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/NCT05997056</url>
    </required_header>
    <id_info>
      <org_study_id>NET-202</org_study_id>
      <nct_id>NCT05997056</nct_id>
    </id_info>
    <brief_title>Trial of Nab-sirolimus in Patients With Well-differentiated Neuroendocrine Tumors (NETs) of the Gastrointestinal Tract, Lung, or Pancreas Who Have Not Received Prior Treatment With mTOR Inhibitors</brief_title>
    <official_title>A Phase 2 Multi-center, Open-label, Single Arm Study of Nab-sirolimus in Patients With Well-differentiated Neuroendocrine Tumors (NETs) of the Gastrointestinal Tract, Lung, or Pancreas Who Have Not Received Prior Treatment With mTOR Inhibitors</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        A Phase 2 multi-center, open-label, single arm study of nab-sirolimus in patients with&#xD;
        well-differentiated neuroendocrine tumors (NETs) of the gastrointestinal tract, lung, or&#xD;
        pancreas who have not received prior treatment with mTOR inhibitors&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a prospective phase 2 single arm, open-label, multi-institutional study to determine&#xD;
        the efficacy and safety prospective of nab-sirolimus and patients with functional or&#xD;
        non-functional, well-differentiated, locally advanced unresectable in metastatic NETs of the&#xD;
        GI tract, lung, or pancreas.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 30, 2023</start_date>
    <completion_date type="Anticipated">December 8, 2025</completion_date>
    <primary_completion_date type="Anticipated">May 9, 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>Efficacy of nab-sirolimus</measure>
      <time_frame>12 Months</time_frame>
      <description>Objective Response Rate (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>Incidence and severity of treatment</measure>
      <time_frame>12 Months</time_frame>
      <description>Incidence and severity of treatment-emergent and treatment-related adverse events (AEs) as assessed by NCI CTCAE v5.0</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response</measure>
      <time_frame>12 Months</time_frame>
      <description>Determined for patients with BOR of confirmed CR or PR defined as time from scan first showing response by RECIST v1.1 to PD or death</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate</measure>
      <time_frame>12 Months</time_frame>
      <description>BOR of confirmed CR or PR (either of any duration) or stable disease (SD) ≥12 weeks by RECISTv1.1 following study treatment initiation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to response</measure>
      <time_frame>12 Months</time_frame>
      <description>Time from first dose of study medication to initial measurement of CR or PR, where CR or PR is subsequently confirmed by RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival</measure>
      <time_frame>12 Months</time_frame>
      <description>Number of months from study treatment initiation to the date of disease progression or death due to any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>24 Months</time_frame>
      <description>Number of months from study treatment initiation to the date of death due to any cause</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">21</enrollment>
    <condition>Neuroendocrine Tumors</condition>
    <condition>NET</condition>
    <condition>Pancreatic Neuroendocrine Tumor</condition>
    <condition>Gastrointestinal Neuroendocrine Tumor</condition>
    <condition>Pulmonary Neuroendocrine Tumor</condition>
    <arm_group>
      <arm_group_label>neuroendocrine tumors</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients with well-differentiated neuroendocrine tumors of the gastrointestinal tract, lung, or pancreas.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>nab-sirolimus</intervention_name>
      <description>Prospective phase 2 single arm, open-label, multi-institutional study to determine the efficacy and safety prospective of nab-sirolimus administered by IV infusion</description>
      <arm_group_label>neuroendocrine tumors</arm_group_label>
      <other_name>ABI-009</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients with functional or non-functional, well-differentiated, locally advanced&#xD;
               unresectable or metastatic NETs of the GI tract, lung, or pancreas who have received 2&#xD;
               or less prior lines of therapy excluding somatostatin analogs&#xD;
  &#xD;
            2. Patients with functional NETs may enroll if:&#xD;
  &#xD;
                 1. the patient has been on a stable dose of an somatostatin analogs for ≥12 weeks&#xD;
                    and&#xD;
  &#xD;
                 2. the patient has experienced disease progression while on stable somatostatin&#xD;
                    analogs dose&#xD;
  &#xD;
            3. Patients must have 1 or more measurable target lesions by RECIST v1.1&#xD;
  &#xD;
            4. Age: 18 years or older&#xD;
  &#xD;
            5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or Karnofsky&#xD;
               Performance Status (KPS) ≥80&#xD;
  &#xD;
            6. Adequate liver function:&#xD;
  &#xD;
                 1. Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's&#xD;
                    syndrome or attributable to liver metastases, then ≤3 × ULN)&#xD;
  &#xD;
                 2. Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤2.5 × ULN (≤5 ×&#xD;
                    ULN if attributable to liver metastases)&#xD;
  &#xD;
            7. Adequate renal function: creatinine clearance ≥30 mL/min, Cockcroft-Gault creatinine&#xD;
               clearance = ((140-age) × weight[kg]) / (72 × serum creatinine [mL/min]) × 0.85, if&#xD;
               female.&#xD;
  &#xD;
            8. Adequate hematologic parameters:&#xD;
  &#xD;
                 1. Absolute neutrophil count (ANC) ≥1.0 × 10^9/L (growth factor support allowed)&#xD;
  &#xD;
                 2. Platelet count ≥100,000/mm^3 (100 × 10^9/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;
            9. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be less&#xD;
               than or equal to 350 mg/dL&#xD;
  &#xD;
           10. Minimum of 4 weeks since any major surgery, completion of radiation, and adequately&#xD;
               recovered from the acute toxicities of any prior therapy, including neuropathy, to&#xD;
               Grade ≤1&#xD;
  &#xD;
           11. Male or 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 study medication&#xD;
                    throughout 3 months after last dose of study medication 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 EOS treatment. A second form of birth control is required even if she has had&#xD;
                    a tubal ligation.&#xD;
  &#xD;
                 2. Male patients must agree not to donate sperm and must practice abstinence or&#xD;
                    agree to use a condom during sexual contact with a pregnant female or a female of&#xD;
                    childbearing potential while participating in the study and throughout 3 months&#xD;
                    after last dose of study medication. A second form of birth control is required&#xD;
                    even if he has undergone a successful vasectomy.&#xD;
  &#xD;
                 3. 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;
           12. The patient or the patient's legal guardian(s) understand(s) and sign(s) the informed&#xD;
               consent&#xD;
  &#xD;
           13. Willingness and ability to comply with scheduled visits, laboratory tests, and other&#xD;
               study procedures&#xD;
  &#xD;
           14. 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 mTOR inhibitors including nab-sirolimus&#xD;
  &#xD;
               Note: Patients who have previously received locoregional or liver-directed therapies&#xD;
               (radiofrequency or microwave ablation, transarterial chemoembolization, etc.) are&#xD;
               eligible to enroll in the study.&#xD;
  &#xD;
            2. Patients with functional NETs who are experiencing uncontrolled symptoms attributed to&#xD;
               hormones and other vasoactive substances secreted by the tumor&#xD;
  &#xD;
            3. Patients with inactivating TSC1 or TSC2 alterations (based on tissue or liquid NGS)&#xD;
  &#xD;
            4. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective&#xD;
               treatment, either ongoing or completed ≤7 days prior to enrollment&#xD;
  &#xD;
            5. Patients who have any severe and/or uncontrolled medical or psychiatric conditions or&#xD;
               other conditions that could affect their participation including:&#xD;
  &#xD;
                 1. Known or suspected brain metastases&#xD;
  &#xD;
                 2. Severe heart disease defined as unstable angina pectoris, NYHA Class III or IV&#xD;
                    congestive heart failure, myocardial infarction ≤6 months prior to first study&#xD;
                    treatment, serious uncontrolled cardiac arrhythmia or any other clinically&#xD;
                    significant cardiac disease.&#xD;
  &#xD;
                 3. Severe lung disease defined as a diffusing capacity for carbon monoxide that is&#xD;
                    ≤50% of normal predicted value and/or an O2 saturation ≤88% at rest on room air&#xD;
  &#xD;
                    (Note: Spirometry and pulmonary function tests are not required to be performed&#xD;
                    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 diagnosis. Controlled non-melanoma&#xD;
                    skin cancers, carcinoma in situ of the cervix, resected incidental prostate&#xD;
                    cancer, certain low-grade hematologic malignancies (eg, chronic lymphocytic&#xD;
                    leukemia, follicular lymphoma, etc), or other adequately treated carcinoma in&#xD;
                    situ may be eligible, after discussion 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>
      <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>Hoag Memorial Hospital Presbyterian</name>
        <address>
          <city>Newport Beach</city>
          <state>California</state>
          <zip>92663</zip>
          <country>United States</country>
        </address>
      </facility>
      <investigator>
        <last_name>Michael Demeure, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Rocky Mountain Cancer Centers</name>
        <address>
          <city>Denver</city>
          <state>Colorado</state>
          <zip>80218</zip>
          <country>United States</country>
        </address>
      </facility>
      <investigator>
        <last_name>Allen Cohn, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Texas Oncology</name>
        <address>
          <city>Dallas</city>
          <state>Texas</state>
          <zip>75246</zip>
          <country>United States</country>
        </address>
      </facility>
      <investigator>
        <last_name>Scott Paulson, 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>FYARRO</keyword>
    <keyword>nab-sirolimus</keyword>
    <keyword>ABI-009</keyword>
    <keyword>Neuroendocrine Tumors</keyword>
    <keyword>NET</keyword>
    <keyword>Pancreatic Neuroendocrine Tumor</keyword>
    <keyword>Gastrointestinal Neuroendocrine Tumor</keyword>
    <keyword>Pulmonary Neuroendocrine Tumor</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Neuroendocrine Tumors</mesh_term>
      <mesh_term>Adenoma, Islet Cell</mesh_term>
      <mesh_term>Intestinal Neoplasms</mesh_term>
      <mesh_term>Pancreatic Neoplasms</mesh_term>
      <mesh_term>Stomach Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Sirolimus</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05997056
  org study id: NET-202
  nct id: NCT05997056
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  A Phase 2 multi-center, open-label, single arm study of nab-sirolimus in patients with
        well-differentiated neuroendocrine tumors (NETs) of the gastrointestinal tract, lung, or
        pancreas who have not received prior treatment with mTOR inhibitors
  This is a prospective phase 2 single arm, open-label, multi-institutional study to determine
        the efficacy and safety prospective of nab-sirolimus and patients with functional or
        non-functional, well-differentiated, locally advanced unresectable in metastatic NETs of the
        GI tract, lung, or pancreas.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Efficacy of nab-sirolimus
  time frame: 12 Months
  description: Objective Response Rate (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: Incidence and severity of treatment
  time frame: 12 Months
  description: Incidence and severity of treatment-emergent and treatment-related adverse events (AEs) as assessed by NCI CTCAE v5.0
  measure: Duration of response
  time frame: 12 Months
  description: Determined for patients with BOR of confirmed CR or PR defined as time from scan first showing response by RECIST v1.1 to PD or death
  measure: Disease control rate
  time frame: 12 Months
  description: BOR of confirmed CR or PR (either of any duration) or stable disease (SD) ≥12 weeks by RECISTv1.1 following study treatment initiation
  measure: Time to response
  time frame: 12 Months
  description: Time from first dose of study medication to initial measurement of CR or PR, where CR or PR is subsequently confirmed by RECIST v1.1
  measure: Progression-free survival
  time frame: 12 Months
  description: Number of months from study treatment initiation to the date of disease progression or death due to any cause
  measure: Overall survival
  time frame: 24 Months
  description: Number of months from study treatment initiation to the date of death due to any cause
  arm group label: neuroendocrine tumors
  arm group type: Experimental
  description: Patients with well-differentiated neuroendocrine tumors of the gastrointestinal tract, lung, or pancreas.
  intervention type: Drug
  intervention name: nab-sirolimus
  description: Prospective phase 2 single arm, open-label, multi-institutional study to determine the efficacy and safety prospective of nab-sirolimus administered by IV infusion
  arm group label: neuroendocrine tumors
  other name: ABI-009
  criteria: 
  gender: All
  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: 
  facility: 
  investigator: 
  facility: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Neuroendocrine Tumors
  mesh term: Adenoma, Islet Cell
  mesh term: Intestinal Neoplasms
  mesh term: Pancreatic Neoplasms
  mesh term: Stomach Neoplasms
  mesh term: Sirolimus
  sharing ipd: No