<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/NCT02188550</url>
  </required_header>
  <id_info>
    <org_study_id>CRAD001CUS242T</org_study_id>
    <nct_id>NCT02188550</nct_id>
  </id_info>
  <brief_title>Single Arm Trial With Combination of Everolimus and Letrozole in Treatment of Platinum Resistant Relapse or Refractory or Persistent Ovarian Cancer/Endometrial Cancer</brief_title>
  <official_title>Phase II Single Arm Trial With Combination of Everolimus and Letrozole in Treatment of Platinum Resistant Relapse or Refractory or Persistent Ovarian Cancer/Endometrial Cancer (CRAD001CUS242T)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sinai Hospital of Baltimore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sinai Hospital of Baltimore</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to determine if the combination of Everolimus and Letrozole is&#xD;
      effective in the treatment of women with either recurrent or persistent epithelial ovarian,&#xD;
      fallopian tube, primary peritoneal or endometrial cancer.&#xD;
&#xD;
      Experiments have shown that everolimus (Afinitor®) can prevent cells such as cancer from&#xD;
      growing in number. Therefore, everolimus (Afinitor®) is being tested in specific diseases to&#xD;
      stop cells from growing too fast (as in cancer).&#xD;
&#xD;
      Everolimus (Afinitor®) has been FDA approved for adults with advanced kidney cancer (Renal&#xD;
      Cell Carcinoma). Everolimus (Afinitor®) received approval for patients with subependymal&#xD;
      giant cell astrocytoma (SEGA), a brain tumor seen with genetic conditions called tuberous&#xD;
      sclerosis complex (TSC) who require therapy, but are not candidates for surgery. Everolimus&#xD;
      (Afinitor®) was approved for pancreatic neuroendocrine tumor (PNET) in patients with&#xD;
      unresectable, locally advanced, or metastatic disease. Everolimus (Afinitor®) received&#xD;
      approval for the treatment of postmenopausal women with advanced hormone receptor-positive,&#xD;
      HER2- negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure&#xD;
      of treatment with letrozole or anastrozole. Everolimus (Afinitor®) also received approval for&#xD;
      the treatment of patients with TSC who have renal angiomyolipoma not requiring immediate&#xD;
      surgery.&#xD;
&#xD;
      Everolimus (Afinitor®) has been used to treat patients in clinical studies since 2002 and&#xD;
      approximately 25,645 patients (as of 30-Sep-2012) have been treated with everolimus&#xD;
      (Afinitor®).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single arm, non-randomized, open-label study with a combination of everolimus and&#xD;
      letrozole once a day dosing . Each cycle would be 28days and patients would be scanned after&#xD;
      every 3 cycles for response, until disease progression is documented.&#xD;
&#xD;
      Subjects will take two pills once a day by mouth with a glass of water.&#xD;
&#xD;
      Before the study…&#xD;
&#xD;
      Subjects will need to have the following exams, tests or procedures to find out if they can&#xD;
      be in the study. These exams, tests or procedures are part of regular cancer care and may be&#xD;
      done even if subjects do not join the study. If subjects have had some of them recently, they&#xD;
      may not need to be repeated. This will be up to your study doctor.&#xD;
&#xD;
        -  Medical history risk and physical examination,&#xD;
&#xD;
        -  Blood tests to measure blood counts, blood mineral levels, and check liver and kidney&#xD;
           function,&#xD;
&#xD;
        -  CT scan or MRI of the abdomen and pelvis to measure detectable tumor&#xD;
&#xD;
        -  A pregnancy blood test if subjects are capable of becoming pregnant&#xD;
&#xD;
        -  Urinalysis (examination of urine)&#xD;
&#xD;
        -  The European Organization for research and treatment of cancer global quality of life&#xD;
           questionnaire C30 (QLQ-C30) -This standard questionnaire helps us to measure quality of&#xD;
           life. This questionnaire will take subjects 15 minutes to complete and will be completed&#xD;
           at entry into the study and at week 12 and 24 during the study.&#xD;
&#xD;
      Tests will be done for hepatitis B and/or C if:&#xD;
&#xD;
        -  Subjects have a risk of having hepatitis B and/or C or if subjects live or have lived in&#xD;
           specific geographical areas, such as Asia, Africa, Central and South America, Eastern&#xD;
           Europe and Spain, Portugal or Greece;&#xD;
&#xD;
        -  The study doctor thinks it is appropriate.&#xD;
&#xD;
      Subjects that have positive hepatitis B or hepatitis C results at screening may be required&#xD;
      to take medication for up to 2 weeks before they start everolimus (Afinitor®) treatment.&#xD;
&#xD;
      During the Study…&#xD;
&#xD;
      If the exams, tests and procedures show that subjects can be in the study, and they choose to&#xD;
      take part, then they will need the following tests and procedures. They are part of regular&#xD;
      cancer care.&#xD;
&#xD;
        -  History and physical examination&#xD;
&#xD;
        -  Weekly blood tests to measure blood counts, blood mineral levels, blood clotting and&#xD;
           check liver and kidney function&#xD;
&#xD;
        -  Evaluation of side effects subjects may experience from the study treatment&#xD;
&#xD;
        -  Tests to having hepatitis B and/or C&#xD;
&#xD;
        -  CT scan or MRI of the abdomen and pelvis every 12 weeks&#xD;
&#xD;
        -  The European Organization for research and treatment of cancer global quality of life&#xD;
           questionnaire C30 (QLQ-C30)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>June 2014</start_date>
  <primary_completion_date type="Anticipated">June 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Tumor Response to treatment with Everolimus and Letrozole using RECIST Criteria</measure>
    <time_frame>Baseline, Then every 12 weeks while on Everolimus and Letrozole up to 36 months</time_frame>
    <description>The duration of response will be documented and also compared to the duration of response ot the last, most recent, cancer treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival of patients treated with the combination of letrozole and everolimus</measure>
    <time_frame>From randomization until date of death, assessed up to 36 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Ovarian Cancer</condition>
  <condition>Endometrial Cancer</condition>
  <arm_group>
    <arm_group_label>Single</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This is a single arm, non-randomized, open-label study with a combination of everolimus and letrozole once a day dosing . Each cycle would be 28days and patients would be scanned after every 3 cycles for response, until disease progression is documented</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>everolimus and letrozole</intervention_name>
    <description>This is a single arm, non-randomized, open-label study with a combination of everolimus and letrozole once a day dosing . Each cycle would be 28days and patients would be scanned after every 3 cycles for response, until disease progression is documented&#xD;
The duration of the study will be until disease progression&#xD;
Everolimus and Letrozole will be administered as noted below;&#xD;
6.1.1 Dosing regimen&#xD;
Dosage : Everolimus Dose: 10 Unit: mg Frequency: daily Route of administration: Orally Dosage : Letrozole Dose: 2.5 Unit: mg Frequency: daily Route of administration: Orally</description>
    <arm_group_label>Single</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Post-menopausal or post-oophorectomy.&#xD;
&#xD;
          -  Performance status Less than or equal to ECOG 2&#xD;
&#xD;
          -  Patients must have relapse or refractory or persistent epithelial ovarian, fallopian&#xD;
             tube, primary peritoneal carcinoma or endometrial cancer. Histologic documentation of&#xD;
             the original primary tumor is required via pathology report.&#xD;
&#xD;
          -  Patients must have received treatment with a platinum-based chemotherapeutic regimen&#xD;
             for management of primary disease containing carboplatin, cisplatin. This initial&#xD;
             treatment may have included intraperitoneal therapy, consolidation, noncytotoxic&#xD;
             agents (biologic/targeted therapy) or extended therapy administered after surgical or&#xD;
             non-surgical assessment.&#xD;
&#xD;
          -  Patients must have platinum-resistant disease, defined as progression &lt; 12 months&#xD;
             after completion of first-or-second-line platinum based chemotherapy. The date&#xD;
             (platinum-free interval) should be calculated from the last administered dose of&#xD;
             platinum therapy.&#xD;
&#xD;
          -  Platinum sensitive patients must have progressed/relapsed after receiving a second&#xD;
             line platinum therapy.&#xD;
&#xD;
          -  Patients with platinum-refractory primary disease, defined as having disease3&#xD;
             progression while receiving first-line platinum-based chemotherapy.&#xD;
&#xD;
          -  Patients are allowed to receive, but are not required to receive, one additional&#xD;
             cytotoxic regimen for management of relapse or refractory or persistent disease.&#xD;
&#xD;
          -  Patients are allowed to have received, but are not required to have received,&#xD;
             biologic/targeted therapy (e.g., bevacizumab and/or PARP inhibitor) as part of their&#xD;
             primary treatment regimen or for management of relapse or refractory or persistent&#xD;
             disease.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients currently receiving anticancer therapies or who have received anticancer&#xD;
             therapies within 4 weeks of the start of Everolimus (including chemotherapy, antibody&#xD;
             based therapy, etc.); radiation therapy within 2 weeks.&#xD;
&#xD;
          -  Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g.&#xD;
&#xD;
        sirolimus, temsirolimus) or to Letrozole.&#xD;
&#xD;
          -  Known impairment of gastrointestinal (GI) function or GI disease that may&#xD;
             significantly alter the absorption of oral Everolimus;&#xD;
&#xD;
          -  Patients who have any severe and/or uncontrolled medical conditions such as:&#xD;
&#xD;
               1. unstable angina pectoris, symptomatic congestive heart failure, myocardial&#xD;
                  infarction ≤6 months prior to start of Everolimus, serious uncontrolled cardiac&#xD;
                  arrhythmia, or any other clinically significant cardiac disease&#xD;
&#xD;
               2. Symptomatic congestive heart failure of New York heart Association Class III or&#xD;
                  IV&#xD;
&#xD;
               3. active (acute or chronic) or uncontrolled severe infection, liver disease such as&#xD;
                  cirrhosis, decompensated liver disease, and active or chronic hepatitis (i.e.&#xD;
                  quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA),&#xD;
&#xD;
               4. known severely impaired lung function (spirometry and DLCO 50% or less of normal&#xD;
                  and O2 saturation 88% or less at rest on room air),&#xD;
&#xD;
               5. active, bleeding diathesis;&#xD;
&#xD;
          -  Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or&#xD;
             inhaled corticosteroids are allowed;&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sinai Hospital of Baltimore, Inc.</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Judy Bosley, BSN, RN</last_name>
      <phone>410-601-6120</phone>
      <email>jbosley@lifebridgehealth.org</email>
    </contact>
    <contact_backup>
      <last_name>Melissa Loomis</last_name>
      <phone>410-601-6120</phone>
      <email>mloomis@lifebridgehealth.org</email>
    </contact_backup>
    <investigator>
      <last_name>Kenneth Miller, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>May 9, 2014</study_first_submitted>
  <study_first_submitted_qc>July 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>May 18, 2015</last_update_submitted>
  <last_update_submitted_qc>May 18, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 19, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sinai Hospital of Baltimore</investigator_affiliation>
    <investigator_full_name>Kenneth Miller, M.D.</investigator_full_name>
    <investigator_title>Medical Oncologist</investigator_title>
  </responsible_party>
  <keyword>relapse or refractory or persistent epithelial ovarian fallopian tube</keyword>
  <keyword>primary peritoneal carcinoma or endometrial cancer</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>
    <mesh_term>Endometrial Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Everolimus</mesh_term>
    <mesh_term>Letrozole</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02188550
org study id: CRAD001CUS242T
nct id: NCT02188550
lead sponsor: 
has dmc: No
The purpose of the study is to determine if the combination of Everolimus and Letrozole is
      effective in the treatment of women with either recurrent or persistent epithelial ovarian,
      fallopian tube, primary peritoneal or endometrial cancer.

      Experiments have shown that everolimus (Afinitor®) can prevent cells such as cancer from
      growing in number. Therefore, everolimus (Afinitor®) is being tested in specific diseases to
      stop cells from growing too fast (as in cancer).

      Everolimus (Afinitor®) has been FDA approved for adults with advanced kidney cancer (Renal
      Cell Carcinoma). Everolimus (Afinitor®) received approval for patients with subependymal
      giant cell astrocytoma (SEGA), a brain tumor seen with genetic conditions called tuberous
      sclerosis complex (TSC) who require therapy, but are not candidates for surgery. Everolimus
      (Afinitor®) was approved for pancreatic neuroendocrine tumor (PNET) in patients with
      unresectable, locally advanced, or metastatic disease. Everolimus (Afinitor®) received
      approval for the treatment of postmenopausal women with advanced hormone receptor-positive,
      HER2- negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure
      of treatment with letrozole or anastrozole. Everolimus (Afinitor®) also received approval for
      the treatment of patients with TSC who have renal angiomyolipoma not requiring immediate
      surgery.

      Everolimus (Afinitor®) has been used to treat patients in clinical studies since 2002 and
      approximately 25,645 patients (as of 30-Sep-2012) have been treated with everolimus
      (Afinitor®).
This is a single arm, non-randomized, open-label study with a combination of everolimus and
      letrozole once a day dosing . Each cycle would be 28days and patients would be scanned after
      every 3 cycles for response, until disease progression is documented.

      Subjects will take two pills once a day by mouth with a glass of water.

      Before the study…

      Subjects will need to have the following exams, tests or procedures to find out if they can
      be in the study. These exams, tests or procedures are part of regular cancer care and may be
      done even if subjects do not join the study. If subjects have had some of them recently, they
      may not need to be repeated. This will be up to your study doctor.

        -  Medical history risk and physical examination,

        -  Blood tests to measure blood counts, blood mineral levels, and check liver and kidney
           function,

        -  CT scan or MRI of the abdomen and pelvis to measure detectable tumor

        -  A pregnancy blood test if subjects are capable of becoming pregnant

        -  Urinalysis (examination of urine)

        -  The European Organization for research and treatment of cancer global quality of life
           questionnaire C30 (QLQ-C30) -This standard questionnaire helps us to measure quality of
           life. This questionnaire will take subjects 15 minutes to complete and will be completed
           at entry into the study and at week 12 and 24 during the study.

      Tests will be done for hepatitis B and/or C if:

        -  Subjects have a risk of having hepatitis B and/or C or if subjects live or have lived in
           specific geographical areas, such as Asia, Africa, Central and South America, Eastern
           Europe and Spain, Portugal or Greece;

        -  The study doctor thinks it is appropriate.

      Subjects that have positive hepatitis B or hepatitis C results at screening may be required
      to take medication for up to 2 weeks before they start everolimus (Afinitor®) treatment.

      During the Study…

      If the exams, tests and procedures show that subjects can be in the study, and they choose to
      take part, then they will need the following tests and procedures. They are part of regular
      cancer care.

        -  History and physical examination

        -  Weekly blood tests to measure blood counts, blood mineral levels, blood clotting and
           check liver and kidney function

        -  Evaluation of side effects subjects may experience from the study treatment

        -  Tests to having hepatitis B and/or C

        -  CT scan or MRI of the abdomen and pelvis every 12 weeks

        -  The European Organization for research and treatment of cancer global quality of life
           questionnaire C30 (QLQ-C30)
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Tumor Response to treatment with Everolimus and Letrozole using RECIST Criteria
time frame: Baseline, Then every 12 weeks while on Everolimus and Letrozole up to 36 months
description: The duration of response will be documented and also compared to the duration of response ot the last, most recent, cancer treatment.
measure: Overall survival of patients treated with the combination of letrozole and everolimus
time frame: From randomization until date of death, assessed up to 36 months
arm group label: Single
arm group type: Experimental
description: This is a single arm, non-randomized, open-label study with a combination of everolimus and letrozole once a day dosing . Each cycle would be 28days and patients would be scanned after every 3 cycles for response, until disease progression is documented
intervention type: Drug
intervention name: everolimus and letrozole
description: This is a single arm, non-randomized, open-label study with a combination of everolimus and letrozole once a day dosing . Each cycle would be 28days and patients would be scanned after every 3 cycles for response, until disease progression is documented
The duration of the study will be until disease progression
Everolimus and Letrozole will be administered as noted below;
6.1.1 Dosing regimen
Dosage : Everolimus Dose: 10 Unit: mg Frequency: daily Route of administration: Orally Dosage : Letrozole Dose: 2.5 Unit: mg Frequency: daily Route of administration: Orally
arm group label: Single
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Sinai Hospital of Baltimore
investigator full name: Kenneth Miller, M.D.
investigator title: Medical Oncologist
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Endometrial Neoplasms
mesh term: Recurrence
mesh term: Everolimus
mesh term: Letrozole