xml: <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/NCT06006273</url>
    </required_header>
    <id_info>
      <org_study_id>2023-0163</org_study_id>
      <secondary_id>NCI-2023-06570</secondary_id>
      <nct_id>NCT06006273</nct_id>
    </id_info>
    <brief_title>A Phase Ib Trial of Eribulin in Combination With Irinotecan and Temozolamide in Children With Relapsed or Refractory Solid Tumors</brief_title>
    <official_title>A Phase Ib Trial of Eribulin in Combination With Irinotecan and Temozolamide in Children With Relapsed or Refractory Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>M.D. Anderson Cancer Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>M.D. Anderson Cancer Center</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        To find the recommended dose of eribulin that can be given in combination with irinotecan and&#xD;
        temozolomide to treat relapsed and/or refractory solid tumors.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Primary Objectives:&#xD;
  &#xD;
          -  To determine the maximum tolerated dose (MTD)/ recommended phase 2 dose (RP2D) of&#xD;
             eribulin in combination with fixed doses of irinotecan and temozolomide.&#xD;
  &#xD;
          -  To determine the safety and tolerance of Eribulin when given in conjunction with&#xD;
             Irinotecan and Temozolamide (IT) in children with refractory and relapsed (R/R) solid&#xD;
             tumors.&#xD;
  &#xD;
        Secondary Objectives:&#xD;
  &#xD;
        --To observe and record disease response (anti-tumor activity). Although the clinical benefit&#xD;
        of Eribulin when given together with Irinotecan and Temozolamide has not yet been&#xD;
        established, the intent of offering this treatment is to provide a possible therapeutic&#xD;
        benefit, and thus the patient will be carefully monitored for tumor response and symptom&#xD;
        relief. Outcomes for disease response include Best Overall Response (BOR), Duration of&#xD;
        Response (DOR), and Progression-Free Survival (PFS).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 16, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2028</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2026</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0</measure>
      <time_frame>through study completion; an average of 1 year</time_frame>
    </primary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">48</enrollment>
    <condition>Refractory Solid Tumors</condition>
    <arm_group>
      <arm_group_label>Arm A: Dose expansion-Ewings sarcoma</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The first group of participants in this phase will receive the highest dose of eribulin. Each group of participants enrolled after that will receive a slightly lower dose of the drug. Participants in this phase will be enrolled in 1 of 3 treatment arms, based on their disease type, and will receive the recommended dose combination found in the Dose Escalation phase.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm B: Dose expansion -Rhabdomyosarcoma</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The first group of participants in this phase will receive the highest dose of eribulin. Each group of participants enrolled after that will receive a slightly lower dose of the drug. Participants in this phase will be enrolled in 1 of 3 treatment arms, based on their disease type, and will receive the recommended dose combination found in the Dose Escalation phase.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm C: Dose expansion- other solid tumor histologies</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The first group of participants in this phase will receive the highest dose of eribulin. Each group of participants enrolled after that will receive a slightly lower dose of the drug. Participants in this phase will be enrolled in 1 of 3 treatment arms, based on their disease type, and will receive the recommended dose combination found in the Dose Escalation phase.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm D: Dose finding levels 0,-1 and -2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The first group of participants in this phase will receive the highest dose of eribulin. Each group of participants enrolled after that will receive a slightly lower dose of the drug. Participants in this phase will be enrolled in 1 of 3 treatment arms, based on their disease type, and will receive the recommended dose combination found in the Dose Escalation phase.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Eribulin</intervention_name>
      <description>Given by vein (IV)</description>
      <arm_group_label>Arm A: Dose expansion-Ewings sarcoma</arm_group_label>
      <arm_group_label>Arm B: Dose expansion -Rhabdomyosarcoma</arm_group_label>
      <arm_group_label>Arm C: Dose expansion- other solid tumor histologies</arm_group_label>
      <arm_group_label>Arm D: Dose finding levels 0,-1 and -2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Irinotecan</intervention_name>
      <description>Given by vein (IV)</description>
      <arm_group_label>Arm A: Dose expansion-Ewings sarcoma</arm_group_label>
      <arm_group_label>Arm B: Dose expansion -Rhabdomyosarcoma</arm_group_label>
      <arm_group_label>Arm C: Dose expansion- other solid tumor histologies</arm_group_label>
      <arm_group_label>Arm D: Dose finding levels 0,-1 and -2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Temozolomide</intervention_name>
      <description>Given by PO</description>
      <arm_group_label>Arm A: Dose expansion-Ewings sarcoma</arm_group_label>
      <arm_group_label>Arm B: Dose expansion -Rhabdomyosarcoma</arm_group_label>
      <arm_group_label>Arm C: Dose expansion- other solid tumor histologies</arm_group_label>
      <arm_group_label>Arm D: Dose finding levels 0,-1 and -2</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age: Patients must be &gt; 1 year of age and ≤ 25 years of age at time of initiation of&#xD;
               protocol therapy.&#xD;
  &#xD;
            -  Diagnosis: Patients have a histologically or radiographically confirmed relapsed or&#xD;
               refractory solid tumor.&#xD;
  &#xD;
            -  Disease Status: Patients must have evaluable disease.&#xD;
  &#xD;
            -  Patients may have CNS metastases at study entry, if they are previously treated or&#xD;
               stable (defined by not requiring initation or increased steroids for 7 days).&#xD;
  &#xD;
            -  Performance Level: Karnofsky ≥ 50% for patients &gt;16 years old, and Lansky ≥ 50 for&#xD;
               patients 1-16 years old. (Appendix I)&#xD;
  &#xD;
            -  Prior Therapy: Patients may have received prior therapy including single-agent&#xD;
               irinotecan or temozolomide. Patients may not have previously been treated with&#xD;
               combination therapy of irinotecan and temozolomide.&#xD;
  &#xD;
            -  Patients must be fully recovered from the acute toxic effects of all prior&#xD;
               chemotherapy, immunotherapy, or radiotherapy prior to entering this study.&#xD;
  &#xD;
                 1. Hematopoietic growth factor: At least 7 days must have elapsed since the last&#xD;
                    administration of filgrastim, or 14 days since administration of pegfilgrastim.&#xD;
  &#xD;
                 2. XRT: At least 7 days since the last dose of local palliative radiation therapy.&#xD;
                    Greater than 6 months must have elapsed since the last day of treatment if given&#xD;
                    total body irradiation, craniospinal irradiation.&#xD;
  &#xD;
                 3. Autologous or Allogenic Stem Cell Transplant: Complete resolution of graft versus&#xD;
                    host disease and no current need for immunosuppressive medication. Greater than 3&#xD;
                    months must have elapsed since engraftment and no longer requiring transfusion of&#xD;
                    platelets or injection of colony stimulating factors.&#xD;
  &#xD;
                      -  Organ Function Requirements&#xD;
  &#xD;
            -  Bone Marrow Function:&#xD;
  &#xD;
                 1. Peripheral absolute neutrophil count (ANC) ≥ 750/µL&#xD;
  &#xD;
                 2. Platelet count ≥ 75,000/µL (no platelet transfusion within 7 days prior to&#xD;
                    obtaining laboratory result)&#xD;
  &#xD;
            -  Adequate Renal Function:&#xD;
  &#xD;
               a. Creatinine clearance or glomerular filtration rate ≥ 70ml/min/1.73m2 (calculated or&#xD;
               measured as appropriate for age and level of concern by treating MD)&#xD;
  &#xD;
            -  Adequate Liver Function:&#xD;
  &#xD;
                 1. Total bilirubin ≤ 1.5x upper limit of normal (ULN) for age&#xD;
  &#xD;
                 2. SGPT (ALT) ≤ 3 x ULN&#xD;
  &#xD;
                 3. Serum albumin ≥ 2gm/dL Due to the risk of hepatic injury, including fatal hepatic&#xD;
                    failure, temozolomide should not be administered if total bilirubin is &gt;2.0 mg/dl&#xD;
                    or SGPT(ALT)&gt; 3 x ULN.&#xD;
  &#xD;
          Informed Consent: All patients ≥ 18 years of age must sign a written informed consent. For&#xD;
          patients &lt; 18 years old, the patient's parents or legal guardians must sign a written&#xD;
          informed consent, unless the patient is an emancipated minor. Childhood Assent, when age&#xD;
          appropriate as per institutional guidelines, should be signed by the participating patient.&#xD;
          Consent may be obtained virtually, as per institutional guidelines.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Significant organ dysfunction, not meeting inclusion criteria.&#xD;
  &#xD;
            -  Pediatric subjects who are considered wards of some entity&#xD;
  &#xD;
            -  Pregnancy or Breast-Feeding&#xD;
  &#xD;
            -  Pregnant or breast-feeding woman will not be entered on this study due to risks of&#xD;
               fetal and teratogenic adverse events as seen in animal/human studies.&#xD;
  &#xD;
            -  Concomitant Medications:&#xD;
  &#xD;
            -  Growth factor: Growth factors that support platelet or white cell number of function&#xD;
               must not have been administered within the past 7 days.&#xD;
  &#xD;
            -  Investigational Drugs: Patients who are currently receiving another investigational&#xD;
               drug. (Please refer to Prior Therapy, section 2.1.5)&#xD;
  &#xD;
            -  Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents.&#xD;
               (Please refer to Prior Therapy, section 2.1.5.1)&#xD;
  &#xD;
            -  Medication Allergy:&#xD;
  &#xD;
                 1. Allergy or intolerance to agents on this protocol: irinotecan, temozolomide, or&#xD;
                    eribuin&#xD;
  &#xD;
                 2. Allergy to cephalosporins, without a reasonably available antibiotic alternative&#xD;
  &#xD;
            -  Infection: Patients who have uncontrolled infection, positive blood cultures within&#xD;
               the past 48 hours, or receiving treatment for Clostridium difficile infection.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Year</minimum_age>
      <maximum_age>25 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Fiorela Hernandez Tejada, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>M.D. Anderson Cancer Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Fiorela Hernandez Tejada, MD</last_name>
      <phone>(832) 306-9802</phone>
      <email>fnhernandez@mdanderson.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>M D Anderson Cancer Center</name>
        <address>
          <city>Houston</city>
          <state>Texas</state>
          <zip>77030</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Fiorela Hernandez Tejada, MD</last_name>
        <phone>832-306-9802</phone>
        <email>fnhernandez@mdanderson.org</email>
      </contact>
      <investigator>
        <last_name>Fiorela Hernandez Tejada, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>http://www.mdanderson.org</url>
      <description>M D Anderson Cancer Center</description>
    </link>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</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>Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Irinotecan</mesh_term>
      <mesh_term>Temozolomide</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06006273
  org study id: 2023-0163
  secondary id: NCI-2023-06570
  nct id: NCT06006273
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  To find the recommended dose of eribulin that can be given in combination with irinotecan and
        temozolomide to treat relapsed and/or refractory solid tumors.
  Primary Objectives:
  
          -  To determine the maximum tolerated dose (MTD)/ recommended phase 2 dose (RP2D) of
             eribulin in combination with fixed doses of irinotecan and temozolomide.
  
          -  To determine the safety and tolerance of Eribulin when given in conjunction with
             Irinotecan and Temozolamide (IT) in children with refractory and relapsed (R/R) solid
             tumors.
  
        Secondary Objectives:
  
        --To observe and record disease response (anti-tumor activity). Although the clinical benefit
        of Eribulin when given together with Irinotecan and Temozolamide has not yet been
        established, the intent of offering this treatment is to provide a possible therapeutic
        benefit, and thus the patient will be carefully monitored for tumor response and symptom
        relief. Outcomes for disease response include Best Overall Response (BOR), Duration of
        Response (DOR), and Progression-Free Survival (PFS).
  allocation: Randomized
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
  time frame: through study completion; an average of 1 year
  arm group label: Arm A: Dose expansion-Ewings sarcoma
  arm group type: Experimental
  description: The first group of participants in this phase will receive the highest dose of eribulin. Each group of participants enrolled after that will receive a slightly lower dose of the drug. Participants in this phase will be enrolled in 1 of 3 treatment arms, based on their disease type, and will receive the recommended dose combination found in the Dose Escalation phase.
  arm group label: Arm B: Dose expansion -Rhabdomyosarcoma
  arm group type: Experimental
  description: The first group of participants in this phase will receive the highest dose of eribulin. Each group of participants enrolled after that will receive a slightly lower dose of the drug. Participants in this phase will be enrolled in 1 of 3 treatment arms, based on their disease type, and will receive the recommended dose combination found in the Dose Escalation phase.
  arm group label: Arm C: Dose expansion- other solid tumor histologies
  arm group type: Experimental
  description: The first group of participants in this phase will receive the highest dose of eribulin. Each group of participants enrolled after that will receive a slightly lower dose of the drug. Participants in this phase will be enrolled in 1 of 3 treatment arms, based on their disease type, and will receive the recommended dose combination found in the Dose Escalation phase.
  arm group label: Arm D: Dose finding levels 0,-1 and -2
  arm group type: Experimental
  description: The first group of participants in this phase will receive the highest dose of eribulin. Each group of participants enrolled after that will receive a slightly lower dose of the drug. Participants in this phase will be enrolled in 1 of 3 treatment arms, based on their disease type, and will receive the recommended dose combination found in the Dose Escalation phase.
  intervention type: Drug
  intervention name: Eribulin
  description: Given by vein (IV)
  arm group label: Arm A: Dose expansion-Ewings sarcoma
  arm group label: Arm B: Dose expansion -Rhabdomyosarcoma
  arm group label: Arm C: Dose expansion- other solid tumor histologies
  arm group label: Arm D: Dose finding levels 0,-1 and -2
  intervention type: Drug
  intervention name: Irinotecan
  description: Given by vein (IV)
  arm group label: Arm A: Dose expansion-Ewings sarcoma
  arm group label: Arm B: Dose expansion -Rhabdomyosarcoma
  arm group label: Arm C: Dose expansion- other solid tumor histologies
  arm group label: Arm D: Dose finding levels 0,-1 and -2
  intervention type: Drug
  intervention name: Temozolomide
  description: Given by PO
  arm group label: Arm A: Dose expansion-Ewings sarcoma
  arm group label: Arm B: Dose expansion -Rhabdomyosarcoma
  arm group label: Arm C: Dose expansion- other solid tumor histologies
  arm group label: Arm D: Dose finding levels 0,-1 and -2
  criteria: 
  gender: All
  minimum age: 1 Year
  maximum age: 25 Years
  healthy volunteers: No
  last name: Fiorela Hernandez Tejada, MD
  role: Principal Investigator
  affiliation: M.D. Anderson Cancer Center
  last name: Fiorela Hernandez Tejada, MD
  phone: (832) 306-9802
  email: fnhernandez@mdanderson.org
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: United States
  url: http://www.mdanderson.org
  description: M D Anderson Cancer Center
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Irinotecan
  mesh term: Temozolomide