<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/NCT01716689</url>
  </required_header>
  <id_info>
    <org_study_id>NCC1201</org_study_id>
    <nct_id>NCT01716689</nct_id>
  </id_info>
  <brief_title>Clinical Study of Metronomic Oral Cyclophosphamide in Patients With Advanced Sarcomas</brief_title>
  <official_title>Phase II Clinical Study of Metronomic Oral Cyclophosphamide in Elderly and/or Pre-treated Patients With Advanced Sarcomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Centre, Singapore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Centre, Singapore</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single arm phase II clinical study to evaluate the efficacy and safety of&#xD;
      metronomic oral cyclophosphamide in elderly and/or pre-treated patients with advanced&#xD;
      sarcomas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible patients will receive continuous metronomic oral cyclophosphamide at a dose of 50mg&#xD;
      daily. Tumor assessments will be performed at baseline and every 6 weeks thereafter to assess&#xD;
      response and disease progression. Toxicity will be monitored throughout treatment. The&#xD;
      study's primary end point is defined as clinical benefit rate (CBR) at 12 weeks as a measure&#xD;
      of disease control. The study is designed to distinguish a favorable true PFR of 40% from a&#xD;
      null rate of 20% [Van Glabbeke et al. EJC 2002]. With a CBR of 40%, metronomic oral&#xD;
      cyclophosphamide at this dose and schedule in this patient population will be considered&#xD;
      worthy of further evaluation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2012</start_date>
  <completion_date type="Actual">October 2016</completion_date>
  <primary_completion_date type="Actual">October 2016</primary_completion_date>
  <phase>Phase 2</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>Clinical benefit as defined by the composite of complete response (CR), partial response (PR) and stable disease (SD) lasting &gt; 12 weeks per RECIST 1.1 as a measure of disease control</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of objective response rate (ORR)</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of progression free survival</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment on duration of response to oral metronomic cyclophosphamide in patients who exhibit objective responses</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Sarcoma</condition>
  <arm_group>
    <arm_group_label>Patients with advanced sarcoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oral cyclophosphamide</intervention_name>
    <description>50mg daily</description>
    <arm_group_label>Patients with advanced sarcoma</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Participants must meet the following criteria on screening examination to be eligible to&#xD;
        participate in the study:&#xD;
&#xD;
          1. Participants must have histologically or cytologically confirmed, metastatic and/or&#xD;
             unresectable high grade sarcoma for which standard multi-modality curative therapies&#xD;
             do not exist or are no longer effective. Patients with low grade sarcoma need to&#xD;
             additionally demonstrate disease progression in the last 6 months prior to study&#xD;
             entry.&#xD;
&#xD;
          2. Age &gt; 21 years&#xD;
&#xD;
          3. Prior anti-sarcoma chemotherapy&#xD;
&#xD;
               -  Participants who are 21 to 64 years of age at the time of study entry must have&#xD;
                  received at least one line of established chemotherapy, if such treatment exists;&#xD;
                  or refused such treatment, which includes either an anthracycline and/or&#xD;
                  ifosfamide. Patients whose sarcomas do not have known established therapy are&#xD;
                  eligible for this study without the requirement of a prior therapy.&#xD;
&#xD;
               -  Participants &gt; 65 years of age at the time of study entry are eligible for this&#xD;
                  study without the requirement for prior treatment&#xD;
&#xD;
          4. ECOG performance status 0-3 (see Annex A)&#xD;
&#xD;
          5. Measurable disease outside of a prior irradiated area as defined by RECIST 1.1&#xD;
             guidelines. A lesion in a previously irradiated area is not eligible for measurable&#xD;
             disease unless there is objective evidence of progression of the lesion prior to study&#xD;
             enrollment&#xD;
&#xD;
          6. No limit to number of prior chemotherapies or biologics&#xD;
&#xD;
          7. Participants must have normal organ function as defined below:&#xD;
&#xD;
               -  Hemoglobin &gt; 10g/dL&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &gt; 1500/mm3&#xD;
&#xD;
               -  Platelet count &gt; 75,000/mm3&#xD;
&#xD;
               -  Total bilirubin &lt; 1.5 times institutional upper limits or normal (ULN)&#xD;
&#xD;
               -  AST/ALT &lt; 3 times ULN (&lt; 5 times ULN if hepatic involvement is present)&#xD;
&#xD;
               -  Creatinine &lt; 1.5 times ULN. If creatinine is &gt; 1.5 times ULN, a calculated&#xD;
                  creatinine clearance time (CCT) should be performed and patient would be eligible&#xD;
                  for study if the calculated CCT is &gt; 10 mL/min.&#xD;
&#xD;
             [NB: Glomerular filtration rate (GFR) = [(140 - age) x weight [kg] x 1.22 ] / (serum&#xD;
             creatinine [umol/L]. In women, multiply this result by 0.85&#xD;
&#xD;
          8. Resolution, or return to baseline of all clinically significant toxicities related to&#xD;
             prior therapies&#xD;
&#xD;
          9. Patients must be suitable for oral drug administration&#xD;
&#xD;
         10. Willingness to use effective means of birth control throughout the duration of&#xD;
             clinical study and for at least 3 months after completion of study drug&#xD;
&#xD;
         11. Women of childbearing potential must have a negative pregnancy test performed within 7&#xD;
             days of the start of study drug administration&#xD;
&#xD;
         12. Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Participants who exhibit any of the following conditions at screening will not be eligible&#xD;
        for admission into the study.&#xD;
&#xD;
          1. Patients diagnosed with gastrointestinal stromal tumor (GIST)&#xD;
&#xD;
          2. Participants who have had systemic anti-cancer therapy within 3 weeks of study entry&#xD;
             (8 weeks for nitrosoureas or mitomycin C)&#xD;
&#xD;
          3. Palliative radiotherapy or major surgery within 3 weeks of study entry&#xD;
&#xD;
          4. Concurrent use of any other anti-cancer therapies or study agents&#xD;
&#xD;
          5. Symptomatic or uncontrolled brain or central nervous system metastases&#xD;
&#xD;
          6. Participants may not be receiving any other concomitant investigational agents&#xD;
&#xD;
          7. Uncontrolled intercurrent illness including, but not limited to ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          8. Individuals with a history of a different malignancy, other than cervical cancer in&#xD;
             situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if&#xD;
             they have been disease-free for at least 5 years, and are deemed by the investigator&#xD;
             to be at low risk for recurrence of that malignancy OR other primary malignancy is&#xD;
             neither currently clinically significant nor requiring active intervention.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Quek</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Centre, Singapore</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Cancer Centre Singapore</name>
      <address>
        <city>Singapore</city>
        <zip>169610</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>May 13, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <last_update_submitted>March 27, 2017</last_update_submitted>
  <last_update_submitted_qc>March 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</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/NCT01716689
org study id: NCC1201
nct id: NCT01716689
lead sponsor: 
has dmc: No
This is a single arm phase II clinical study to evaluate the efficacy and safety of
      metronomic oral cyclophosphamide in elderly and/or pre-treated patients with advanced
      sarcomas.
Eligible patients will receive continuous metronomic oral cyclophosphamide at a dose of 50mg
      daily. Tumor assessments will be performed at baseline and every 6 weeks thereafter to assess
      response and disease progression. Toxicity will be monitored throughout treatment. The
      study's primary end point is defined as clinical benefit rate (CBR) at 12 weeks as a measure
      of disease control. The study is designed to distinguish a favorable true PFR of 40% from a
      null rate of 20% [Van Glabbeke et al. EJC 2002]. With a CBR of 40%, metronomic oral
      cyclophosphamide at this dose and schedule in this patient population will be considered
      worthy of further evaluation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical benefit as defined by the composite of complete response (CR), partial response (PR) and stable disease (SD) lasting > 12 weeks per RECIST 1.1 as a measure of disease control
time frame: 24 months
measure: Assessment of objective response rate (ORR)
time frame: 24 months
measure: Assessment of progression free survival
time frame: 24 months
measure: Assessment on duration of response to oral metronomic cyclophosphamide in patients who exhibit objective responses
time frame: 24 months
arm group label: Patients with advanced sarcoma
arm group type: Experimental
intervention type: Drug
intervention name: oral cyclophosphamide
description: 50mg daily
arm group label: Patients with advanced sarcoma
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Richard Quek
role: Principal Investigator
affiliation: National Cancer Centre, Singapore
facility: 
country: Singapore
responsible party type: Sponsor
mesh term: Sarcoma
mesh term: Cyclophosphamide