<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/NCT03043664</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00074917</org_study_id>
    <nct_id>NCT03043664</nct_id>
  </id_info>
  <brief_title>Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors</brief_title>
  <acronym>PLANET</acronym>
  <official_title>Phase Ib/II Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ipsen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</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>
      This study is for patients with non-resectable, recurrent, or metastatic well or moderately&#xD;
      differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs).&#xD;
&#xD;
      The study will be conducted in two stages: 1) Safety Run-In and 2) Expanded Cohort.&#xD;
&#xD;
        1. Safety run-in: The first stage will include a safety run-in of 6 patients treated with&#xD;
           pembrolizumab 200 mg intravenous (IV) every 3 weeks and lanreotide depot 90mg&#xD;
           subcutaneous (SQ) every 3 weeks. Up to 6 patients at the Duke Cancer Institute will be&#xD;
           accrued at the starting dose level. If one or less subject meets treatment-related&#xD;
           discontinuation criteria (as specified in the protocol) during Cycle 1, then the study&#xD;
           will proceed to the second stage, Expanded Cohort.&#xD;
&#xD;
        2. Expanded Cohort: Patients will be treated with pembrolizumab 200mg IV every 3 weeks and&#xD;
           lanreotide depot 90mg SQ every 3 weeks as determined by the Safety Run-In Cohort.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">June 7, 2022</completion_date>
  <primary_completion_date type="Actual">May 3, 2021</primary_completion_date>
  <phase>Phase 1/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>
    <intervention_model_description>Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)</measure>
    <time_frame>Approximately every 12 weeks until study completion (up to 2 years)</time_frame>
    <description>ORR is calculated as the number of people with a complete response (CR) or partial response (PR), divided by the total number of people treated. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. A lower limit of the true ORR will be estimated by the 90% exact lower confidence bound (LCB) for the binomial proportion. A 90% LCB of &lt; 0.1 will be considered not to be of clinical value. If the 90% LCB is ≥ 0.1, the regimen will be considered efficacious.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Experiencing Treatment-related AEs Leading to Drug Discontinuations During the First 12 Weeks of Treatment</measure>
    <time_frame>First 12 weeks of treatment</time_frame>
    <description>Adverse events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Months of Progression-free Survival (PFS)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Months from treatment start date until the date of first documented radiographic progression or date of death from any cause (whichever is first); assessed up to 48 weeks after the last subject has finished study drug regimen. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Months of Overall Survival (OS)</measure>
    <time_frame>Up to 59 months</time_frame>
    <description>Months from treatment start date until the date of death from any cause; assessed up to 48 weeks after the last subject has finished the study drug regimen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR as Measured by Immune-related Response Criteria (irRC)</measure>
    <time_frame>Approximately every 12 weeks until study completion (up to 2 years)</time_frame>
    <description>Treatment response as assessed by irRC instead of RECIST v1.1. ORR is calculated as the number of people with a complete response (CR) or partial response (PR), divided by the total number of people treated. Complete response is defined as complete disappearance of all lesions (whether measurable or not, and no new lesions), confirmed by a repeat, consecutive assessment no less than 4 weeks from the date first documented. Partial response is defined as a decrease in tumor burden ≥ 50% relative to baseline, confirmed by a consecutive assessment at least 4 weeks after first documentation. A lower limit of the true ORR will be estimated by the 90% exact lower confidence bound (LCB) for the binomial proportion.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Gastroenteropancreatic Neuroendocrine Tumors</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lanreotide</intervention_name>
    <description>Somatuline depot (lanreotide) 90 mg SQ every 3 weeks</description>
    <arm_group_label>Arm 1</arm_group_label>
    <other_name>Somatuline Depot</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Keytruda (pembrolizumab) 200 mg IV every 3 weeks</description>
    <arm_group_label>Arm 1</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to provide written informed consent for the trial.&#xD;
&#xD;
          2. At least 18 years of age on day of signing informed consent.&#xD;
&#xD;
          3. Non-resectable, recurrent, or metastatic well- or moderately-differentiated&#xD;
             gastroenteropancreatic neuroendocrine tumor (GEP-NETs) with disease progression within&#xD;
             the last 12 months. (Patients who have received prior local therapy, including but not&#xD;
             limited to embolization, chemoembolization, radiofrequency ablation, radiation&#xD;
             therapy, are eligible provided that measurable disease falls outside the treatment&#xD;
             field or within the field but has shown an increase of &gt; 20% in the size. Prior local&#xD;
             therapy must be completed at least 4 weeks prior to the baseline scan.)&#xD;
&#xD;
          4. Prior somatostatin analogue therapy. (Patients should receive the first dose of study&#xD;
             drug no sooner than 4 weeks from the last dose of somatostatin analogue.)&#xD;
&#xD;
          5. At least one measurable lesion based on RECIST version 1.1.&#xD;
&#xD;
          6. Agrees to provide available archived tumor tissue specimen. (Patients who do not have&#xD;
             available archived tumor must agree to have core or excisional biopsy of a tumor&#xD;
             lesion obtained up to 42 days prior to the first dose of study drug, if safely&#xD;
             accessible. If archived tissue is not available and the tumor is not amenable to safe&#xD;
             biopsy, subject is still eligible to participate.)&#xD;
&#xD;
          7. ECOG performance status of 0 or 1.&#xD;
&#xD;
          8. Adequate organ function defined as:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,500 /mcL&#xD;
&#xD;
               -  Platelets ≥ 100,000 /mcL&#xD;
&#xD;
               -  Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or EPO dependency (within&#xD;
                  7 days of assessment)&#xD;
&#xD;
               -  Serum creatinine OR calculated creatinine clearance (CrCL) per institutional&#xD;
                  standard (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 X upper&#xD;
                  limit of normal (ULN) OR ≥ 60 mL/min for subject with creatinine levels &gt; 1.5 X&#xD;
                  institutional ULN&#xD;
&#xD;
               -  Serum total bilirubin ≤ 1.5 X ULN&#xD;
&#xD;
               -  AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver&#xD;
                  metastases&#xD;
&#xD;
               -  Albumin ≥ 2.5 mg/dL&#xD;
&#xD;
          9. Negative serum pregnancy test within ≤ 7 days prior to the first dose of study drug,&#xD;
             for women of childbearing potential only.&#xD;
&#xD;
         10. Female subjects agree to use two birth control methods, be surgically sterile, or&#xD;
             abstain from heterosexual activity for the course of the study through 120 days after&#xD;
             the last dose of study drug.&#xD;
&#xD;
         11. Male subjects agree to use an adequate method of contraception for the course of the&#xD;
             study through 120 days after the last dose of study drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Tumor mitotic rate &gt;20/10 hpf and/or Ki67 index &gt;20% (if available).&#xD;
&#xD;
          2. Currently participating and receiving study therapy or has participated in a study of&#xD;
             an investigational agent and received study therapy or used an investigational device&#xD;
             within 4 weeks of the first dose of study drug.&#xD;
&#xD;
          3. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other&#xD;
             form of immunosuppressive therapy within 7 days prior to the first dose of study drug.&#xD;
&#xD;
          4. Known history of active TB (Bacillus Tuberculosis).&#xD;
&#xD;
          5. Hypersensitivity to pembrolizumab or lanreotide or any of their excipients.&#xD;
&#xD;
          6. Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of&#xD;
             study drug or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse&#xD;
             events due to a previously administered agent.&#xD;
&#xD;
          7. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2&#xD;
             weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1&#xD;
             or at baseline) from adverse events due to a previously administered agent. Patients&#xD;
             with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the&#xD;
             study.&#xD;
&#xD;
          8. Prior major surgery within 2 weeks prior to the first dose of study drug or who has&#xD;
             not recovered adequately from the toxicity and/or complications from the intervention.&#xD;
&#xD;
          9. Known additional malignancy that is progressing or requires active treatment.&#xD;
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the&#xD;
             skin that has undergone potentially curative therapy or in situ cervical cancer.&#xD;
&#xD;
         10. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.&#xD;
             Subjects with previously treated brain metastases may participate provided they are&#xD;
             stable (without evidence of progression by imaging for at least four weeks prior to&#xD;
             the first dose of trial treatment and any neurologic symptoms have returned to&#xD;
             baseline), have no evidence of new or enlarging brain metastases, and are not using&#xD;
             steroids for at least 7 days prior to the first dose of study drug. This exception&#xD;
             does not include carcinomatous meningitis which is excluded regardless of clinical&#xD;
             stability.&#xD;
&#xD;
         11. Active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment.&#xD;
&#xD;
         12. Known history of, or any evidence of active, non-infectious pneumonitis.&#xD;
&#xD;
         13. Active infection requiring systemic therapy.&#xD;
&#xD;
         14. History or current evidence of any condition, therapy, or laboratory abnormality that&#xD;
             might confound the results of the trial, interfere with the subject's participation&#xD;
             for the full duration of the trial, or is not in the best interest of the subject to&#xD;
             participate, in the opinion of the treating physician.&#xD;
&#xD;
         15. Known psychiatric or substance abuse disorders that would interfere with cooperation&#xD;
             with the requirements of the trial.&#xD;
&#xD;
         16. Pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of study drug.&#xD;
&#xD;
         17. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.&#xD;
&#xD;
         18. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
         19. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA&#xD;
             [qualitative] is detected).&#xD;
&#xD;
         20. Live vaccine within 30 days of planned start of study drug regimen. Seasonal influenza&#xD;
             vaccines for injection are generally inactivated flu vaccines and are allowed; however&#xD;
             intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are&#xD;
             not allowed.&#xD;
&#xD;
         21. History of intolerance to somatostatin analogues.&#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>Michael Morse, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lexington Medical Center</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>February 1, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 6, 2017</study_first_posted>
  <results_first_submitted>May 3, 2022</results_first_submitted>
  <results_first_submitted_qc>September 1, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 28, 2022</results_first_posted>
  <last_update_submitted>June 12, 2023</last_update_submitted>
  <last_update_submitted_qc>June 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>GEP-NET</keyword>
  <keyword>pembrolizumab</keyword>
  <keyword>lanreotide</keyword>
  <keyword>PD-1</keyword>
  <keyword>Keytruda</keyword>
  <keyword>Somatuline Depot</keyword>
  <keyword>PD-L1</keyword>
  <keyword>anti-PD-1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuroendocrine Tumors</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>Pembrolizumab</mesh_term>
    <mesh_term>Lanreotide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 7, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT03043664/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 23, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT03043664/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were recruited at Duke University Medical Center from 5/15/2017 to 2/13/2020.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Somatuline Depot and Keytruda</title>
          <description>Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Somatuline Depot and Keytruda</title>
          <description>Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="22"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.2" spread="8.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)</title>
        <description>ORR is calculated as the number of people with a complete response (CR) or partial response (PR), divided by the total number of people treated. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. A lower limit of the true ORR will be estimated by the 90% exact lower confidence bound (LCB) for the binomial proportion. A 90% LCB of &lt; 0.1 will be considered not to be of clinical value. If the 90% LCB is ≥ 0.1, the regimen will be considered efficacious.</description>
        <time_frame>Approximately every 12 weeks until study completion (up to 2 years)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Somatuline Depot and Keytruda</title>
            <description>Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)</title>
          <description>ORR is calculated as the number of people with a complete response (CR) or partial response (PR), divided by the total number of people treated. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. A lower limit of the true ORR will be estimated by the 90% exact lower confidence bound (LCB) for the binomial proportion. A 90% LCB of &lt; 0.1 will be considered not to be of clinical value. If the 90% LCB is ≥ 0.1, the regimen will be considered efficacious.</description>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.045" lower_limit="0" upper_limit="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Experiencing Treatment-related AEs Leading to Drug Discontinuations During the First 12 Weeks of Treatment</title>
        <description>Adverse events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.</description>
        <time_frame>First 12 weeks of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Somatuline Depot and Keytruda</title>
            <description>Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Experiencing Treatment-related AEs Leading to Drug Discontinuations During the First 12 Weeks of Treatment</title>
          <description>Adverse events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Months of Progression-free Survival (PFS)</title>
        <description>Months from treatment start date until the date of first documented radiographic progression or date of death from any cause (whichever is first); assessed up to 48 weeks after the last subject has finished study drug regimen. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.</description>
        <time_frame>Up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Somatuline Depot and Keytruda</title>
            <description>Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Months of Progression-free Survival (PFS)</title>
          <description>Months from treatment start date until the date of first documented radiographic progression or date of death from any cause (whichever is first); assessed up to 48 weeks after the last subject has finished study drug regimen. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.04" lower_limit="2.7" upper_limit="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Months of Overall Survival (OS)</title>
        <description>Months from treatment start date until the date of death from any cause; assessed up to 48 weeks after the last subject has finished the study drug regimen</description>
        <time_frame>Up to 59 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Somatuline Depot and Keytruda</title>
            <description>Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Months of Overall Survival (OS)</title>
          <description>Months from treatment start date until the date of death from any cause; assessed up to 48 weeks after the last subject has finished the study drug regimen</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.6" lower_limit="21.0" upper_limit="NA">There is not a sufficient number of events after the median time point to estimate the upper confidence limit. Most patients past the median are censored.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR as Measured by Immune-related Response Criteria (irRC)</title>
        <description>Treatment response as assessed by irRC instead of RECIST v1.1. ORR is calculated as the number of people with a complete response (CR) or partial response (PR), divided by the total number of people treated. Complete response is defined as complete disappearance of all lesions (whether measurable or not, and no new lesions), confirmed by a repeat, consecutive assessment no less than 4 weeks from the date first documented. Partial response is defined as a decrease in tumor burden ≥ 50% relative to baseline, confirmed by a consecutive assessment at least 4 weeks after first documentation. A lower limit of the true ORR will be estimated by the 90% exact lower confidence bound (LCB) for the binomial proportion.</description>
        <time_frame>Approximately every 12 weeks until study completion (up to 2 years)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Somatuline Depot and Keytruda</title>
            <description>Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>ORR as Measured by Immune-related Response Criteria (irRC)</title>
          <description>Treatment response as assessed by irRC instead of RECIST v1.1. ORR is calculated as the number of people with a complete response (CR) or partial response (PR), divided by the total number of people treated. Complete response is defined as complete disappearance of all lesions (whether measurable or not, and no new lesions), confirmed by a repeat, consecutive assessment no less than 4 weeks from the date first documented. Partial response is defined as a decrease in tumor burden ≥ 50% relative to baseline, confirmed by a consecutive assessment at least 4 weeks after first documentation. A lower limit of the true ORR will be estimated by the 90% exact lower confidence bound (LCB) for the binomial proportion.</description>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.045" lower_limit="0" upper_limit="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 25 months for adverse events; up to 59 months for all-cause mortality</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Somatuline Depot and Keytruda</title>
          <description>Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, Specify, Salmonella</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, Specify, Non Fasting Hyperglycemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Sleep apnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Specify, Injection Site Reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Michael Morse, MD</name_or_title>
      <organization>Duke University Medical Center</organization>
      <phone>919-668-1861</phone>
      <email>michael.morse@duke.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03043664
org study id: Pro00074917
nct id: NCT03043664
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study is for patients with non-resectable, recurrent, or metastatic well or moderately
      differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

      The study will be conducted in two stages: 1) Safety Run-In and 2) Expanded Cohort.

        1. Safety run-in: The first stage will include a safety run-in of 6 patients treated with
           pembrolizumab 200 mg intravenous (IV) every 3 weeks and lanreotide depot 90mg
           subcutaneous (SQ) every 3 weeks. Up to 6 patients at the Duke Cancer Institute will be
           accrued at the starting dose level. If one or less subject meets treatment-related
           discontinuation criteria (as specified in the protocol) during Cycle 1, then the study
           will proceed to the second stage, Expanded Cohort.

        2. Expanded Cohort: Patients will be treated with pembrolizumab 200mg IV every 3 weeks and
           lanreotide depot 90mg SQ every 3 weeks as determined by the Safety Run-In Cohort.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
time frame: Approximately every 12 weeks until study completion (up to 2 years)
description: ORR is calculated as the number of people with a complete response (CR) or partial response (PR), divided by the total number of people treated. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. A lower limit of the true ORR will be estimated by the 90% exact lower confidence bound (LCB) for the binomial proportion. A 90% LCB of < 0.1 will be considered not to be of clinical value. If the 90% LCB is ≥ 0.1, the regimen will be considered efficacious.
measure: Number of Participants Experiencing Treatment-related AEs Leading to Drug Discontinuations During the First 12 Weeks of Treatment
time frame: First 12 weeks of treatment
description: Adverse events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
measure: Months of Progression-free Survival (PFS)
time frame: Up to 3 years
description: Months from treatment start date until the date of first documented radiographic progression or date of death from any cause (whichever is first); assessed up to 48 weeks after the last subject has finished study drug regimen. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
measure: Months of Overall Survival (OS)
time frame: Up to 59 months
description: Months from treatment start date until the date of death from any cause; assessed up to 48 weeks after the last subject has finished the study drug regimen
measure: ORR as Measured by Immune-related Response Criteria (irRC)
time frame: Approximately every 12 weeks until study completion (up to 2 years)
description: Treatment response as assessed by irRC instead of RECIST v1.1. ORR is calculated as the number of people with a complete response (CR) or partial response (PR), divided by the total number of people treated. Complete response is defined as complete disappearance of all lesions (whether measurable or not, and no new lesions), confirmed by a repeat, consecutive assessment no less than 4 weeks from the date first documented. Partial response is defined as a decrease in tumor burden ≥ 50% relative to baseline, confirmed by a consecutive assessment at least 4 weeks after first documentation. A lower limit of the true ORR will be estimated by the 90% exact lower confidence bound (LCB) for the binomial proportion.
arm group label: Arm 1
arm group type: Experimental
description: Keytruda (pembrolizumab) 200 mg intravenous (IV) infusion every 3 weeks and Somatuline Depot (lanreotide) 90 mg subcutaneous (SQ) injection every 3 weeks.
intervention type: Drug
intervention name: Lanreotide
description: Somatuline depot (lanreotide) 90 mg SQ every 3 weeks
arm group label: Arm 1
other name: Somatuline Depot
intervention type: Drug
intervention name: Pembrolizumab
description: Keytruda (pembrolizumab) 200 mg IV every 3 weeks
arm group label: Arm 1
other name: Keytruda
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Morse, MD
role: Principal Investigator
affiliation: Duke University
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neuroendocrine Tumors
mesh term: Intestinal Neoplasms
mesh term: Pancreatic Neoplasms
mesh term: Stomach Neoplasms
mesh term: Pembrolizumab
mesh term: Lanreotide
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 