<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/NCT03781050</url>
  </required_header>
  <id_info>
    <org_study_id>HS-1607</org_study_id>
    <nct_id>NCT03781050</nct_id>
  </id_info>
  <brief_title>Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome</brief_title>
  <official_title>Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Air Force General Hospital of the PLA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking Union Medical College Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective non-randomized open label single arm clinical trial to examine the efficacy and&#xD;
      safety of sirolimus in patients with Peutz-Jeghers Syndrome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PJS (Peutz-Jeghers Syndrome) is mostly caused by mutations in Lkb1 gene, which leads to an&#xD;
      increased activity of mTOR pathway, thus making mTOR inhibitor (sirolimus) a promising&#xD;
      candidate in treatment and prevention of PJS. The efficacy of sirolimus (rapamycin) on PJS&#xD;
      has been demonstrated in mouse model, but no clinical trials have been reported. Our study&#xD;
      was designed as a prospective non-randomized open label single arm clinical trial to examine&#xD;
      its efficacy and safety.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 16, 2018</start_date>
  <completion_date type="Anticipated">July 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>Lesion load (cm2) = A+B. A = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by abdomen and pelvis MRI or small bowel CT reconstruction (in cm2). B = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by digestive endoscope (in cm2). Remarks: 1. If it is impossible to evaluate 3 or more lesions, results of the actual number of lesions should be taken as valid; 2. Lesions evaluated should be correspondent before and after treatment. If the lesion is difficult to assess after treatment, it should be ruled out from the assessment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentration of hemoglobin in blood</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>The value indicates the amount of gastrointestinal bleeding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of albumin in blood</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>The value indicates the status of nutrition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of hsCRP in blood</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>The value indicates the level of inflammation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual analogue score (VAS)</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>The value indicates the level of pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dermatology life quality index (DLQI)</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>The value indicates the status of hyperpigmented macules on the lips and oral mucosa.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>To evaluate safety</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Peutz-Jeghers Syndrome</condition>
  <arm_group>
    <arm_group_label>Rapamycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months&#xD;
For adults: rapamycin, 2 mg a day, orally, for at least 6 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rapamycin</intervention_name>
    <description>For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months&#xD;
For adults: rapamycin, 2 mg a day, orally, for at least 6 months</description>
    <arm_group_label>Rapamycin</arm_group_label>
    <other_name>Sirolimus</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients are diagnosed with PJS.&#xD;
&#xD;
          -  Patients have gastrointestinal polyps related syndromes, including abdominal pain,&#xD;
             abdominal distension, gastrointestinal bleeding, etc, with imageological examination&#xD;
             suggesting intestinal obstruction or intussusception; or whose symptoms recur after&#xD;
             previous digestive endoscopic treatment and surgery; or who are inappropriate or&#xD;
             unwilling to accept the above treatment again and wish to receive pharmacotherapy.&#xD;
&#xD;
          -  Conventional treatment didn't work well in patients combined with PJS-related tumors.&#xD;
&#xD;
          -  Physical condition (ECGO): 0~3&#xD;
&#xD;
          -  Organ function is good and biochemical indices meet the following conditions:&#xD;
&#xD;
               -  AST≤2.5×upper limit of normal value (ULN),&#xD;
&#xD;
               -  ALT≤2.5×upper limit of normal value (ULN),&#xD;
&#xD;
               -  Serum total bilirubin (TSB)≤1.5×upper limit of normal value (ULN),&#xD;
&#xD;
               -  Creatinine≤1.5×upper limit of normal value (ULN).&#xD;
&#xD;
          -  No other medications have been received for intestinal polyps within 3 months prior to&#xD;
             the clinical trial.&#xD;
&#xD;
          -  Patients participate in the trial voluntarily and have signed the informed consent by&#xD;
             the participant or his/her legal guardian.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients underwent a surgery within 2 weeks.&#xD;
&#xD;
          -  Patients may need emergency surgery in the near future.&#xD;
&#xD;
          -  Patients are allergic to any ingredient of rapamycin.&#xD;
&#xD;
          -  Patients suffer from a disease requiring immediate blood transfusion.&#xD;
&#xD;
          -  Patients suffer from any disease or condition that may impact implementation of the&#xD;
             study or interpretation of the results. This type of diseases includes:&#xD;
&#xD;
               -  Known severe blood coagulation disorders&#xD;
&#xD;
               -  Known anemia that is not caused by intestinal polyps&#xD;
&#xD;
               -  Known hemoglobinopathy&#xD;
&#xD;
               -  Other gastrointestinal infectious diseases&#xD;
&#xD;
               -  Serious heart, liver, kidney and other concomitant diseases that may endanger&#xD;
                  lives&#xD;
&#xD;
          -  Patients are in pregnancy and lactation.&#xD;
&#xD;
          -  Alcohol or drug (such as aperient) abuse&#xD;
&#xD;
          -  Patients took part in another clinical trial that may influence this study.&#xD;
&#xD;
          -  The researchers believe that there are other unfavorable reasons for the patient to&#xD;
             become a subject.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jiaolin Zhou, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jiaolin Zhou, MD</last_name>
    <phone>13910136704</phone>
    <email>conniezhjl@yahoo.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences</name>
      <address>
        <city>Beijing</city>
        <state>China/Beijing</state>
        <zip>100000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jiaolin Zhou, MD</last_name>
      <phone>13910136704</phone>
      <email>conniezhjl@yahoo.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Chen HY, Jin XW, Li BR, Zhu M, Li J, Mao GP, Zhang YF, Ning SB. Cancer risk in patients with Peutz-Jeghers syndrome: A retrospective cohort study of 336 cases. Tumour Biol. 2017 Jun;39(6):1010428317705131. doi: 10.1177/1010428317705131.</citation>
    <PMID>28653895</PMID>
  </reference>
  <reference>
    <citation>Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA, Cantley LC. The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell. 2004 Jul;6(1):91-9. doi: 10.1016/j.ccr.2004.06.007.</citation>
    <PMID>15261145</PMID>
  </reference>
  <reference>
    <citation>Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, Muller O, Back W, Zimmer M. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998 Jan;18(1):38-43. doi: 10.1038/ng0198-38.</citation>
    <PMID>9425897</PMID>
  </reference>
  <reference>
    <citation>Wei C, Amos CI, Zhang N, Zhu J, Wang X, Frazier ML. Chemopreventive efficacy of rapamycin on Peutz-Jeghers syndrome in a mouse model. Cancer Lett. 2009 May 18;277(2):149-54. doi: 10.1016/j.canlet.2008.11.036. Epub 2009 Jan 14.</citation>
    <PMID>19147279</PMID>
  </reference>
  <reference>
    <citation>Robinson J, Lai C, Martin A, Nye E, Tomlinson I, Silver A. Oral rapamycin reduces tumour burden and vascularization in Lkb1(+/-) mice. J Pathol. 2009 Sep;219(1):35-40. doi: 10.1002/path.2562.</citation>
    <PMID>19434632</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>January 18, 2019</last_update_submitted>
  <last_update_submitted_qc>January 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Peutz-Jeghers Syndrome (PJS)</keyword>
  <keyword>Rapamycin (sirolimus)</keyword>
  <keyword>Mammalian target of rapamycin (mTOR) inhibitor</keyword>
  <keyword>Treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peutz-Jeghers Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
  </intervention_browse>
  <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>December 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT03781050/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03781050
org study id: HS-1607
nct id: NCT03781050
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
A prospective non-randomized open label single arm clinical trial to examine the efficacy and
      safety of sirolimus in patients with Peutz-Jeghers Syndrome.
PJS (Peutz-Jeghers Syndrome) is mostly caused by mutations in Lkb1 gene, which leads to an
      increased activity of mTOR pathway, thus making mTOR inhibitor (sirolimus) a promising
      candidate in treatment and prevention of PJS. The efficacy of sirolimus (rapamycin) on PJS
      has been demonstrated in mouse model, but no clinical trials have been reported. Our study
      was designed as a prospective non-randomized open label single arm clinical trial to examine
      its efficacy and safety.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps
time frame: The time from start of therapy to 1 year
description: Lesion load (cm2) = A+B. A = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by abdomen and pelvis MRI or small bowel CT reconstruction (in cm2). B = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by digestive endoscope (in cm2). Remarks: 1. If it is impossible to evaluate 3 or more lesions, results of the actual number of lesions should be taken as valid; 2. Lesions evaluated should be correspondent before and after treatment. If the lesion is difficult to assess after treatment, it should be ruled out from the assessment.
measure: Concentration of hemoglobin in blood
time frame: The time from start of therapy to 1 year
description: The value indicates the amount of gastrointestinal bleeding.
measure: Concentration of albumin in blood
time frame: The time from start of therapy to 1 year
description: The value indicates the status of nutrition.
measure: Concentration of hsCRP in blood
time frame: The time from start of therapy to 1 year
description: The value indicates the level of inflammation.
measure: Visual analogue score (VAS)
time frame: The time from start of therapy to 1 year
description: The value indicates the level of pain.
measure: Dermatology life quality index (DLQI)
time frame: The time from start of therapy to 1 year
description: The value indicates the status of hyperpigmented macules on the lips and oral mucosa.
measure: Adverse events
time frame: The time from start of therapy to 1 year
description: To evaluate safety
arm group label: Rapamycin
arm group type: Experimental
description: For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months
For adults: rapamycin, 2 mg a day, orally, for at least 6 months
intervention type: Drug
intervention name: Rapamycin
description: For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months
For adults: rapamycin, 2 mg a day, orally, for at least 6 months
arm group label: Rapamycin
other name: Sirolimus
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Jiaolin Zhou, MD
role: Principal Investigator
affiliation: Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences
last name: Jiaolin Zhou, MD
phone: 13910136704
email: conniezhjl@yahoo.com
facility: 
status: Recruiting
contact: 
country: China
citation: Chen HY, Jin XW, Li BR, Zhu M, Li J, Mao GP, Zhang YF, Ning SB. Cancer risk in patients with Peutz-Jeghers syndrome: A retrospective cohort study of 336 cases. Tumour Biol. 2017 Jun;39(6):1010428317705131. doi: 10.1177/1010428317705131.
PMID: 28653895
citation: Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA, Cantley LC. The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell. 2004 Jul;6(1):91-9. doi: 10.1016/j.ccr.2004.06.007.
PMID: 15261145
citation: Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, Muller O, Back W, Zimmer M. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998 Jan;18(1):38-43. doi: 10.1038/ng0198-38.
PMID: 9425897
citation: Wei C, Amos CI, Zhang N, Zhu J, Wang X, Frazier ML. Chemopreventive efficacy of rapamycin on Peutz-Jeghers syndrome in a mouse model. Cancer Lett. 2009 May 18;277(2):149-54. doi: 10.1016/j.canlet.2008.11.036. Epub 2009 Jan 14.
PMID: 19147279
citation: Robinson J, Lai C, Martin A, Nye E, Tomlinson I, Silver A. Oral rapamycin reduces tumour burden and vascularization in Lkb1(+/-) mice. J Pathol. 2009 Sep;219(1):35-40. doi: 10.1002/path.2562.
PMID: 19434632
responsible party type: Sponsor
mesh term: Peutz-Jeghers Syndrome
mesh term: Syndrome
mesh term: Sirolimus
provided document: 