<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/NCT03778996</url>
  </required_header>
  <id_info>
    <org_study_id>SM-88-JAF-16</org_study_id>
    <nct_id>NCT03778996</nct_id>
  </id_info>
  <brief_title>SM-88 Maintenance Therapy for Advanced Ewing's Sarcoma and as Salvage Therapy for Sarcoma</brief_title>
  <acronym>HopES</acronym>
  <official_title>Phase 2 Clinical Trial to Evaluate Efficacy and Safety of SM-88 Used With Methoxsalen, Phenytoin, and Sirolimus (MPS) as Maintenance Therapy Following Standard Treatments for Ewing's Sarcoma or as Salvage Therapy for Advanced Sarcomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sarcoma Oncology Research Center, LLC</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Tyme, Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sarcoma Oncology Research Center, LLC</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective is to evaluate the efficacy of SM-88, a combination metabolic cancer&#xD;
      treatment, in two study cohorts:&#xD;
&#xD;
        -  Clinically advanced Ewing's Sarcoma patients who have not progressed at the conclusion&#xD;
           of systemic treatment&#xD;
&#xD;
        -  Clinically advanced sarcoma patients in the salvage treatment setting&#xD;
&#xD;
      Up to 24 efficacy evaluable patients (up to 12 per cohort) will be enrolled. Study patients&#xD;
      will receive oral SM-88, with scheduled safety and efficacy evaluations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This prospective, open-label, two stage, pilot phase 2 trial evaluates the efficacy and&#xD;
      safety of SM-88 in two cohorts of patients: 1) as maintenance therapy following standard&#xD;
      primary or palliative treatments for Ewing's sarcoma patients with high risk of relapse or&#xD;
      disease progression; and 2) as salvage therapy for patients with clinically advanced&#xD;
      sarcomas.&#xD;
&#xD;
      The primary objective is to evaluate the efficacy of SM-88, a combination metabolic cancer&#xD;
      treatment, measured as positive efficacy events, including overall response, maintaining&#xD;
      stable disease for ≥ 3 months, or progression free survival at least 1.5 times longer than&#xD;
      the last prior line of treatment.&#xD;
&#xD;
      Eligible patients will receive daily oral treatment with SM-88, which consists of&#xD;
      D,L-alpha-metyrosine, used with methoxsalen, phenytoin, and sirolimus in continuous treatment&#xD;
      cycles of 28 days. Treatment will continue until: 1) Symptomatic, clinical progression with&#xD;
      radiographic progressive disease; 2) 48 weeks after documented complete response; or 3)&#xD;
      evidence of unacceptable toxicity, or other decision to discontinue treatment&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 3, 2020</start_date>
  <completion_date type="Anticipated">October 31, 2023</completion_date>
  <primary_completion_date type="Actual">January 19, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>Every 3 months for up to 2 years</time_frame>
    <description>Complete response (CR) + partial response (PR) as evaluated using RECIST 1.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Stable Disease for at Least 3 Months</measure>
    <time_frame>Every 3 months for up to 2 years</time_frame>
    <description>Stable disease (SD) as evaluated using RECIST 1.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival on Study of at Least 1.5 Times the Duration of PFS for the Last Prior Treatment</measure>
    <time_frame>Every 3 months for up to 2 years</time_frame>
    <description>From date of enrollment until the date of first documented progression, as evaluated using RECIST 1.1, or date of death, whichever occurs first</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>Every 3 months for up to 2 years</time_frame>
    <description>From date of CR or PR until the date of first documented progression, as evaluated using RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Every 3 months for up to 2 years</time_frame>
    <description>From date enrollment until the date of death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate</measure>
    <time_frame>Every 3 months for up to 2 years</time_frame>
    <description>CR+PR+SD as evaluated using RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5</measure>
    <time_frame>From date of enrollment until 28 days after last treatment with SM-88</time_frame>
    <description>Adverse events will be assessed at each visit and at unscheduled visits as clinically indicated</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Sarcoma, Ewing</condition>
  <condition>Sarcoma</condition>
  <arm_group>
    <arm_group_label>Maintenance Treatment: Ewing's Sarcoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Salvage Treatment: Sarcoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Combination metyrosine-derivative, low-dose methoxasalen, phenytoin and sirolimus</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)</intervention_name>
    <description>Daily oral combination therapy for cancer</description>
    <arm_group_label>Maintenance Treatment: Ewing's Sarcoma</arm_group_label>
    <arm_group_label>Salvage Treatment: Sarcoma</arm_group_label>
    <other_name>SM-88</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Ability to understand and willingness to provide written informed consent to&#xD;
             participate in this study&#xD;
&#xD;
          2. ≥12 years of age&#xD;
&#xD;
          3. Diagnosis:&#xD;
&#xD;
               1. Maintenance treatment cohort: Histologic or cytologic diagnosis of Ewing's&#xD;
                  sarcoma, including non-resected, locally advanced or metastatic disease&#xD;
&#xD;
               2. Salvage treatment cohort: Non-resected, locally advanced or metastatic sarcoma&#xD;
                  (including Ewing's sarcoma) for which there is no standard of care treatment and&#xD;
                  no curative other option&#xD;
&#xD;
          4. Radiographic disease assessment within 35 days prior to enrollment and planned&#xD;
             treatment start with study drug&#xD;
&#xD;
          5. Prior treatment:&#xD;
&#xD;
               1. Maintenance treatment cohort : 1-3 prior lines of systemic treatment (including&#xD;
                  current treatment)&#xD;
&#xD;
               2. Salvage cohort: Any number of prior treatments&#xD;
&#xD;
          6. Maintenance treatment cohort only: Patient completed current line of treatment&#xD;
             (systemic, surgery, radiation) prior to enrollment, without disease progression as&#xD;
             compared to baseline AND has achieved at least one of the following&#xD;
&#xD;
               1. CR in response to current second or third line treatment&#xD;
&#xD;
               2. PR in response to current line of treatment (after at least 4 cycles, if&#xD;
                  treatment included systemic therapy)&#xD;
&#xD;
               3. SD in response to current line of treatment (after at least 4 cycles, if&#xD;
                  treatment included systemic therapy)&#xD;
&#xD;
          7. Measurable disease, except for patients in Cohort A who have achieved CR at the&#xD;
             conclusion of current 2nd or 3rd line of treatment&#xD;
&#xD;
          8. ECOG performance status 0-2&#xD;
&#xD;
          9. Adequate organ function defined as all laboratory parameters ≤ Grade 2 NCI CTCAE&#xD;
             criteria&#xD;
&#xD;
         10. Patients must be able to swallow and retain whole capsules&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Systemic anticancer agents within 14 days prior to treatment on study&#xD;
&#xD;
          2. Major surgery within 30 days&#xD;
&#xD;
          3. Prior treatment with SM-88&#xD;
&#xD;
          4. Any screening laboratory, electrocardiogram (ECG), other clinical finding, comorbidity&#xD;
             or clinical history that, in the opinion of the investigator, indicates an&#xD;
             unacceptable risk for patient to participate in the study or would limit patient's&#xD;
             ability to comply with study requirements&#xD;
&#xD;
          5. History of any drug allergies or significant adverse reactions to any of the&#xD;
             components of SM-88&#xD;
&#xD;
          6. History of light sensitive diseases for which methoxsalen would be contraindicated&#xD;
&#xD;
          7. Current or anticipated treatment with a contraindicated medication&#xD;
&#xD;
          8. Evidence of viral infections including human immunodeficiency virus (HIV), hepatitis&#xD;
             B, and hepatitis C&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sant P Chawla, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sarcoma Oncology Research Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sarcoma Oncology Research Center</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://sarcomaoncology.com/</url>
    <description>Sarcoma Oncology Research Center</description>
  </link>
  <verification_date>January 2023</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 19, 2023</last_update_submitted>
  <last_update_submitted_qc>January 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ewing's Sarcoma</keyword>
  <keyword>Locally advanced sarcoma</keyword>
  <keyword>Metastatic sarcoma</keyword>
  <keyword>SM-88</keyword>
  <keyword>D.L-alpha-metyrosine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Sarcoma, Ewing</mesh_term>
    <mesh_term>Neuroectodermal Tumors, Primitive, Peripheral</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
    <mesh_term>Phenytoin</mesh_term>
    <mesh_term>Methoxsalen</mesh_term>
    <mesh_term>alpha-Methyltyrosine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03778996
org study id: SM-88-JAF-16
nct id: NCT03778996
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
The primary objective is to evaluate the efficacy of SM-88, a combination metabolic cancer
      treatment, in two study cohorts:

        -  Clinically advanced Ewing's Sarcoma patients who have not progressed at the conclusion
           of systemic treatment

        -  Clinically advanced sarcoma patients in the salvage treatment setting

      Up to 24 efficacy evaluable patients (up to 12 per cohort) will be enrolled. Study patients
      will receive oral SM-88, with scheduled safety and efficacy evaluations.
This prospective, open-label, two stage, pilot phase 2 trial evaluates the efficacy and
      safety of SM-88 in two cohorts of patients: 1) as maintenance therapy following standard
      primary or palliative treatments for Ewing's sarcoma patients with high risk of relapse or
      disease progression; and 2) as salvage therapy for patients with clinically advanced
      sarcomas.

      The primary objective is to evaluate the efficacy of SM-88, a combination metabolic cancer
      treatment, measured as positive efficacy events, including overall response, maintaining
      stable disease for ≥ 3 months, or progression free survival at least 1.5 times longer than
      the last prior line of treatment.

      Eligible patients will receive daily oral treatment with SM-88, which consists of
      D,L-alpha-metyrosine, used with methoxsalen, phenytoin, and sirolimus in continuous treatment
      cycles of 28 days. Treatment will continue until: 1) Symptomatic, clinical progression with
      radiographic progressive disease; 2) 48 weeks after documented complete response; or 3)
      evidence of unacceptable toxicity, or other decision to discontinue treatment
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate
time frame: Every 3 months for up to 2 years
description: Complete response (CR) + partial response (PR) as evaluated using RECIST 1.1
measure: Stable Disease for at Least 3 Months
time frame: Every 3 months for up to 2 years
description: Stable disease (SD) as evaluated using RECIST 1.1
measure: Progression Free Survival on Study of at Least 1.5 Times the Duration of PFS for the Last Prior Treatment
time frame: Every 3 months for up to 2 years
description: From date of enrollment until the date of first documented progression, as evaluated using RECIST 1.1, or date of death, whichever occurs first
measure: Duration of Response
time frame: Every 3 months for up to 2 years
description: From date of CR or PR until the date of first documented progression, as evaluated using RECIST 1.1
measure: Overall Survival
time frame: Every 3 months for up to 2 years
description: From date enrollment until the date of death
measure: Clinical Benefit Rate
time frame: Every 3 months for up to 2 years
description: CR+PR+SD as evaluated using RECIST 1.1
measure: Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5
time frame: From date of enrollment until 28 days after last treatment with SM-88
description: Adverse events will be assessed at each visit and at unscheduled visits as clinically indicated
arm group label: Maintenance Treatment: Ewing's Sarcoma
arm group type: Experimental
description: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus
arm group label: Salvage Treatment: Sarcoma
arm group type: Experimental
description: Combination metyrosine-derivative, low-dose methoxasalen, phenytoin and sirolimus
intervention type: Drug
intervention name: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)
description: Daily oral combination therapy for cancer
arm group label: Maintenance Treatment: Ewing's Sarcoma
arm group label: Salvage Treatment: Sarcoma
other name: SM-88
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Sant P Chawla, MD
role: Principal Investigator
affiliation: Sarcoma Oncology Research Center
facility: 
country: United States
url: https://sarcomaoncology.com/
description: Sarcoma Oncology Research Center
responsible party type: Sponsor
mesh term: Sarcoma
mesh term: Sarcoma, Ewing
mesh term: Neuroectodermal Tumors, Primitive, Peripheral
mesh term: Sirolimus
mesh term: Phenytoin
mesh term: Methoxsalen
mesh term: alpha-Methyltyrosine
sharing ipd: No