xml: <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/NCT05997017</url>
    </required_header>
    <id_info>
      <org_study_id>EEC-201</org_study_id>
      <nct_id>NCT05997017</nct_id>
    </id_info>
    <brief_title>Trial of Nab-Sirolimus in Combination With Letrozole in Patients With Advanced or Recurrent Endometrioid Endometrial Cancer</brief_title>
    <official_title>A Phase 2 Multi-center Open-label Trial of Nab-Sirolimus in Combination With Letrozole in Advanced or Recurrent Endometrioid Endometrial Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Aadi Bioscience, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Aadi Bioscience, Inc.</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        A Phase 2 Multi-center Open-label Trial of nab-Sirolimus in Combination with Letrozole in&#xD;
        Advanced or Recurrent Endometrioid Endometrial Cancer&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a prospective phase 2, open-label, multi-institutional study to evaluate the efficacy&#xD;
        and safety of nab-sirolimus + letrozole in patients with advanced or recurrent endometrioid&#xD;
        endometrial carcinoma who have received 0-1 prior lines of chemotherapy in the&#xD;
        recurrent/metastatic setting. Patients will be treated with nab-sirolimus (given IV on Days 1&#xD;
        and 8 in a 21-day cycle, combined with letrozole (orally, daily) until unacceptable toxicity&#xD;
        or disease progression, or until in the opinion of the Investigator the patient is no longer&#xD;
        benefiting from therapy, or at patient discretion.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 2023</start_date>
    <completion_date type="Anticipated">October 2026</completion_date>
    <primary_completion_date type="Anticipated">March 2025</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>Overall response rate (ORR)</measure>
      <time_frame>12 Months</time_frame>
      <description>ORR, defined as the proportion of patients with best overall response (BOR) of confirmed partial response (PR) or complete response (CR) from the time of study treatment initiation until progression of disease (PD) as determined by the Investigator using RECIST v1.1.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Duration of response (DOR)</measure>
      <time_frame>12 Months</time_frame>
      <description>Determined for patients with BOR of confirmed CR or PR</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR): CR or PR</measure>
      <time_frame>12 Months</time_frame>
      <description>BOR of confirmed CR or PR (either of any duration) or stable disease (SD) following study treatment initiation (by IRR)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to response (TTR)</measure>
      <time_frame>12 Months</time_frame>
      <description>Time from study treatment initiation to initial measurement of CR or PR, where CR or PR is subsequently confirmed</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>12 Months</time_frame>
      <description>Number of months from study treatment initiation to the date of disease progression 3 or death due to any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>24 Months</time_frame>
      <description>Number of months from study treatment initiation to the date of death due to any cause or last follow up date if alive</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence and severity</measure>
      <time_frame>12 Months</time_frame>
      <description>Of treatment-emergent and treatment-related adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">29</enrollment>
    <condition>Endometrial Cancer</condition>
    <condition>Endometrioid Tumor</condition>
    <condition>Cancer</condition>
    <condition>Tumor</condition>
    <condition>Recurrent Endometrial Carcinoma</condition>
    <condition>Endometrioid Endometrial Cancer</condition>
    <arm_group>
      <arm_group_label>Endometrioid Endometrial Cancer</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients with advanced or recurrent endometrioid endometrial carcinoma</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>nab-sirolimus</intervention_name>
      <description>Prospective Phase 2, open-label, multi-institutional study to evaluate the efficacy and safety of nab-sirolimus + letrozole in patients</description>
      <arm_group_label>Endometrioid Endometrial Cancer</arm_group_label>
      <other_name>ABI-009</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients must have clinically confirmed advanced or recurrent endometrioid endometrial&#xD;
               carcinoma. Histologic documentation of the recurrence is suggested but not required.&#xD;
  &#xD;
            2. All patients must have 1 or more measurable target lesion at baseline by computed&#xD;
               tomography (CT; or magnetic resonance imaging [MRI] if CT scans are contraindicated)&#xD;
               as defined by RECIST version 1.1.&#xD;
  &#xD;
            3. Patients must have EEC that is metastatic or locally advanced where surgical resection&#xD;
               is not an option or likely to result in severe morbidity.&#xD;
  &#xD;
            4. Prior treatment history:&#xD;
  &#xD;
                 1. Adjuvant setting - treatment with chemotherapy, hormonal therapy,checkpoint&#xD;
                    inhibitors, and/or other therapy is permitted as long as theadjuvant therapy&#xD;
                    ended ≥6 months from enrollment.&#xD;
  &#xD;
                 2. Recurrent/advanced/metastatic setting - treatment with 0-1 prior chemotherapy&#xD;
                    regimens is permitted (patients may be naïve to chemotherapy); chemotherapy must&#xD;
                    have been completed ≥3 months prior to enrollment. Patients are permitted to have&#xD;
                    received adjuvant chemotherapy and no more than 1 line of chemotherapy in the&#xD;
                    recurrent/advanced/metastatic setting.&#xD;
  &#xD;
                 3. Non-chemotherapy-based treatment (eg, checkpoint inhibitors, hormonal therapy,&#xD;
                    and/or small molecule agents) is permitted at any point as long as therapy ended&#xD;
                    ≥4 weeks prior to enrollment.&#xD;
  &#xD;
                 4. Patients who have received prior therapy in the recurrent/advanced/metastatic&#xD;
                    setting must have achieved a complete or partial response(investigator-assessed)&#xD;
                    to at least 1 therapy.&#xD;
  &#xD;
            5. Age: 18 years or older.&#xD;
  &#xD;
            6. Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or&#xD;
               1.&#xD;
  &#xD;
            7. Adequate liver function:&#xD;
  &#xD;
                 1. Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's&#xD;
                    syndrome, then ≤3 × ULN)&#xD;
  &#xD;
                 2. Aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if attributable to liver&#xD;
                    metastases)&#xD;
  &#xD;
            8. Adequate renal function: creatinine clearance (CrCL) ≥30 mL/min based on&#xD;
               Cockcroft-Gault&#xD;
  &#xD;
            9. Adequate hematologic parameters:&#xD;
  &#xD;
                 1. Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factor support allowed)&#xD;
  &#xD;
                 2. Platelet count ≥100,000/mm3 (100 × 109/L) (transfusion and/or growth factor&#xD;
                    support allowed)&#xD;
  &#xD;
                 3. Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)&#xD;
  &#xD;
           10. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be less&#xD;
               than or equal to 350 mg/dL.&#xD;
  &#xD;
           11. Minimum of 4 weeks since any major surgery, completion of radiation, or completion of&#xD;
               prior systemic anticancer therapy, or at least 5 half-lives if the prior therapy is a&#xD;
               single agent small-molecule therapeutic, and adequately recovered from the acute&#xD;
               toxicities of any prior therapy, including neuropathy, to Grade ≤1.&#xD;
  &#xD;
           12. Non-pregnant and non-breastfeeding female:&#xD;
  &#xD;
                 1. Females of childbearing potential must agree to use effective contraception or&#xD;
                    abstinence without interruption from 28 days prior to starting nab-Sirolimus&#xD;
                    through 3 months after the last dose of nab-Sirolimus and have a negative serum&#xD;
                    pregnancy test (beta human chorionic gonadotropin [β-hCG]) result at screening&#xD;
                    and agree to ongoing pregnancy testing during the course of the study, and after&#xD;
                    the end of study treatment. A second form of birth control is required even if&#xD;
                    she has had a tubal ligation.&#xD;
  &#xD;
                 2. Sexual abstinence is considered a highly effective contraceptive method only if&#xD;
                    defined as refraining from heterosexual intercourse from 28 days prior to&#xD;
                    starting study medication throughout 3 months after last dose of study&#xD;
                    medication. The reliability of sexual abstinence should be evaluated in relation&#xD;
                    to the duration of the study and the preferred and usual lifestyle of the&#xD;
                    patient.&#xD;
  &#xD;
           13. The patient understands and signs the informed consent.&#xD;
  &#xD;
           14. Willingness and ability to comply with scheduled visits, laboratory tests, and other&#xD;
               study procedures.&#xD;
  &#xD;
           15. Patients with a known history of human immunodeficiency virus (HIV)infection are&#xD;
               eligible if:&#xD;
  &#xD;
                 1. There has been no acquired immunodeficiency syndrome (AIDS)-defining&#xD;
                    opportunistic infection in 12 months prior to enrollment.&#xD;
  &#xD;
                 2. The patient has been receiving an antiretroviral therapy regimen for≥4 weeks and&#xD;
                    the HIV viral load is &lt;400 copies/mL prior to enrollment.&#xD;
  &#xD;
                 3. Antiretroviral therapy regimen does not include strong cytochrome(CYP)3A4&#xD;
                    inhibitors or inducers&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Prior treatment with an mTOR inhibitor, including nab-sirolimus.&#xD;
  &#xD;
            2. Patients with known inactivating TSC1 or TSC2 alterations (based on tissue or liquid&#xD;
               next generation sequencing [NGS]) unless the PRECISION 1 study (NCT05103358) has been&#xD;
               closed to enrollment.&#xD;
  &#xD;
            3. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective&#xD;
               treatment, either ongoing or completed ≤7 days prior to enrollment.&#xD;
  &#xD;
            4. Patients with primary refractory disease (ie, those who have never achieved a complete&#xD;
               or partial response to prior therapy) are not permitted on study.&#xD;
  &#xD;
            5. Patients with the following are excluded:&#xD;
  &#xD;
                 1. Known or suspected brain metastases.&#xD;
  &#xD;
                 2. Severe heart disease defined as unstable angina pectoris, New York Heart&#xD;
                    Association (NYHA) Class III or IV congestive heart failure, myocardial&#xD;
                    infarction ≤6 months prior to first study treatment, serious uncontrolled cardiac&#xD;
                    arrhythmia or any other clinically significant cardiac disease.&#xD;
  &#xD;
                 3. Severe lung disease defined as a diffusing capacity for carbon monoxide (DLCO)&#xD;
                    that is ≤50% of normal predicted value and/or an O2 saturation ≤88% at rest on&#xD;
                    room air (Note: spirometry and pulmonary function tests [PFTs] are not required&#xD;
                    to be performed unless clinically indicated).&#xD;
  &#xD;
                 4. Nonmalignant medical illnesses that are uncontrolled or whose control may be&#xD;
                    jeopardized by the treatment with the study therapy.&#xD;
  &#xD;
                 5. A history of malignancies other than the one under treatment unless the patient&#xD;
                    is disease-free for more than 5 years from completion of therapy administered&#xD;
                    with curative intent. Controlled non-melanoma skin cancers, carcinoma in situ of&#xD;
                    the cervix, resected incidental prostate cancer, certain low grade hematologic&#xD;
                    malignancies (eg, chronic lymphocytic leukemia [CLL], follicular lymphoma, etc),&#xD;
                    or other adequately treated carcinoma in situ may be eligible, after discussion&#xD;
                    with the Medical Monitor.&#xD;
  &#xD;
                 6. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic&#xD;
                    blood pressure ≥100 mmHg&#xD;
  &#xD;
                 7. Patients with history of interstitial lung disease and/or pneumonitis, or&#xD;
                    pulmonary hypertension.&#xD;
  &#xD;
                 8. Active hepatitis B and/or hepatitis C infection and detectable viral load despite&#xD;
                    antiviral therapy&#xD;
  &#xD;
            6. Required use of concomitant medications with strong CYP3A4 interactions (induction or&#xD;
               inhibition) should be discontinued (strong inhibitors include ketoconazole,&#xD;
               itraconazole, voriconazole, erythromycin, clarithromycin, telithromycin; strong&#xD;
               inducers include rifampin and rifabutin). These agents must be discontinued prior to&#xD;
               first dose of nab-sirolimus.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <gender_based>Yes</gender_based>
      <gender_description>Female</gender_description>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Willis Navarro, MD</last_name>
      <role>Study Director</role>
      <affiliation>Aadi Bioscience</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Aadi Bioscience Medical Information</last_name>
      <phone>1-888-246-2234</phone>
      <email>MedInfo@aadibio.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>University Oklahoma Stephenson Cancer Center</name>
        <address>
          <city>Oklahoma City</city>
          <state>Oklahoma</state>
          <zip>73104</zip>
          <country>United States</country>
        </address>
      </facility>
      <investigator>
        <last_name>Lauren Dockery, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 10, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>nab-Sirolimus</keyword>
    <keyword>FYARRO</keyword>
    <keyword>Letrozole</keyword>
    <keyword>Endometrial</keyword>
    <keyword>Recurrent</keyword>
    <keyword>ABI-009</keyword>
    <keyword>Endometrial Carcinoma</keyword>
    <keyword>Endometrioid Tumor</keyword>
    <keyword>Endometrial Cancer</keyword>
    <keyword>Recurrent Endometrial Carcinoma</keyword>
    <keyword>Endometrioid Endometrial Cancer</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma</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>Sirolimus</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05997017
  org study id: EEC-201
  nct id: NCT05997017
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  A Phase 2 Multi-center Open-label Trial of nab-Sirolimus in Combination with Letrozole in
        Advanced or Recurrent Endometrioid Endometrial Cancer
  This is a prospective phase 2, open-label, multi-institutional study to evaluate the efficacy
        and safety of nab-sirolimus + letrozole in patients with advanced or recurrent endometrioid
        endometrial carcinoma who have received 0-1 prior lines of chemotherapy in the
        recurrent/metastatic setting. Patients will be treated with nab-sirolimus (given IV on Days 1
        and 8 in a 21-day cycle, combined with letrozole (orally, daily) until unacceptable toxicity
        or disease progression, or until in the opinion of the Investigator the patient is no longer
        benefiting from therapy, or at patient discretion.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Overall response rate (ORR)
  time frame: 12 Months
  description: ORR, defined as the proportion of patients with best overall response (BOR) of confirmed partial response (PR) or complete response (CR) from the time of study treatment initiation until progression of disease (PD) as determined by the Investigator using RECIST v1.1.
  measure: Duration of response (DOR)
  time frame: 12 Months
  description: Determined for patients with BOR of confirmed CR or PR
  measure: Disease Control Rate (DCR): CR or PR
  time frame: 12 Months
  description: BOR of confirmed CR or PR (either of any duration) or stable disease (SD) following study treatment initiation (by IRR)
  measure: Time to response (TTR)
  time frame: 12 Months
  description: Time from study treatment initiation to initial measurement of CR or PR, where CR or PR is subsequently confirmed
  measure: Progression-free survival (PFS)
  time frame: 12 Months
  description: Number of months from study treatment initiation to the date of disease progression 3 or death due to any cause
  measure: Overall survival (OS)
  time frame: 24 Months
  description: Number of months from study treatment initiation to the date of death due to any cause or last follow up date if alive
  measure: Incidence and severity
  time frame: 12 Months
  description: Of treatment-emergent and treatment-related adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
  arm group label: Endometrioid Endometrial Cancer
  arm group type: Experimental
  description: Patients with advanced or recurrent endometrioid endometrial carcinoma
  intervention type: Drug
  intervention name: nab-sirolimus
  description: Prospective Phase 2, open-label, multi-institutional study to evaluate the efficacy and safety of nab-sirolimus + letrozole in patients
  arm group label: Endometrioid Endometrial Cancer
  other name: ABI-009
  criteria: 
  gender: All
  gender based: Yes
  gender description: Female
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Willis Navarro, MD
  role: Study Director
  affiliation: Aadi Bioscience
  last name: Aadi Bioscience Medical Information
  phone: 1-888-246-2234
  email: MedInfo@aadibio.com
  facility: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Endometrial Neoplasms
  mesh term: Recurrence
  mesh term: Sirolimus