<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/NCT03032406</url>
  </required_header>
  <id_info>
    <org_study_id>UPCC 24116</org_study_id>
    <nct_id>NCT03032406</nct_id>
  </id_info>
  <brief_title>CLEVER Pilot Trial: A Phase II Pilot Trial of HydroxyChLoroquine, EVErolimus or the Combination for Prevention of Recurrent Breast Cancer</brief_title>
  <official_title>CLEVER Pilot Trial: A Phase II Pilot Trial of HydroxyChLoroquine, EVErolimus or the Combination for Prevention of Recurrent Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Abramson Cancer Center at Penn Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Abramson Cancer Center at Penn Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the feasibility of administering HCQ, EVE or the combination in patients who have&#xD;
      completed primary therapy for breast cancer and harbor bone marrow disseminated tumor cells.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 23, 2017</start_date>
  <completion_date type="Anticipated">May 23, 2025</completion_date>
  <primary_completion_date type="Actual">May 17, 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Adverse Events</measure>
    <time_frame>3 years</time_frame>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Breast Cancer Stage IIB</condition>
  <arm_group>
    <arm_group_label>HCQ alone (Arm A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>EVE alone (Arm B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>combination HCQ and EVE (Arm C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>observation (Arm D)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine</intervention_name>
    <description>Hydroxychloroquine</description>
    <arm_group_label>HCQ alone (Arm A)</arm_group_label>
    <arm_group_label>combination HCQ and EVE (Arm C)</arm_group_label>
    <arm_group_label>observation (Arm D)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus</intervention_name>
    <description>Everolimus</description>
    <arm_group_label>EVE alone (Arm B)</arm_group_label>
    <arm_group_label>combination HCQ and EVE (Arm C)</arm_group_label>
    <arm_group_label>observation (Arm D)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically-confirmed, primary, invasive breast cancer diagnosed within 5 years of&#xD;
             study entry.&#xD;
&#xD;
          -  Qualifying risk status, at diagnosis utilizing receptor testing by&#xD;
&#xD;
        ASCO/CAP guidelines, meeting one of the following:&#xD;
&#xD;
          -  Histologically positive axillary lymph nodes&#xD;
&#xD;
          -  Primary tumor that is ER/PR/Her2 negative&#xD;
&#xD;
          -  Primary tumor that is ER+/Her2 negative/Lymph node negative with Breast Cancer&#xD;
             Recurrence Score of ≥ 25 per the Genomic Health Oncotype DX breast cancer test&#xD;
&#xD;
          -  Evidence of residual disease in the breast on pathological assessment after&#xD;
             neoadjuvant chemotherapy.&#xD;
&#xD;
          -  Patients must have completed all primary therapy (definitive surgery, (neo)adjuvant&#xD;
             chemotherapy adjuvant radiation and/or Her2-directed therapy) for the index malignancy&#xD;
             at least 4 weeks prior to study entry. All prior treatment-related toxicity must be&#xD;
             resolved prior to study enrollment. Concurrent receipt of adjuvant endocrine and bone&#xD;
             modifying agents is allowed per standard of care guidelines.&#xD;
&#xD;
          -  Bone marrow aspirate after completion of therapy demonstrates detectable DTCs (via&#xD;
             IHC)&#xD;
&#xD;
          -  No evidence of recurrent local or distant breast cancer by physical examination, blood&#xD;
             tests (CBC, LFTs, Alk Phos), or symptom-directed imaging, per NCCN guidelines.&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  ECOG performance status 2&#xD;
&#xD;
          -  No contraindications to the study medications or uncontrolled medical illness.&#xD;
&#xD;
          -  Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L,&#xD;
             Hb &gt;9 g/dL&#xD;
&#xD;
          -  Adequate liver function as shown by: Serum bilirubin ≤ 1.5 x ULN, ALT and AST ≤ 2.5 x&#xD;
             ULN, and INR ≤1.5&#xD;
&#xD;
          -  Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a&#xD;
             stable dose of anticoagulant for &gt;2 weeks at time of randomization. For patients on&#xD;
             therapeutic anti-coagulants, medication must be clinically held peri-procedure (bone&#xD;
             marrow aspirate) per standard clinical management.&#xD;
&#xD;
          -  Adequate renal function: serum creatinine ≤ 2.0 x ULN or creatinine clearance (CrCl) ≥&#xD;
             30mL/min obtained within 28 days prior to registration. A calculated creatinine&#xD;
             clearance by Cockcroft-Gault Formula is acceptable in lieu of a measured value.&#xD;
&#xD;
          -  Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x&#xD;
             ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only&#xD;
             be included after initiation of appropriate lipid lowering medication.&#xD;
&#xD;
          -  Ability to provide informed consent&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  Concurrent enrollment on another investigational therapy&#xD;
&#xD;
          -  Prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).&#xD;
&#xD;
          -  Known hypersensitivity to Everolimus or other rapamycins (sirolimus, temsirolimus) or&#xD;
             to its excipients.&#xD;
&#xD;
          -  Patients receiving chronic, high dose systemic treatment with corticosteroids defined&#xD;
             as: chronic use of cortisone &gt;50mg; hydrocortisone &gt;40mg, prednisone &gt;10mg,&#xD;
             methylprednisone &gt;8mg or dexamethasone &gt; 1.5mg; or another immunosuppressive agent.&#xD;
             Topical or inhaled corticosteroids are allowed.&#xD;
&#xD;
          -  Patients should not receive immunization with attenuated live vaccines within one week&#xD;
             of study entry or during study period.&#xD;
&#xD;
          -  Patients who have any severe and/or uncontrolled medical conditions or other&#xD;
             conditions that could affect their participation in the study including: Symptomatic&#xD;
             congestive heart failure of New York heart Association Class III or IV Unstable angina&#xD;
             pectoris, myocardial infarction within 6 months of start of study drug, serious&#xD;
             uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease&#xD;
             Severely impaired lung function with a previously documented spirometry and DLCO that&#xD;
             is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest&#xD;
             on room air Uncontrolled diabetes as defined by fasting serum glucose &gt;1.5 x ULN&#xD;
             Active (acute or chronic) or uncontrolled severe infections Liver disease such as&#xD;
             cirrhosis, chronic active hepatitis or chronic persistent hepatitis A known history of&#xD;
             HIV seropositivity as reported by the patient Impairment of gastrointestinal function&#xD;
             or gastrointestinal disease that may significantly alter the absorption of EVE (e.g.,&#xD;
             ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or&#xD;
             small bowel resection) Patients with an active, bleeding diathesis Active or latent,&#xD;
             untreated Hepatitis B or C. A detailed assessment of Hepatitis B/C medical history and&#xD;
             risk factors must be done at screening for all patients. HBV DNA and HCV RNA PCR&#xD;
             testing are required at screening for all patients with a positive medical history&#xD;
             based on risk factors and/or confirmation of prior HBV/HCV infection.&#xD;
&#xD;
          -  Female patients who are pregnant or breast feeding, or adults of reproductive&#xD;
             potential who are not using effective birth control methods. If barrier contraceptives&#xD;
             are being used, these must be continued throughout the trial and for 8 weeks after&#xD;
             stopping study drug, by both sexes. Hormonal contraceptives are not acceptable as a&#xD;
             sole method of contraception. (Women of childbearing potential must have a negative&#xD;
             urine or serum pregnancy test within 7 days prior to administration of EVE.)&#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>Angela DeMichele, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Abramson Cancer Center at Penn Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Abramson Cancer Center of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>July 21, 2023</last_update_submitted>
  <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</mesh_term>
    <mesh_term>Everolimus</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/NCT03032406
org study id: UPCC 24116
nct id: NCT03032406
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
To evaluate the feasibility of administering HCQ, EVE or the combination in patients who have
      completed primary therapy for breast cancer and harbor bone marrow disseminated tumor cells.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Adverse Events
time frame: 3 years
arm group label: HCQ alone (Arm A)
arm group type: Experimental
arm group label: EVE alone (Arm B)
arm group type: Experimental
arm group label: combination HCQ and EVE (Arm C)
arm group type: Experimental
arm group label: observation (Arm D)
arm group type: Experimental
intervention type: Drug
intervention name: Hydroxychloroquine
description: Hydroxychloroquine
arm group label: HCQ alone (Arm A)
arm group label: combination HCQ and EVE (Arm C)
arm group label: observation (Arm D)
intervention type: Drug
intervention name: Everolimus
description: Everolimus
arm group label: EVE alone (Arm B)
arm group label: combination HCQ and EVE (Arm C)
arm group label: observation (Arm D)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Angela DeMichele, MD
role: Principal Investigator
affiliation: Abramson Cancer Center at Penn Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Hydroxychloroquine
mesh term: Everolimus