<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/NCT04421547</url>
  </required_header>
  <id_info>
    <org_study_id>MITO32</org_study_id>
    <nct_id>NCT04421547</nct_id>
  </id_info>
  <brief_title>Efficacy of Letrozole in Recurrent Ovarian Cancer</brief_title>
  <acronym>MITO32</acronym>
  <official_title>PHASE III RANDOMIZED CONTROL CASE STUDY OF LETROZOLE IN WOMEN WITH HEAVILY PRETREATED OVARIAN CANCER (MITO 32)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</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>
      Randomized phase III multicenter study investigating the role of letrozole in heavily&#xD;
      pretreated recurrent ovarian cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, open-label, phase III, multicenter, global study evaluating the&#xD;
      efficacy and safety of Letrozole in heavily pretreated recurrent ovarian cancer patients in&#xD;
      comparison to physician' choice chemotherapy.&#xD;
&#xD;
      Subjects who meet all the inclusion criteria and none of the exclusion criteria will be&#xD;
      randomized in a 1:1 ratio to one of the two arms, as follow:&#xD;
&#xD;
      Arm A: Letrozole 1 tablet (2,5 mg) orally once a day in 28-day cycles Arm B: Pegylated&#xD;
      Liposomal Doxorubicin 40 mg/m2 d1q28 or Topotecan 4 mg/m2 d1,8,15q28 or Gemcitabine 1000&#xD;
      mg/m2 d1,8,15q28 or Paclitaxel 80 mg/m2 d1,8,15q28 In case of objective response and&#xD;
      acceptable toxicity, no maximum number of cycles of treatment is defined.&#xD;
&#xD;
      The aim of the study is to assess the activity of Letrozole in women with recurrent&#xD;
      epithelial ovarian cancer, heavily pretreated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 1, 2020</start_date>
  <completion_date type="Anticipated">December 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2022</primary_completion_date>
  <phase>Phase 3</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>This is a two arms, prospective, open-label multi center randomized phase III study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patient alive at 12 months</measure>
    <time_frame>30 months</time_frame>
    <description>Evaluate the difference in terms of proportion of survivals at 12 months between the two arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>30 months</time_frame>
    <description>Progression Free Survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>30 months</time_frame>
    <description>Overall Survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR</measure>
    <time_frame>30 months</time_frame>
    <description>Objective Response Rate (according to RECIST criteria version 1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TPST</measure>
    <time_frame>30 months</time_frame>
    <description>Time from randomization to the start of the primary subsequent therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TSST</measure>
    <time_frame>30 months</time_frame>
    <description>Time from randomization to the start of the secondary subsequent therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity profile evaluated according to NCI-CTCAE version 5.0</measure>
    <time_frame>30 months</time_frame>
    <description>Toxicity profile (evaluated according to NCI-CTCAE version 5.0)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QoL</measure>
    <time_frame>30 months</time_frame>
    <description>Quality of Life (evaluated by EORTC QLQ-C30/ QLQ-OV28 questionnaire)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">236</enrollment>
  <condition>Epithelial Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>Letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Letrozole 1 tablet (2,5 mg) orally once a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Either Paclitaxel 80 mg/m2 as a 1-h infusion, on days 1,8,15,22 every 28 days or Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 given every 4 weeks or Topotecan 4mg/m2 IV on days 1,8,15 every 4 weeks or Gemcitabine 1000 mg/m2 IV over 30 min on days 1,8,15 every 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole 2.5mg</intervention_name>
    <description>This study will investigate the role of Letrozole in patients affected by heavily pretreated platinum resistant ovarian cancer, compared to standard treatment.</description>
    <arm_group_label>Letrozole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard single agent chemotherapy</intervention_name>
    <description>Either Paclitaxel 80 mg/m2 as a 1-h infusion, on days 1,8,15,22 every 28 days or Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 given every 4 weeks or Topotecan 4mg/m2 IV on days 1,8,15 every 4 weeks or Gemcitabine 1000 mg/m2 IV over 30 min on days 1,8,15 every 28 days.</description>
    <arm_group_label>Standard Chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female of 18 years of age or older&#xD;
&#xD;
          -  Histologically or cytologically documented invasive epithelial ovarian cancer, primary&#xD;
             peritoneal carcinoma, or fallopian tube cancer&#xD;
&#xD;
          -  Platinum resistant or refractory disease (patients who did not respond to last&#xD;
             platinumbased therapy or with last relapse occurred &lt; 6 months from the last dose of&#xD;
             platinum) or patients not amenable of platinum treatment&#xD;
&#xD;
          -  &gt;3 previous chemotherapy lines&#xD;
&#xD;
          -  ECOG performance status 0 -2&#xD;
&#xD;
          -  Measurable and evaluable disease according to RECIST criteria confirmed by&#xD;
             radiological imaging: at least one lesion of ≥ 1.0 cm for non-lymph nodes or ≥ 1.5 cm&#xD;
             in short-axis diameter for lymph nodes at CT scan (Subjects with isolated rising&#xD;
             CA-125 without radiologically visible disease are excluded)&#xD;
&#xD;
          -  Left Ventricular Ejection Fraction (LVEF) ≥ institutional lower limit normal&#xD;
&#xD;
          -  Estimated life expectancy ≥ 16 weeks&#xD;
&#xD;
          -  Adequate functions evidenced by:&#xD;
&#xD;
               -  Hemoglobin ³10.0 g/dl&#xD;
&#xD;
               -  Absolute neutrophil count ³1.5 x 109/L&#xD;
&#xD;
               -  White blood cells &gt;3x109/L&#xD;
&#xD;
               -  Platelet &gt;100 x109/L&#xD;
&#xD;
               -  AST and ALT £ 2.5 x Upper limit of normal, unless liver metastasis, in which case&#xD;
                  AST and ALT &lt; or = 5 x Upper limit of normal will be accepted&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 times the upper limit of normal (ULN)&#xD;
&#xD;
               -  Estimated glomerular filtration ³ 60mL/min using the Cockcroft-Gault equation.&#xD;
&#xD;
          -  Patient able to comply with the treatment&#xD;
&#xD;
          -  Evidence of not pregnancy status as documented by a negative beta-human chorionic&#xD;
             gonadotropin (ß-hCG) test&#xD;
&#xD;
          -  Not breastfeeding women&#xD;
&#xD;
          -  Patients with child-bearing potential using (or willing to use) effective&#xD;
             contraception during treatment and 3 months ahead unless they are postmenopausal (at&#xD;
             least 12 months consecutive amenorrhea, in the appropriate age group and without other&#xD;
             known or suspected cause), or have been sterilized surgically.&#xD;
&#xD;
          -  Comprehension and signature of the informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with borderline ovarian cancer&#xD;
&#xD;
          -  Subject with low malignant potential tumors&#xD;
&#xD;
          -  Less than 3 lines of previous therapies&#xD;
&#xD;
          -  Platinum sensitive disease (last relapse occurred &gt; 6 months from the last dose of&#xD;
             platinum)&#xD;
&#xD;
          -  Less than 4 weeks from last dose of therapy with any investigational agent, or&#xD;
             chemotherapy&#xD;
&#xD;
          -  History of another neoplastic disease (except basal cell carcinoma or cervical&#xD;
             carcinoma in situ adequately treated) unless in remission for 3 years or longer&#xD;
&#xD;
          -  Breastfeeding women&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Prior therapy with letrozole.&#xD;
&#xD;
          -  Severe osteoporosis documented by BMD (Bone Mineral Density) T-score ≤ -2.5 with&#xD;
             existing fragility fracture(s)&#xD;
&#xD;
          -  Patients with a known hypersensitivity to Paclitaxel , PLD, Topotecan, Gemcitabine or&#xD;
             Letrozole or any case of severe toxicity related to them. Also Patients with a known&#xD;
             hypersensitivity to any of the ingredients or excipients of the IMPs (e.g.&#xD;
             macrogolglycerol ricinoleate (polyoxyl castor oil), ethanol, anhydrous, citric acid,&#xD;
             anhydrous, sodium chloride hydrochloric acid, mannitol, sodium acetate, sodium&#xD;
             hydroxide, tartaric acid, lactose monohydrate, maize starch, hypromellose Type 2910,&#xD;
             cellulose microcrystalline, sodium starch glycolate type A, colloidal anhydrous&#xD;
             silica, magnesium stearate, hypromellose 6 cp E464, titanium dioxide E171, Iron oxide&#xD;
             yellow E172, Macrogol 400, talc E553b)&#xD;
&#xD;
          -  Prior resistance to Paclitaxel, PLD, Topotecan, Gemcitabine&#xD;
&#xD;
          -  Patients with active hepatic disease (HCV or HBV infections), hepatic severe&#xD;
             impairment or cirrhosis&#xD;
&#xD;
          -  Bowel obstruction, sub-occlusive disease, prior gastrectomy, symptomatic brain&#xD;
             metastases.&#xD;
&#xD;
          -  Myocardial infarct within six months before enrolment , NYHA Class II or worse heart&#xD;
             failure, unstable angina, serious cardiac arrhythmia or cardiac arrhythmia requiring&#xD;
             treatment.&#xD;
&#xD;
          -  Any serious concomitant illness requiring treatment&#xD;
&#xD;
          -  Pre-existing peripheral neuropathy &gt; CTCAE Grade 2.&#xD;
&#xD;
          -  Concomitant use of strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole,&#xD;
             voriconazole, ritonavir, clarithromycin, and telithromycin) or strong CYP2A6&#xD;
             inhibitors (e.g. methoxsalen) because they may increase exposure to letrozole.&#xD;
&#xD;
          -  Concomitant use of inducers of CYP3A4 (e.g. phenytoin, rifampicin, carbamazepine,&#xD;
             phenobarbital, and St. John's Wort) which may reduce exposure to letrozole.&#xD;
&#xD;
          -  Concomitant use of medicinal products with a narrow therapeutic index that are&#xD;
             substrates for CYP2C19 (e.g. phenytoin, clopidrogel) that may have their systemic&#xD;
             serum concentrations altered by letrozole.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Claudia Marchetti</last_name>
    <phone>+390630158556</phone>
    <email>claudia.marchetti@policlinicogemelli.it</email>
  </overall_contact>
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  <reference>
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    <PMID>15248931</PMID>
  </reference>
  <reference>
    <citation>Stiggelbout AM, de Haes JC. Patient preference for cancer therapy: an overview of measurement approaches. J Clin Oncol. 2001 Jan 1;19(1):220-30. doi: 10.1200/JCO.2001.19.1.220.</citation>
    <PMID>11134216</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 4, 2020</last_update_submitted>
  <last_update_submitted_qc>June 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</investigator_affiliation>
    <investigator_full_name>Claudia Marchetti</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>epithelial ovarian cancer</keyword>
  <keyword>Letrozole</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Letrozole</mesh_term>
  </intervention_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/NCT04421547
org study id: MITO32
nct id: NCT04421547
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Randomized phase III multicenter study investigating the role of letrozole in heavily
      pretreated recurrent ovarian cancer.
This is a randomized, open-label, phase III, multicenter, global study evaluating the
      efficacy and safety of Letrozole in heavily pretreated recurrent ovarian cancer patients in
      comparison to physician' choice chemotherapy.

      Subjects who meet all the inclusion criteria and none of the exclusion criteria will be
      randomized in a 1:1 ratio to one of the two arms, as follow:

      Arm A: Letrozole 1 tablet (2,5 mg) orally once a day in 28-day cycles Arm B: Pegylated
      Liposomal Doxorubicin 40 mg/m2 d1q28 or Topotecan 4 mg/m2 d1,8,15q28 or Gemcitabine 1000
      mg/m2 d1,8,15q28 or Paclitaxel 80 mg/m2 d1,8,15q28 In case of objective response and
      acceptable toxicity, no maximum number of cycles of treatment is defined.

      The aim of the study is to assess the activity of Letrozole in women with recurrent
      epithelial ovarian cancer, heavily pretreated.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a two arms, prospective, open-label multi center randomized phase III study.
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patient alive at 12 months
time frame: 30 months
description: Evaluate the difference in terms of proportion of survivals at 12 months between the two arms.
measure: PFS
time frame: 30 months
description: Progression Free Survival
measure: OS
time frame: 30 months
description: Overall Survival
measure: ORR
time frame: 30 months
description: Objective Response Rate (according to RECIST criteria version 1.1)
measure: TPST
time frame: 30 months
description: Time from randomization to the start of the primary subsequent therapy
measure: TSST
time frame: 30 months
description: Time from randomization to the start of the secondary subsequent therapy
measure: Toxicity profile evaluated according to NCI-CTCAE version 5.0
time frame: 30 months
description: Toxicity profile (evaluated according to NCI-CTCAE version 5.0)
measure: QoL
time frame: 30 months
description: Quality of Life (evaluated by EORTC QLQ-C30/ QLQ-OV28 questionnaire)
arm group label: Letrozole
arm group type: Experimental
description: Letrozole 1 tablet (2,5 mg) orally once a day
arm group label: Standard Chemotherapy
arm group type: Active Comparator
description: Either Paclitaxel 80 mg/m2 as a 1-h infusion, on days 1,8,15,22 every 28 days or Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 given every 4 weeks or Topotecan 4mg/m2 IV on days 1,8,15 every 4 weeks or Gemcitabine 1000 mg/m2 IV over 30 min on days 1,8,15 every 28 days.
intervention type: Drug
intervention name: Letrozole 2.5mg
description: This study will investigate the role of Letrozole in patients affected by heavily pretreated platinum resistant ovarian cancer, compared to standard treatment.
arm group label: Letrozole
intervention type: Drug
intervention name: Standard single agent chemotherapy
description: Either Paclitaxel 80 mg/m2 as a 1-h infusion, on days 1,8,15,22 every 28 days or Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 given every 4 weeks or Topotecan 4mg/m2 IV on days 1,8,15 every 4 weeks or Gemcitabine 1000 mg/m2 IV over 30 min on days 1,8,15 every 28 days.
arm group label: Standard Chemotherapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Claudia Marchetti
phone: +390630158556
email: claudia.marchetti@policlinicogemelli.it
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PMID: 15248931
citation: Stiggelbout AM, de Haes JC. Patient preference for cancer therapy: an overview of measurement approaches. J Clin Oncol. 2001 Jan 1;19(1):220-30. doi: 10.1200/JCO.2001.19.1.220.
PMID: 11134216
responsible party type: Principal Investigator
investigator affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
investigator full name: Claudia Marchetti
investigator title: Principal Investigator
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Letrozole
sharing ipd: Undecided