<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/NCT01669369</url>
  </required_header>
  <id_info>
    <org_study_id>Lithium-5010</org_study_id>
    <nct_id>NCT01669369</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Lithium Carbonate Combined With Neo-adjuvant Chemotherapy to Treat Osteosarcoma</brief_title>
  <acronym>Li2CO3</acronym>
  <official_title>A Prospected Randomized Multicenter Clinical Trial of Lithium Carbonate Combined With Neo-adjuvant Chemotherapy to Treat Osteosarcoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Qilu Hospital of Shandong University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nanfang Hospital, Southern Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shenzhen Second People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangdong Provincial Hospital of Traditional Chinese Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shanghai 6th People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether Lithium Carbonate combined with&#xD;
      neo-adjuvant chemotherapy improve the prognosis of osteosarcoma&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence,&#xD;
      the prognosis for the disease is poor. What's more, chemotherapy resistance and serious&#xD;
      myelosuppression occur frequently in clinical further hindered canonical adjuvant&#xD;
      chemotherapy. In our previous researches, we observed that GSK-3B positively regulates the&#xD;
      NF-kB pathway to promote proliferation and tumorigenicity in osteosarcoma cell. Targeted&#xD;
      inhibition of GSK3beta showed an obvious antitumor effect. It is a promising therapeutic&#xD;
      target in osteosarcoma, especially if GSK-3b inhibition is combined with chemotherapeutic&#xD;
      drugs. Lithium carbonate, commonly use in clinical application because of its fine quality&#xD;
      and cheap price, was proven to be effected as a kind of GSK3beta inhibitor and stimulating&#xD;
      factor of peripheral blood leukocyte. Therefore, lithium carbonate theoretically possesses&#xD;
      effects of both anti-tumor as well as improvement of myelosuppression. We look forward to the&#xD;
      results of clinical trials to test the effect of combinations of chemical drugs with lithium&#xD;
      carbonate on myelosuppression, disease-free survival rate and lung metastasis rate in&#xD;
      patients with osteosarcoma who treated with conventional chemotherapeutic regimens and wide&#xD;
      resection. This study is a multi-centre, double-blind, randomized clinical trial phase 4. The&#xD;
      inclusion criterion is patients with primary osteosarcoma in femur, tibia and humerus（IIB）.&#xD;
      With the help of statistic method, 400 patients were randomly divided into two groups&#xD;
      according to sequence of entering the group: lithium carbonate group and control group (1:1).&#xD;
      Patients were suggesting continuing this trial until the end of the chemotherapy regimen or&#xD;
      being confirmed as disease progression by RECIST guiding principles. According to their&#xD;
      histological types, patients are analyzed using subgroup analysis. Disease evaluation will be&#xD;
      conducted every 8 weeks. A follow-up to count the overall survival rate after grouping was&#xD;
      performed within at least 24 months or at most 120 months. Our study may represent a novel&#xD;
      and feasible approach by combination of conventional chemotherapy drugs and targeted drugs.&#xD;
      More importantly, it may hopefully be a promising strategy to improve overall survival of&#xD;
      osteosarcoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 4</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>progression-free survival,incidence of chemotherapy-induced myelosuppression</measure>
    <time_frame>at least 24 months or at most 120 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>over-all survival,metastasis-free survival</measure>
    <time_frame>at least 24 months or at most 120 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">400</enrollment>
  <condition>Osteosarcoma</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The shape,color and smell of placebo are similar to Lithium Carbonate tablet used in the treatment arm.Patients in this arm take placebo twice a day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lithium Carbonate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in this arm take Lithium Carbonate twice a day with a dose of 20-25mg/kg/d.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lithium Carbonate</intervention_name>
    <description>400 patients were randomly divided into two groups according to sequence of entering the group: lithium carbonate group and control group (1:1). Patients in lithium carbonate group were treated with combinations of chemotherapy and lithium carbonate, the control group were treated with chemotherapy only. Patients were suggesting continuing this trial until the end of the chemotherapy regimen or being confirmed as disease progression by RECIST.</description>
    <arm_group_label>Lithium Carbonate</arm_group_label>
    <other_name>Lithobid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The shape,color and smell of placebo are similar to Lithium Carbonate tablet used in the treatment arm.Patients in this arm take placebo twice a day.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>PLACEBO TREATMENT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  histologically diagnosed primary classical osteosarcoma in extremities&#xD;
&#xD;
          -  staging IIB&#xD;
&#xD;
          -  MRI showing no skip lesion&#xD;
&#xD;
          -  receive standard neo-adjuvant chemotherapy, adjuvant chemotherapy,and standard&#xD;
             surgical treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  a history of non-standard treatment(chemotherapy or surgery)&#xD;
&#xD;
          -  secondary osteosarcoma or well-differentiated parosteal osteosarcoma&#xD;
&#xD;
          -  evident dysfunction of cardia,liver and kidney, or pregnant women or women during&#xD;
             lactation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jin Wang, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>First Affiliated Hospital, Sun Yat-Sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jin Wang, PhD</last_name>
    <phone>+86-20-87755766</phone>
    <phone_ext>8236</phone_ext>
    <email>2004wjhf@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>The first affiliated hospital,Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jin Wang, PhD</last_name>
      <phone>+86-20-87755766</phone>
      <phone_ext>8236</phone_ext>
      <email>2004wjhf@163.com;viewrine@qq.com</email>
    </contact>
    <investigator>
      <last_name>Jin Wang, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <last_update_submitted>October 31, 2016</last_update_submitted>
  <last_update_submitted_qc>October 31, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 1, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Jin Wang</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Lithium Carbonate</keyword>
  <keyword>Chemotherapy</keyword>
  <keyword>prognosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteosarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lithium Carbonate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Because our research has not yet finished, we would decide whether or not make individual participant data (IPD) available to other researchers according to the result of this study.</ipd_description>
  </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/NCT01669369
org study id: Lithium-5010
nct id: NCT01669369
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine whether Lithium Carbonate combined with
      neo-adjuvant chemotherapy improve the prognosis of osteosarcoma
Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence,
      the prognosis for the disease is poor. What's more, chemotherapy resistance and serious
      myelosuppression occur frequently in clinical further hindered canonical adjuvant
      chemotherapy. In our previous researches, we observed that GSK-3B positively regulates the
      NF-kB pathway to promote proliferation and tumorigenicity in osteosarcoma cell. Targeted
      inhibition of GSK3beta showed an obvious antitumor effect. It is a promising therapeutic
      target in osteosarcoma, especially if GSK-3b inhibition is combined with chemotherapeutic
      drugs. Lithium carbonate, commonly use in clinical application because of its fine quality
      and cheap price, was proven to be effected as a kind of GSK3beta inhibitor and stimulating
      factor of peripheral blood leukocyte. Therefore, lithium carbonate theoretically possesses
      effects of both anti-tumor as well as improvement of myelosuppression. We look forward to the
      results of clinical trials to test the effect of combinations of chemical drugs with lithium
      carbonate on myelosuppression, disease-free survival rate and lung metastasis rate in
      patients with osteosarcoma who treated with conventional chemotherapeutic regimens and wide
      resection. This study is a multi-centre, double-blind, randomized clinical trial phase 4. The
      inclusion criterion is patients with primary osteosarcoma in femur, tibia and humerus（IIB）.
      With the help of statistic method, 400 patients were randomly divided into two groups
      according to sequence of entering the group: lithium carbonate group and control group (1:1).
      Patients were suggesting continuing this trial until the end of the chemotherapy regimen or
      being confirmed as disease progression by RECIST guiding principles. According to their
      histological types, patients are analyzed using subgroup analysis. Disease evaluation will be
      conducted every 8 weeks. A follow-up to count the overall survival rate after grouping was
      performed within at least 24 months or at most 120 months. Our study may represent a novel
      and feasible approach by combination of conventional chemotherapy drugs and targeted drugs.
      More importantly, it may hopefully be a promising strategy to improve overall survival of
      osteosarcoma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: progression-free survival,incidence of chemotherapy-induced myelosuppression
time frame: at least 24 months or at most 120 months
measure: over-all survival,metastasis-free survival
time frame: at least 24 months or at most 120 months
arm group label: Placebo
arm group type: Placebo Comparator
description: The shape,color and smell of placebo are similar to Lithium Carbonate tablet used in the treatment arm.Patients in this arm take placebo twice a day.
arm group label: Lithium Carbonate
arm group type: Experimental
description: Patients in this arm take Lithium Carbonate twice a day with a dose of 20-25mg/kg/d.
intervention type: Drug
intervention name: Lithium Carbonate
description: 400 patients were randomly divided into two groups according to sequence of entering the group: lithium carbonate group and control group (1:1). Patients in lithium carbonate group were treated with combinations of chemotherapy and lithium carbonate, the control group were treated with chemotherapy only. Patients were suggesting continuing this trial until the end of the chemotherapy regimen or being confirmed as disease progression by RECIST.
arm group label: Lithium Carbonate
other name: Lithobid
intervention type: Drug
intervention name: Placebo
description: The shape,color and smell of placebo are similar to Lithium Carbonate tablet used in the treatment arm.Patients in this arm take placebo twice a day.
arm group label: Placebo
other name: PLACEBO TREATMENT
criteria: 
gender: All
minimum age: 8 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jin Wang, PhD
role: Principal Investigator
affiliation: First Affiliated Hospital, Sun Yat-Sen University
last name: Jin Wang, PhD
phone: +86-20-87755766
phone ext: 8236
email: 2004wjhf@163.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Jin Wang
investigator title: Professor
mesh term: Osteosarcoma
mesh term: Lithium Carbonate
sharing ipd: Undecided
ipd description: Because our research has not yet finished, we would decide whether or not make individual participant data (IPD) available to other researchers according to the result of this study.