<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/NCT03280979</url>
  </required_header>
  <id_info>
    <org_study_id>RR&amp;HDMPGTN</org_study_id>
    <nct_id>NCT03280979</nct_id>
  </id_info>
  <brief_title>Rescue Regimen and High Dose Methotrexate in Management of Presistent Gestational Trophoplastic Neoplasia</brief_title>
  <official_title>Comparison Between Rescue Regimen and High Dose Methotrexate in the Managment of Presistent Gestational Trophoplastic Neoplasia :( A Randomized Controlled Trial )</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gestational trophoblastic neoplasia (GTN) are malignant lesions that arise from abnormal&#xD;
      proliferation of placental trophoblast. The pathologic conditions that make up this entity&#xD;
      include invasive partial and complete hydatidiform mole, choriocarcinoma, placental site&#xD;
      trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). GTN often arises after&#xD;
      molar pregnancies but can also occur after any gestation including miscarriages and term&#xD;
      pregnancies. In the United States, hydatidiform moles are observed in approximately 1/600&#xD;
      therapeutic abortions and 1/1000-2000 pregnancies . Most cases of GTN are diagnosed when the&#xD;
      serum hCG levels plateau or rise in patients being observed after the diagnosis of&#xD;
      hydatidiform mole.These malignancies are highly susceptible to chemotherapy and it is often&#xD;
      possible to achieve cure while preserving the woman's reproductive function&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      When reporting GTN data, it is useful to use both the FIGO anatomic staging system and&#xD;
      prognostic scoring system . A FIGO score of 6 or less indicates low-risk GTN whereas a score&#xD;
      of 7 or more identifies high-risk disease.&#xD;
&#xD;
      Table 1- FIGO Anatomical staging of gestational trophoblastic neoplasia:&#xD;
&#xD;
      Stage I Disease confined to the uterus Stage II Disease extends to the outside of the uterus,&#xD;
      but is limited to the genital structures Stage III Disease extends to the lungs, with or&#xD;
      without genital tract involvement Stage IV All other metastatic sites&#xD;
&#xD;
      Table 2- FIGO Scoring system:&#xD;
&#xD;
      FIGO SCORING 0 1 2 4 Age (years) Antecedent pregnancy Interval months from end of index&#xD;
      pregnancy to treatment Pretreatment serum hCG (iu/l) Largest tumour size, including uterus&#xD;
      Site of metastases Number of metastases Previous failed chemotherapy &lt;40 ≥40 - - mole&#xD;
      abortion term &lt;4 4-6 7-12 &gt;12 &lt;1000 1000-10000 10000-100000 &gt;100000 &lt;3cm 3-4cm ≥5 - Lung&#xD;
      spleen&amp;kidney GIT liver&amp;brain&#xD;
&#xD;
        -  1-4 5-8 &gt;8&#xD;
&#xD;
        -  - 1 drug 2 or more drugs&#xD;
&#xD;
      RCOG guidelines (No. 38February 2010 ) recommends the use of rescue regimen of alternating&#xD;
      methotrexate( MTX) and leucoverin for 8 days (class D). However, several protocols using MTX&#xD;
      were described. No prospective randomised controlled trials have been done to compare the&#xD;
      efficacy of resue regimen with the ther protocols. In a retrospective study done showed that&#xD;
      high dose methotrexate regimen is more effective than the rescue regimen.&#xD;
&#xD;
      In addition, several concerns have been raised towards the use of leucoverin with&#xD;
      methotrexate, although reducing the side effects, however, it may increase the resistence to&#xD;
      the effect of MTX .&#xD;
&#xD;
      On the other hand, High dose regimen offers a less hospital stay which may be more convenient&#xD;
      to the patients, together with the same incidence of side effects.&#xD;
&#xD;
      In our study we are going to compare the efficacy and tolerance of both regimens in patients&#xD;
      diagnosed to have low risk PGTN.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">October 2017</start_date>
  <completion_date type="Anticipated">October 2019</completion_date>
  <primary_completion_date type="Anticipated">July 2019</primary_completion_date>
  <phase>Phase 2/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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>cure rate</measure>
    <time_frame>12 month</time_frame>
    <description>cure rate till B hcG is negative and then 2 consolidation regimens</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>decline in Bhcg</measure>
    <time_frame>12 month</time_frame>
    <description>Number of cycles for decline in BhCG</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">170</enrollment>
  <condition>Gestational Trophoblastic Disease</condition>
  <arm_group>
    <arm_group_label>study group1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the rescue regimen , we administer MTX in an eight-day treatment regimen consisting of four administrations of MTX given at 1 mg/kg I.M. every other day with folinic acid 0.1 mg/kg I.M,. given on intervening days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>study group2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the high dose MTX protocol, the patients will receive 100 mg/m2 intravenous (IV) MTX bolus followed by 200 mg/m2IV MTX infused over 12 hours followed by folinic acid</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rescue regimen</intervention_name>
    <description>In the rescue regimen , we administer MTX in an eight-day treatment regimen consisting of four administrations of TX given at 1 mg/kg I.M. every other day with folinic acid 0.1 mg/kg I.M,. given on intervening days.</description>
    <arm_group_label>study group1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>high dose methotrxate</intervention_name>
    <description>In the high dose MTX protocol, the patients will receive 100 mg/m2 intravenous (IV) MTX bolus followed by 200 mg/m2IV MTX infused over 12 hours followed by folinic acid</description>
    <arm_group_label>study group2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: 18-50&#xD;
&#xD;
          -  BW: 50-100 kg&#xD;
&#xD;
          -  willing and consenting to be enrolled in the study&#xD;
&#xD;
          -  Absence of active vaginal bleeding which requires surgical intervention • - WHO score&#xD;
             &lt;6&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Renal and liver dysfunction or blood dyscariasis&#xD;
&#xD;
          -  high risk persistent gestational trophoblastic disease.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>zahraa magdy, md</last_name>
    <phone>01002603379</phone>
    <email>zahraamagdy92@yahoo.com</email>
  </overall_contact>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>September 11, 2017</last_update_submitted>
  <last_update_submitted_qc>September 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Zahraa Magdy</investigator_full_name>
    <investigator_title>principal investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gestational Trophoblastic Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
  </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/NCT03280979
org study id: RR&HDMPGTN
nct id: NCT03280979
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Gestational trophoblastic neoplasia (GTN) are malignant lesions that arise from abnormal
      proliferation of placental trophoblast. The pathologic conditions that make up this entity
      include invasive partial and complete hydatidiform mole, choriocarcinoma, placental site
      trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). GTN often arises after
      molar pregnancies but can also occur after any gestation including miscarriages and term
      pregnancies. In the United States, hydatidiform moles are observed in approximately 1/600
      therapeutic abortions and 1/1000-2000 pregnancies . Most cases of GTN are diagnosed when the
      serum hCG levels plateau or rise in patients being observed after the diagnosis of
      hydatidiform mole.These malignancies are highly susceptible to chemotherapy and it is often
      possible to achieve cure while preserving the woman's reproductive function
When reporting GTN data, it is useful to use both the FIGO anatomic staging system and
      prognostic scoring system . A FIGO score of 6 or less indicates low-risk GTN whereas a score
      of 7 or more identifies high-risk disease.

      Table 1- FIGO Anatomical staging of gestational trophoblastic neoplasia:

      Stage I Disease confined to the uterus Stage II Disease extends to the outside of the uterus,
      but is limited to the genital structures Stage III Disease extends to the lungs, with or
      without genital tract involvement Stage IV All other metastatic sites

      Table 2- FIGO Scoring system:

      FIGO SCORING 0 1 2 4 Age (years) Antecedent pregnancy Interval months from end of index
      pregnancy to treatment Pretreatment serum hCG (iu/l) Largest tumour size, including uterus
      Site of metastases Number of metastases Previous failed chemotherapy <40 ≥40 - - mole
      abortion term <4 4-6 7-12 >12 <1000 1000-10000 10000-100000 >100000 <3cm 3-4cm ≥5 - Lung
      spleen&kidney GIT liver&brain

        -  1-4 5-8 >8

        -  - 1 drug 2 or more drugs

      RCOG guidelines (No. 38February 2010 ) recommends the use of rescue regimen of alternating
      methotrexate( MTX) and leucoverin for 8 days (class D). However, several protocols using MTX
      were described. No prospective randomised controlled trials have been done to compare the
      efficacy of resue regimen with the ther protocols. In a retrospective study done showed that
      high dose methotrexate regimen is more effective than the rescue regimen.

      In addition, several concerns have been raised towards the use of leucoverin with
      methotrexate, although reducing the side effects, however, it may increase the resistence to
      the effect of MTX .

      On the other hand, High dose regimen offers a less hospital stay which may be more convenient
      to the patients, together with the same incidence of side effects.

      In our study we are going to compare the efficacy and tolerance of both regimens in patients
      diagnosed to have low risk PGTN.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: cure rate
time frame: 12 month
description: cure rate till B hcG is negative and then 2 consolidation regimens
measure: decline in Bhcg
time frame: 12 month
description: Number of cycles for decline in BhCG
arm group label: study group1
arm group type: Experimental
description: In the rescue regimen , we administer MTX in an eight-day treatment regimen consisting of four administrations of MTX given at 1 mg/kg I.M. every other day with folinic acid 0.1 mg/kg I.M,. given on intervening days.
arm group label: study group2
arm group type: Experimental
description: In the high dose MTX protocol, the patients will receive 100 mg/m2 intravenous (IV) MTX bolus followed by 200 mg/m2IV MTX infused over 12 hours followed by folinic acid
intervention type: Drug
intervention name: rescue regimen
description: In the rescue regimen , we administer MTX in an eight-day treatment regimen consisting of four administrations of TX given at 1 mg/kg I.M. every other day with folinic acid 0.1 mg/kg I.M,. given on intervening days.
arm group label: study group1
intervention type: Drug
intervention name: high dose methotrxate
description: In the high dose MTX protocol, the patients will receive 100 mg/m2 intravenous (IV) MTX bolus followed by 200 mg/m2IV MTX infused over 12 hours followed by folinic acid
arm group label: study group2
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: zahraa magdy, md
phone: 01002603379
email: zahraamagdy92@yahoo.com
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Zahraa Magdy
investigator title: principal investigator
mesh term: Gestational Trophoblastic Disease
sharing ipd: Yes
ipd info type: Study Protocol