<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/NCT01731925</url>
  </required_header>
  <id_info>
    <org_study_id>SUNLAND D12-01</org_study_id>
    <secondary_id>2012-001098-94</secondary_id>
    <nct_id>NCT01731925</nct_id>
  </id_info>
  <brief_title>A Study of Sunitinib Versus Placebo in Combination With Lanreotide in Patients With Progressive Advanced/Metastatic Midgut Carcinoid Tumors</brief_title>
  <acronym>SUNLAND</acronym>
  <official_title>A RANDOMIZED PHASE II DOUBLE-BLIND TRIAL OF SUNITINIB VERSUS PLACEBO IN COMBINATION WITH LANREOTIDE IN PATIENTS WITH PROGRESSIVE ADVANCED/METASTATIC MIDGUT CARCINOID TUMORS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GERCOR - Multidisciplinary Oncology Cooperative Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ipsen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>GERCOR - Multidisciplinary Oncology Cooperative Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sunitinib may provide an opportunity for a novel therapeutic strategy for the treatment of&#xD;
      subjects with neuroendocrine tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      With the exception of surgery for localized disease, there is presently a lack of available&#xD;
      therapies with proven survival benefit for patients with neuroendocrine tumors (NET).&#xD;
      Available treatment options for unresectable disease include the use of somatostatin analogs,&#xD;
      which may relieve symptoms related to hormonal hypersecretion. The efficacy of cytotoxic&#xD;
      chemotherapy in patients with metastatic carcinoid tumors is also limited. Combinations of&#xD;
      either streptozocin and cyclophosphamide, or streptozocin and 5-fluorouracil, appear to be&#xD;
      inactive, and both regimens are associated with substantial toxicity.&#xD;
&#xD;
      Receptor tyrosine kinases (RTKs) are implicated in deregulated/ autocrine proliferation and&#xD;
      survival of solid and hematologic cancer cells. Sunitinib malate is an orally administered&#xD;
      small molecule that inhibits the tyrosine kinase enzymatic activities of the receptors for&#xD;
      VEGF and PDGF, and also blocks signalling through the KIT, FLT3 and RET pathways.&#xD;
&#xD;
      Therefore, sunitinib malate may provide an opportunity for a novel therapeutic strategy for&#xD;
      the treatment of subjects with NET.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 7, 2013</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>time from date of randomization to first progression of disease (PD) or death for any reason in the absence of documented PD, assessed up to 3 years after the beginning of the study</time_frame>
    <description>To evaluate the efficacy of the combination of sunitinib malate with lanreotide acetate and of placebo with lanreotide acetate regarding progression-free-survival (PFS) as assessed by the investigator, in patients suffering from progressive, advanced/metastatic midgut carcinoid tumors.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>time from date of randomization to date of death, assessed up to 3 years after the beginning of the study</time_frame>
    <description>To evaluate overall survival (OS) in sunitinib- and placebo-treated subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response (OR)</measure>
    <time_frame>from randomization until disease progression, assessed up to 3 years after the beginning of the study</time_frame>
    <description>To evaluate objective response (OR) rate in sunitinib- and placebo-treated subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DR)</measure>
    <time_frame>time from CR or PR to objective tumor progression or to death due to any cause, whichever occurs first, assessed up to 3 years after the beginning of the study</time_frame>
    <description>To evaluate duration of response (DR) in sunitinib- and placebo-treated subjects in subjects achieving a response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to tumor response (TTR)</measure>
    <time_frame>time from date of randomization to first documentation of objective tumor response that is subsequently confirmed.assessed up to 3 years after the beginning of the study</time_frame>
    <description>To assess time to tumor response (TTR) for sunitinib- and placebo-treated subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biological responses</measure>
    <time_frame>from baseline to end of treatment, assessed up to 3 years after the beginning of the study</time_frame>
    <description>To evaluate the best biological responses as assessed using serum chromogranin A and urine 5HIAA for sunitinib- and placebo-treated subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>from visit 1 to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study</time_frame>
    <description>To assess safety and tolerability of sunitinib in the study population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>From screening to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study</time_frame>
    <description>To assess Health related Quality of life (EORTC QLQ C-30).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Carcinoid Tumors</condition>
  <arm_group>
    <arm_group_label>Sunitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sunitinib 37.5 mg daily. Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (for sunitinib). Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lanreotide</intervention_name>
    <description>Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Sunitinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for sunitinib)</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sunitinib</intervention_name>
    <description>Sunitinib 37.5 mg daily</description>
    <arm_group_label>Sunitinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with midgut well-differentiated Grade 1-2 endocrine tumor.&#xD;
&#xD;
          2. Local, locally advanced or metastatic disease documented as progressive by RECIST&#xD;
             v1.1. on CT-scan or MRI at baseline and within 12 months prior to baseline.&#xD;
&#xD;
          3. 5HIAA levels superior to 1.5ULN as measured in each individual centre.&#xD;
&#xD;
          4. Disease that is not amenable to surgery with curative intent.&#xD;
&#xD;
          5. Presence of at least one measurable target lesion for further evaluation according to&#xD;
             RECIST v1.1&#xD;
&#xD;
          6. Adequate organ function&#xD;
&#xD;
          7. ECOG Performance status 0 or 1.&#xD;
&#xD;
          8. Life expectancy superior or equal to 3 months.&#xD;
&#xD;
          9. Age superior or equal to 18 years.&#xD;
&#xD;
         10. Female patients must be surgically sterile or be postmenopausal, or must agree to use&#xD;
             effective contraception during the period of therapy. All female patients with&#xD;
             reproductive potential must have a negative pregnancy test (serum or urine) within 7&#xD;
             days prior to enrollment. Breast feeding is not allowed. Male patients must be&#xD;
             surgically sterile or must agree to use effective contraception during the period of&#xD;
             therapy. The definition of effective contraception will be based on the judgment of&#xD;
             the principal investigator or a designated associate.&#xD;
&#xD;
         11. Able to swallow oral compound.&#xD;
&#xD;
         12. Signed and dated informed consent document indicating that the patient has been&#xD;
             informed of all pertinent aspects of the trial prior to enrollment.&#xD;
&#xD;
         13. Willingness and ability to comply with scheduled visits, treatment plans, laboratory&#xD;
             tests and other study procedures.&#xD;
&#xD;
         14. Registration in a national health care system (CMU included).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with undifferentiated, poorly differentiated gastrointestinal neuroendocrine&#xD;
             tumors, pancreatic neuroendocrine tumors, bronchial carcinoid tumors.&#xD;
&#xD;
          2. Patients with carcinoid tumors with the presence of an obstructive intestinal tumor.&#xD;
&#xD;
          3. Patients with uncontrolled cardiac complication as part of their carcinoid syndrome.&#xD;
&#xD;
          4. Current treatment with any chemotherapy, chemoembolization therapy, immunotherapy, or&#xD;
             investigational anticancer agent&#xD;
&#xD;
          5. Current treatment with dose superior or equal to 120 mg per month of lanreotide&#xD;
&#xD;
          6. Prior treatment with any tyrosine kinase inhibitors or anti-VEGF angiogenic&#xD;
             inhibitors. Prior treatment with non-VEGF-targeted angiogenic inhibitors such as&#xD;
             everolimus or temsirolimus is permitted.&#xD;
&#xD;
          7. Patients who stopped everolimus treatment was less than 4 weeks prior to&#xD;
             randomization.&#xD;
&#xD;
          8. Patients with concomitant treatment with interferon.&#xD;
&#xD;
          9. Patients previously treated with chemotherapy, loco-regional therapy (e.g.,&#xD;
             chemoembolization) or interferon with last administration less than 6 weeks prior to&#xD;
             randomization or with toxicity not resolved to less or equal grade 1 at randomization.&#xD;
&#xD;
         10. Diagnosis of any second malignancy within the last 5 years, except for adequately&#xD;
             treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix&#xD;
             uteri.&#xD;
&#xD;
         11. Treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days,&#xD;
             respectively prior to study drug administration.&#xD;
&#xD;
         12. Concomitant treatment with therapeutic doses of anticoagulants&#xD;
&#xD;
         13. Concomitant treatment with a drug having proarrhythmic potential&#xD;
&#xD;
         14. Unstable systemic diseases including uncontrolled hypertension or active uncontrolled&#xD;
             infections.&#xD;
&#xD;
         15. Current treatment on another clinical trial.&#xD;
&#xD;
         16. Any of the following within the 12 months prior to study drug administration:&#xD;
             myocardial infarction, severe/unstable angina, symptomatic congestive heart failure,&#xD;
             cerebrovascular accident or transient ischemic attack, or pulmonary embolism.&#xD;
&#xD;
         17. Ongoing cardiac dysrhythmias of NCI CTC grade superior or equal to 2, atrial&#xD;
             fibrillation of any grade, or prolongation of the QTc interval to more than 450 msec&#xD;
             for males or more than 470 msec for females.&#xD;
&#xD;
         18. Symptomatic brain metastases, spinal cord compression, or new evidence of brain or&#xD;
             leptomeningeal disease.&#xD;
&#xD;
         19. Left ventricular ejection fraction inferior or equal 50% as measured by either&#xD;
             multigated acquisition scan or echocardiogram.&#xD;
&#xD;
         20. Positive test for human immunodeficiency virus (HIV) or acquired immunodeficiency&#xD;
             syndrome (AIDS) related illness.&#xD;
&#xD;
         21. Patients with complicated, untreated lithiasis of the bile ducts&#xD;
&#xD;
         22. Other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or study&#xD;
             drug administration, or may interfere with the interpretation of study results, and in&#xD;
             the judgment of the investigator would make the patient inappropriate for entry into&#xD;
             this study.&#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>Pascal HAMMEL, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital Beaujon</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint Luc</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Jules Bordet</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ULB Erasme</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Antwerpen</name>
      <address>
        <city>Edegem</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent</name>
      <address>
        <city>Gent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint André</name>
      <address>
        <city>Bordeaux</city>
        <zip>33075</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Beaujon</name>
      <address>
        <city>Clichy</city>
        <zip>92118</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Henri Mondor</name>
      <address>
        <city>Créteil</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Vincent de Paul</name>
      <address>
        <city>Lille</city>
        <zip>59020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69437</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU La Timone</name>
      <address>
        <city>Marseille</city>
        <zip>13005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital St Antoine</name>
      <address>
        <city>Paris</city>
        <zip>75012</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Cochin</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Pitié Salpêtrière</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Mutualiste Montsouris</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Robert Debré</name>
      <address>
        <city>Reims</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Rouen</name>
      <address>
        <city>Rouen</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Trousseau</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>November 19, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2012</study_first_posted>
  <last_update_submitted>January 30, 2017</last_update_submitted>
  <last_update_submitted_qc>January 30, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 31, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>midgut carcinoid tumors</keyword>
  <keyword>progressive</keyword>
  <keyword>advanced</keyword>
  <keyword>metastatic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoid Tumor</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sunitinib</mesh_term>
    <mesh_term>Lanreotide</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01731925
org study id: SUNLAND D12-01
secondary id: 2012-001098-94
nct id: NCT01731925
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Sunitinib may provide an opportunity for a novel therapeutic strategy for the treatment of
      subjects with neuroendocrine tumors.
With the exception of surgery for localized disease, there is presently a lack of available
      therapies with proven survival benefit for patients with neuroendocrine tumors (NET).
      Available treatment options for unresectable disease include the use of somatostatin analogs,
      which may relieve symptoms related to hormonal hypersecretion. The efficacy of cytotoxic
      chemotherapy in patients with metastatic carcinoid tumors is also limited. Combinations of
      either streptozocin and cyclophosphamide, or streptozocin and 5-fluorouracil, appear to be
      inactive, and both regimens are associated with substantial toxicity.

      Receptor tyrosine kinases (RTKs) are implicated in deregulated/ autocrine proliferation and
      survival of solid and hematologic cancer cells. Sunitinib malate is an orally administered
      small molecule that inhibits the tyrosine kinase enzymatic activities of the receptors for
      VEGF and PDGF, and also blocks signalling through the KIT, FLT3 and RET pathways.

      Therefore, sunitinib malate may provide an opportunity for a novel therapeutic strategy for
      the treatment of subjects with NET.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Progression free survival (PFS)
time frame: time from date of randomization to first progression of disease (PD) or death for any reason in the absence of documented PD, assessed up to 3 years after the beginning of the study
description: To evaluate the efficacy of the combination of sunitinib malate with lanreotide acetate and of placebo with lanreotide acetate regarding progression-free-survival (PFS) as assessed by the investigator, in patients suffering from progressive, advanced/metastatic midgut carcinoid tumors.
measure: Overall survival (OS)
time frame: time from date of randomization to date of death, assessed up to 3 years after the beginning of the study
description: To evaluate overall survival (OS) in sunitinib- and placebo-treated subjects.
measure: Objective response (OR)
time frame: from randomization until disease progression, assessed up to 3 years after the beginning of the study
description: To evaluate objective response (OR) rate in sunitinib- and placebo-treated subjects.
measure: Duration of response (DR)
time frame: time from CR or PR to objective tumor progression or to death due to any cause, whichever occurs first, assessed up to 3 years after the beginning of the study
description: To evaluate duration of response (DR) in sunitinib- and placebo-treated subjects in subjects achieving a response.
measure: Time to tumor response (TTR)
time frame: time from date of randomization to first documentation of objective tumor response that is subsequently confirmed.assessed up to 3 years after the beginning of the study
description: To assess time to tumor response (TTR) for sunitinib- and placebo-treated subjects.
measure: Biological responses
time frame: from baseline to end of treatment, assessed up to 3 years after the beginning of the study
description: To evaluate the best biological responses as assessed using serum chromogranin A and urine 5HIAA for sunitinib- and placebo-treated subjects.
measure: Safety
time frame: from visit 1 to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study
description: To assess safety and tolerability of sunitinib in the study population.
measure: Quality of life
time frame: From screening to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study
description: To assess Health related Quality of life (EORTC QLQ C-30).
arm group label: Sunitinib
arm group type: Experimental
description: Sunitinib 37.5 mg daily. Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo (for sunitinib). Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.
intervention type: Drug
intervention name: Lanreotide
description: Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.
arm group label: Placebo
arm group label: Sunitinib
intervention type: Drug
intervention name: Placebo (for sunitinib)
arm group label: Placebo
intervention type: Drug
intervention name: Sunitinib
description: Sunitinib 37.5 mg daily
arm group label: Sunitinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pascal HAMMEL, MD
role: Principal Investigator
affiliation: Hôpital Beaujon
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: France
responsible party type: Sponsor
mesh term: Carcinoid Tumor
mesh term: Sunitinib
mesh term: Lanreotide