 days cycle)
arm group label: Experimental arm: Trabectedin + Olaparib
arm group type: Experimental
description: Trabectedin at the dose 1.1mg/m2 given as intravenous infusion at day 1 every 3 weeks (21 days cycle) plus Olaparib per os at the dose of 150 mg twice a day
intervention type: Drug
intervention name: Standard arm: Trabectedin in monotherapy
description: Trabectedin in monotherapy
arm group label: Standard arm: Trabectedin in monotherapy
other name: Trabectedin arm
intervention type: Drug
intervention name: Experimental arm: Trabectedin + Olaparib
description: Trabectedin given in combination to olaparib
arm group label: Experimental arm: Trabectedin + Olaparib
other name: Trabectedin+ Olaparib arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Giovanni Giovanni, MD
role: Principal Investigator
affiliation: Fondazione del Piemonte IRCCS di Candiolo
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country: Italy
citation: Grignani G, D'Ambrosio L, Pignochino Y, Palmerini E, Zucchetti M, Boccone P, Aliberti S, Stacchiotti S, Bertulli R, Piana R, Miano S, Tolomeo F, Chiabotto G, Sangiolo D, Pisacane A, Dei Tos AP, Novara L, Bartolini A, Marchesi E, D'Incalci M, Bardelli A, Picci P, Ferrari S, Aglietta M. Trabectedin and olaparib in patients with advanced and non-resectable bone and soft-tissue sarcomas (TOMAS): an open-label, phase 1b study from the Italian Sarcoma Group. Lancet Oncol. 2018 Oct;19(10):1360-1371. doi: 10.1016/S1470-2045(18)30438-8. Epub 2018 Sep 11.
PMID: 30217671
citation: Samuels BL, Chawla S, Patel S, von Mehren M, Hamm J, Kaiser PE, Schuetze S, Li J, Aymes A, Demetri GD. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Ann Oncol. 2013 Jun;24(6):1703-9. doi: 10.1093/annonc/mds659. Epub 2013 Feb 5.
PMID: 23385197
citation: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. doi: 10.1016/S1470-2045(16)30376-X. Epub 2016 Sep 9.
PMID: 27617661
citation: Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. Epub 2017 Jul 25. Erratum In: Lancet Oncol. 2017 Sep;18(9):e510.
PMID: 28754483
responsible party type: Sponsor
mesh term: Sarcoma
mesh term: Olaparib
mesh term: Trabectedin
sharing ipd: No