<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/NCT03271918</url>
  </required_header>
  <id_info>
    <org_study_id>10675</org_study_id>
    <nct_id>NCT03271918</nct_id>
  </id_info>
  <brief_title>Cabergoline in Nonfunctioning Pituitary Adenomas</brief_title>
  <official_title>Dopamine Agonist Cabergoline in Residual Clinically Nonfunctioning Pituitary Adenoma After Transphenoidal Surgery: A Single Center, Open Label and Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sao Paulo General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Clinically nonfunctioning pituitary adenoma remains the only pituitary tumor subtype for&#xD;
      which no effective medical therapy is available or recommended. We will evaluate the use of&#xD;
      cabergoline in a clinical trial, in order to define the efficacy of this treatment in&#xD;
      nonfunctioning pituitary adenoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nonfunctioning pituitary adenomas (NFPA) are common tumors of sellar region characterized by&#xD;
      the absence of clinically hormonal pituitary secretion. These adenomas are typically not&#xD;
      diagnosed until they become very large and cause compressive neurologic symptons (e.g. visual&#xD;
      impairment or cranial nerve palsy). Most of them are able to synthesized gonadotropins but&#xD;
      not secreted it.&#xD;
&#xD;
      Transsphenoidal surgical resection is the first-choice therapy in NFPA. However, complete&#xD;
      removal is difficult and tumor rest is very common. In these cases, the pragmatic use of&#xD;
      radiotherapy is effective to reduce residual tumor growth or recurrence, but it is related&#xD;
      with severe side effects. Another possibility is the clinical observation, or wait-to-see&#xD;
      approach, but it is associated with tumor progression: 40% in 5-10 years. The efficacy of&#xD;
      some medical treatment are not defined yet.&#xD;
&#xD;
      Since the identification of dopaminergic and somatostatinergic receptors in NFPA, the&#xD;
      pharmacological treatment of the NFPA has been considered as a possibility for treatment. To&#xD;
      date, clinical use of dopamine agonist (DA) in NFPA patients has been evaluated in some&#xD;
      studies. However, these studies present modest and inconclusive results and the DA role in&#xD;
      the NPFA management remains undefined.&#xD;
&#xD;
      In this study, the investigators plan a clinical trial designed to investigate the efficacy&#xD;
      of cabergoline in NFPA individuals with remaining tumor after primary neurosurgery. These&#xD;
      results could help to define the efficacy of DA in NFPA management.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2015</start_date>
  <completion_date type="Actual">August 1, 2017</completion_date>
  <primary_completion_date type="Actual">February 1, 2017</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>A Single Center, Open Label and Randomized Clinical Trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>tumor shrinkage</measure>
    <time_frame>24 months</time_frame>
    <description>shrinkage of tumor rest</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor rest stabilization</measure>
    <time_frame>24 months</time_frame>
    <description>no evidence of tumor growth with experimental therapy</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Cardiovascular Safety</measure>
    <time_frame>24 months</time_frame>
    <description>Absence of Cardiac Valvar Alterations with Cabergoline Use</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">140</enrollment>
  <condition>Pituitary Adenoma</condition>
  <condition>Nonfunctioning Pituitary Adenoma</condition>
  <arm_group>
    <arm_group_label>Study Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group received cabergoline, in a total week dose of 3.5 mg, starting 6 months after transphenoidal surgical approach with evidence of tumoral rest in MRI and pituitary adenoma hystopathological confirmation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>This group was followed, with clinical visits in same frequency of study group, but without intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabergoline</intervention_name>
    <arm_group_label>Study Group</arm_group_label>
    <other_name>dostinex</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  presence of pituitary tumor rest at 6 months after neurosurgery&#xD;
&#xD;
          -  absence of previous hormonal pituitary hypersecretion&#xD;
&#xD;
          -  absence of previous radiotherapy and/or radiosurgery&#xD;
&#xD;
          -  Histopathological exam showing pituitary adenoma&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ACTH immunoexpression at histopathological exam&#xD;
&#xD;
          -  presence of previous radiotherapy and/or radio surgery&#xD;
&#xD;
          -  psychotic psychiatric disease&#xD;
&#xD;
          -  moderate or severe alterations in cardiac valves&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rafael L Batista, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto do Coracao</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Laboratorio de Investigacoes Medicas 25</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>01402003</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <results_reference>
    <citation>Vieira Neto L, Wildemberg LE, Moraes AB, Colli LM, Kasuki L, Marques NV, Gasparetto EL, de Castro M, Takiya CM, Gadelha MR. Dopamine receptor subtype 2 expression profile in nonfunctioning pituitary adenomas and in vivo response to cabergoline therapy. Clin Endocrinol (Oxf). 2015 May;82(5):739-46. doi: 10.1111/cen.12684. Epub 2015 Jan 8.</citation>
    <PMID>25418156</PMID>
  </results_reference>
  <results_reference>
    <citation>Greenman Y, Cooper O, Yaish I, Robenshtok E, Sagiv N, Jonas-Kimchi T, Yuan X, Gertych A, Shimon I, Ram Z, Melmed S, Stern N. Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists. Eur J Endocrinol. 2016 Jul;175(1):63-72. doi: 10.1530/EJE-16-0206. Epub 2016 May 5.</citation>
    <PMID>27150495</PMID>
  </results_reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>September 4, 2017</last_update_submitted>
  <last_update_submitted_qc>September 4, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pituitary Adenoma</keyword>
  <keyword>Dopaminergic Agonist</keyword>
  <keyword>Nonfunctioning Pituitary Adenoma</keyword>
  <keyword>Cabergoline</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenoma</mesh_term>
    <mesh_term>Pituitary Neoplasms</mesh_term>
    <mesh_term>Pituitary Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cabergoline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The protocol and statistical analysis plan will be disposable at researchgate site and by e-mail when it will be asked.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>from Aug, 2017 to indefinite</ipd_time_frame>
    <ipd_access_criteria>free</ipd_access_criteria>
    <ipd_url>https://www.researchgate.net/home</ipd_url>
  </patient_data>
  <!-- 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/NCT03271918
org study id: 10675
nct id: NCT03271918
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Clinically nonfunctioning pituitary adenoma remains the only pituitary tumor subtype for
      which no effective medical therapy is available or recommended. We will evaluate the use of
      cabergoline in a clinical trial, in order to define the efficacy of this treatment in
      nonfunctioning pituitary adenoma.
Nonfunctioning pituitary adenomas (NFPA) are common tumors of sellar region characterized by
      the absence of clinically hormonal pituitary secretion. These adenomas are typically not
      diagnosed until they become very large and cause compressive neurologic symptons (e.g. visual
      impairment or cranial nerve palsy). Most of them are able to synthesized gonadotropins but
      not secreted it.

      Transsphenoidal surgical resection is the first-choice therapy in NFPA. However, complete
      removal is difficult and tumor rest is very common. In these cases, the pragmatic use of
      radiotherapy is effective to reduce residual tumor growth or recurrence, but it is related
      with severe side effects. Another possibility is the clinical observation, or wait-to-see
      approach, but it is associated with tumor progression: 40% in 5-10 years. The efficacy of
      some medical treatment are not defined yet.

      Since the identification of dopaminergic and somatostatinergic receptors in NFPA, the
      pharmacological treatment of the NFPA has been considered as a possibility for treatment. To
      date, clinical use of dopamine agonist (DA) in NFPA patients has been evaluated in some
      studies. However, these studies present modest and inconclusive results and the DA role in
      the NPFA management remains undefined.

      In this study, the investigators plan a clinical trial designed to investigate the efficacy
      of cabergoline in NFPA individuals with remaining tumor after primary neurosurgery. These
      results could help to define the efficacy of DA in NFPA management.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A Single Center, Open Label and Randomized Clinical Trial.
primary purpose: Treatment
masking: None (Open Label)
measure: tumor shrinkage
time frame: 24 months
description: shrinkage of tumor rest
measure: Tumor rest stabilization
time frame: 24 months
description: no evidence of tumor growth with experimental therapy
measure: Cardiovascular Safety
time frame: 24 months
description: Absence of Cardiac Valvar Alterations with Cabergoline Use
arm group label: Study Group
arm group type: Experimental
description: This group received cabergoline, in a total week dose of 3.5 mg, starting 6 months after transphenoidal surgical approach with evidence of tumoral rest in MRI and pituitary adenoma hystopathological confirmation.
arm group label: Control Group
arm group type: No Intervention
description: This group was followed, with clinical visits in same frequency of study group, but without intervention.
intervention type: Drug
intervention name: Cabergoline
arm group label: Study Group
other name: dostinex
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Rafael L Batista, MD
role: Principal Investigator
affiliation: Instituto do Coracao
facility: 
country: Brazil
citation: Vieira Neto L, Wildemberg LE, Moraes AB, Colli LM, Kasuki L, Marques NV, Gasparetto EL, de Castro M, Takiya CM, Gadelha MR. Dopamine receptor subtype 2 expression profile in nonfunctioning pituitary adenomas and in vivo response to cabergoline therapy. Clin Endocrinol (Oxf). 2015 May;82(5):739-46. doi: 10.1111/cen.12684. Epub 2015 Jan 8.
PMID: 25418156
citation: Greenman Y, Cooper O, Yaish I, Robenshtok E, Sagiv N, Jonas-Kimchi T, Yuan X, Gertych A, Shimon I, Ram Z, Melmed S, Stern N. Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists. Eur J Endocrinol. 2016 Jul;175(1):63-72. doi: 10.1530/EJE-16-0206. Epub 2016 May 5.
PMID: 27150495
responsible party type: Sponsor
mesh term: Adenoma
mesh term: Pituitary Neoplasms
mesh term: Pituitary Diseases
mesh term: Cabergoline
sharing ipd: Yes
ipd description: The protocol and statistical analysis plan will be disposable at researchgate site and by e-mail when it will be asked.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: from Aug, 2017 to indefinite
ipd access criteria: free
ipd url: https://www.researchgate.net/home