<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/NCT02993146</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2016-01909</org_study_id>
    <secondary_id>NCI-2016-01909</secondary_id>
    <secondary_id>HP-00067789</secondary_id>
    <secondary_id>9979</secondary_id>
    <secondary_id>9979</secondary_id>
    <secondary_id>UM1CA186686</secondary_id>
    <secondary_id>UM1CA186691</secondary_id>
    <nct_id>NCT02993146</nct_id>
  </id_info>
  <brief_title>Ropidoxuridine and Whole Brain Radiation Therapy in Treating Patients With Brain Metastases</brief_title>
  <official_title>Phase 1 and Pharmacology Study of Oral 5-Iodo-2-Pyrimidinone-2-Deoxyribose (IPdR) as a Prodrug for IUdR-Mediated Tumor Radiosensitization in Brain Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of ropidoxuridine when given&#xD;
      together with whole brain radiation therapy in treating patients with cancer that has spread&#xD;
      to the brain (brain metastases). Ropidoxuridine may help whole brain radiation therapy work&#xD;
      better by making cancer cells more sensitive to the radiation therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To conduct a phase 1 dose escalation trial in patients with brain metastases to determine&#xD;
      the recommended phase -2 dose of ropidoxuridine (5-iodo-2-pyrimidinone-2'-deoxyribose [IPdR])&#xD;
      when administered alone orally once daily for 7 consecutive days and then concurrently with&#xD;
      conventionally fractionated whole brain radiation therapy (WBRT) for additional 21 days.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To observe and record anti-tumor activity to IPdR-mediated radiosensitization.&#xD;
&#xD;
      II. To estimate 6 month intracranial progression-free survival (PFS) in brain metastasis&#xD;
      cancer patients who receive daily oral IPdR x 28 days and WBRT.&#xD;
&#xD;
      III. To establish the pharmacokinetics of daily oral dosing of IPdR times 8 days.&#xD;
&#xD;
      IV. To evaluate safety and tolerability of oral IPdR x 28 days and WBRT.&#xD;
&#xD;
      V. To estimate the incidence of delayed neurological toxicity at 2, 4, and 6 months (+/-1&#xD;
      week) post-completion of WBRT (for patients without intracranial progression) including:&#xD;
&#xD;
      Va. Delayed-recall through Hopkins Verbal Learning Test Revised (HVLT-R). Vb. Quality of life&#xD;
      as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-BR).&#xD;
&#xD;
      CORRELATIVE OBJECTIVES:&#xD;
&#xD;
      I. To assess for biochemical evidence of IPdR effect in normal tissues (circulating&#xD;
      granulocytes) by measuring %IUdR-deoxyribonucleic acid (DNA) cellular incorporation by flow&#xD;
      cytometry and high-pressure liquid chromatography (HPLC) analyses as an exploratory biomarker&#xD;
      for the following:&#xD;
&#xD;
      Ia. %IUdR-DNA tumor cell incorporation from day 8 extracranial tumor biopsies in brain&#xD;
      metastasis cancer patients receiving RP2D doses of IPdR as an exploratory biomarker of tumor&#xD;
      radiosensitization using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.&#xD;
&#xD;
      Ib. %IUdR-DNA cellular incorporation in patients' circulating granulocytes taken weekly&#xD;
      during the 28-day IPdR RP2D dose, on day 29, and week 8 as an exploratory biomarker of IPdR&#xD;
      systemic toxicities to bone marrow as measured by serial complete blood count&#xD;
      (CBC)/differential values.&#xD;
&#xD;
      OUTLINE: This is a dose escalation study of ropidoxuridine.&#xD;
&#xD;
      Patients receive ropidoxuridine orally (PO) once daily (QD) on days 1-28 and undergo WBRT&#xD;
      daily for not more than 5 days per week beginning on day 8 for a total of 15 fractions in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 2 months for 6 months,&#xD;
      every 3-4 months for 6 months, and every 6 months for 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 7, 2016</start_date>
  <completion_date type="Anticipated">February 24, 2024</completion_date>
  <primary_completion_date type="Actual">August 19, 2022</primary_completion_date>
  <phase>Phase 1</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>Maximum tolerated dose of ropidoxuridine</measure>
    <time_frame>Up to week 8</time_frame>
    <description>Will be defined as defined as the highest dose that has fewer than 3 (out of 6) patients experiencing dose-limiting toxicity assessed by National Cancer Institute's Common Toxicity Criteria version 4.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters of daily oral dosing of ropidoxuridine</measure>
    <time_frame>Pre-dose, 30, 60, 120, 240 minutes and 24 hours following oral dose administration on day 1 of course 1; pre-dose, 30, 60, 120, and 240 minutes following oral dose administration on days 15 and 22 of cycle 1</time_frame>
    <description>The pharmacokinetics of daily oral dosing of ropidoxuridine for 28 days will be explored.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers</measure>
    <time_frame>Up to week 8</time_frame>
    <description>Biomarker data will be explored in a simple descriptive manner.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intracranial progression free survival (icPFS)</measure>
    <time_frame>From the date of start of treatment to time of progression or death, whichever occurs first, assessed at 6 months</time_frame>
    <description>This will be explored using the Kaplan-Meier method. The icPFS estimates at 6 months with their standard error of the estimate will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Will be explored using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of delayed neurological toxicity including delayed-recall assessed by Hopkins Verbal Learning Test Revised (HVLT-R) and quality of life assessed by Functional Assessment of Cancer Therapy-Brain (FACT-BR)</measure>
    <time_frame>Up to 6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Hematopoietic and Lymphoid Cell Neoplasm</condition>
  <condition>Malignant Solid Neoplasm</condition>
  <condition>Metastatic Malignant Neoplasm in the Brain</condition>
  <arm_group>
    <arm_group_label>Treatment (ropidoxuridine, WBRT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ropidoxuridine PO QD on days 1-28 and undergo WBRT daily for not more than 5 days per week beginning on day 8 for a total of 15 fractions in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (ropidoxuridine, WBRT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (ropidoxuridine, WBRT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (ropidoxuridine, WBRT)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ropidoxuridine</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ropidoxuridine, WBRT)</arm_group_label>
    <other_name>5-Iodo-2-pyrimidinone 2' deoxyribonucleoside</other_name>
    <other_name>5-Iodo-2-pyrimidinone-2'-deoxyribose</other_name>
    <other_name>IPdR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Whole-Brain Radiotherapy</intervention_name>
    <description>Undergo WBRT</description>
    <arm_group_label>Treatment (ropidoxuridine, WBRT)</arm_group_label>
    <other_name>WBRT</other_name>
    <other_name>whole-brain radiation therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically confirmed malignancy with brain metastases and are&#xD;
             being recommended palliative WBRT&#xD;
&#xD;
          -  Life expectancy of greater than 2 months to allow completion of study treatment and&#xD;
             assessment of dose-limiting toxicity&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2 (Karnofsky &gt;= 60%)&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/mcL&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,000/mcL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  Calculated creatinine clearance &gt;= 45 mL/min/1.73 m^2&#xD;
&#xD;
          -  Total bilirubin:&#xD;
&#xD;
               -  If no known liver metastases: total bilirubin &lt; 1.5 x institutional upper limit&#xD;
                  of normal (ULN)&#xD;
&#xD;
               -  If known liver metastases, then: total bilirubin &lt; 2.5 x ULN&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and&#xD;
             alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]):&#xD;
&#xD;
               -  If no known liver metastases: AST/SGOT and ALT/SGPT both &lt; 2 x ULN&#xD;
&#xD;
               -  If known liver metastases, then: AST/SGOT and ALT/SGPT both &lt; 5 x ULN&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV) positive (+) patients with CD4 counts &gt;= 250&#xD;
             cells/mm^3 on anti-viral therapy are eligible for the study&#xD;
&#xD;
          -  Negative urine or serum pregnancy test result for females of child bearing potential&#xD;
             only; Note: The effects of IPdR on the developing human fetus are unknown; for this&#xD;
             reason and because radiation therapy is known to be teratogenic, women of&#xD;
             child-bearing potential and men must agree to use adequate contraception (hormonal or&#xD;
             barrier method of birth control; abstinence) prior to study entry and for the duration&#xD;
             of study participation; should a woman become pregnant or suspect she is pregnant&#xD;
             while she or her partner is participating in this study, she should inform her&#xD;
             treating physician immediately; men and women treated or enrolled on this protocol&#xD;
             must also agree to use adequate contraception prior to the study, for the duration of&#xD;
             study participation, and 4 months after completion of IPdR administration&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of diffuse lepto or pachy meningeal carcinomatosis (focal/localized&#xD;
             involvement from limited meningeal based metastases acceptable), greater than 1 cm&#xD;
             mid-line shift, uncal herniation, or severe hemorrhage/hydrocephalous (small&#xD;
             intra-lesional hemorrhage or anticipated surgical cavity is acceptable); patients with&#xD;
             seizure at presentation who have been started on levetiracetam and have been stable&#xD;
             for 48 hours prior to study registration are eligible at the discretion of treating&#xD;
             physician&#xD;
&#xD;
          -  Patients who have received systemic cytotoxic chemotherapy or approved oral targeted&#xD;
             therapy or immunotherapy for 2 weeks, or other investigational agents for 3 weeks (4&#xD;
             half-lives for any oral targeted agents), or radiotherapy to a non-brain site for 2&#xD;
             weeks before initiation of IPdR therapy; patients who have recovered from serious&#xD;
             (Common Terminology Criteria for Adverse Events [CTCAE] grade 3 or more higher) to&#xD;
             grade 1 or less adverse events from the previous therapies are eligible;&#xD;
             prior/current/future hormonal therapy and/or bisphosphonates are permitted with no&#xD;
             minimum interval to initiation of study therapy; if indicated, patients can receive&#xD;
             palliative radiation therapy to a non-brain site concurrent or immediately post-study&#xD;
             treatment with no minimum interval to initiation of study therapy&#xD;
&#xD;
          -  Patients must not have received prior whole brain radiation therapy; previous SRS/SRT&#xD;
             done at least 3 weeks from the planned start of IPdR therapy is acceptable;&#xD;
             SRS/SRT/fractionated boosts or neurosurgery can be performed once the dose limiting&#xD;
             toxicity (DLT) assessment has been completed, if felt clinically necessary&#xD;
&#xD;
          -  Patients with primary tumors including germ cell tumor, or lymphoma/leukemia&#xD;
&#xD;
          -  Patients who are receiving any other investigational agent&#xD;
&#xD;
          -  Patients needing more than 8 mg dexamethasone per day at the time of start of WBRT&#xD;
             will not be eligible to participate in the study; however, patients will be allowed&#xD;
             entry into the study if it is medically safe to reduce the daily dose of dexamethasone&#xD;
             to 8 mg or less from the day of the start of WBRT; the dexamethasone dose for such&#xD;
             patients may be increased beyond 8 mg per day during the course of treatment if&#xD;
             medically necessary; this increased need for dose should be communicated to the&#xD;
             study's principal investigator, Dr Mohindra at the University of Maryland&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to IPdR&#xD;
&#xD;
          -  Uncontrolled intercurrent illness if it would increase the risk of toxicity or limit&#xD;
             compliance with study requirements; this includes, but is not limited to, ongoing&#xD;
             uncontrolled serious infection requiring intravenous (i.v.) antibiotics, progressive&#xD;
             congestive heart failure, unstable angina pectoris, or psychiatric illness/social&#xD;
             situations that would limit compliance with study requirements&#xD;
&#xD;
          -  Pregnant women are excluded from this study because IPdR is an agent with the&#xD;
             potential for teratogenic or abortifacient effects; because there is an unknown but&#xD;
             potential risk for adverse events in nursing infants secondary to treatment of the&#xD;
             mother with IPdR, breastfeeding should be discontinued if the mother is treated with&#xD;
             IPdR&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pranshu Mohindra</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic Cancer Center LAO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UC San Diego Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa/Holden Comprehensive Cancer Center</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland/Greenebaum Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wayne State University/Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weisberg Cancer Treatment Center</name>
      <address>
        <city>Farmington Hills</city>
        <state>Michigan</state>
        <zip>48334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern/Simmons Cancer Center-Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ben Taub General Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute/University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 14, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>February 25, 2023</last_update_submitted>
  <last_update_submitted_qc>February 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 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>
    <mesh_term>Brain Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ropidoxuridine</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/NCT02993146
org study id: NCI-2016-01909
secondary id: NCI-2016-01909
secondary id: HP-00067789
secondary id: 9979
secondary id: 9979
secondary id: UM1CA186686
secondary id: UM1CA186691
nct id: NCT02993146
lead sponsor: 
has dmc: Yes
This phase I trial studies the side effects and best dose of ropidoxuridine when given
      together with whole brain radiation therapy in treating patients with cancer that has spread
      to the brain (brain metastases). Ropidoxuridine may help whole brain radiation therapy work
      better by making cancer cells more sensitive to the radiation therapy.
PRIMARY OBJECTIVE:

      I. To conduct a phase 1 dose escalation trial in patients with brain metastases to determine
      the recommended phase -2 dose of ropidoxuridine (5-iodo-2-pyrimidinone-2'-deoxyribose [IPdR])
      when administered alone orally once daily for 7 consecutive days and then concurrently with
      conventionally fractionated whole brain radiation therapy (WBRT) for additional 21 days.

      SECONDARY OBJECTIVES:

      I. To observe and record anti-tumor activity to IPdR-mediated radiosensitization.

      II. To estimate 6 month intracranial progression-free survival (PFS) in brain metastasis
      cancer patients who receive daily oral IPdR x 28 days and WBRT.

      III. To establish the pharmacokinetics of daily oral dosing of IPdR times 8 days.

      IV. To evaluate safety and tolerability of oral IPdR x 28 days and WBRT.

      V. To estimate the incidence of delayed neurological toxicity at 2, 4, and 6 months (+/-1
      week) post-completion of WBRT (for patients without intracranial progression) including:

      Va. Delayed-recall through Hopkins Verbal Learning Test Revised (HVLT-R). Vb. Quality of life
      as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-BR).

      CORRELATIVE OBJECTIVES:

      I. To assess for biochemical evidence of IPdR effect in normal tissues (circulating
      granulocytes) by measuring %IUdR-deoxyribonucleic acid (DNA) cellular incorporation by flow
      cytometry and high-pressure liquid chromatography (HPLC) analyses as an exploratory biomarker
      for the following:

      Ia. %IUdR-DNA tumor cell incorporation from day 8 extracranial tumor biopsies in brain
      metastasis cancer patients receiving RP2D doses of IPdR as an exploratory biomarker of tumor
      radiosensitization using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

      Ib. %IUdR-DNA cellular incorporation in patients' circulating granulocytes taken weekly
      during the 28-day IPdR RP2D dose, on day 29, and week 8 as an exploratory biomarker of IPdR
      systemic toxicities to bone marrow as measured by serial complete blood count
      (CBC)/differential values.

      OUTLINE: This is a dose escalation study of ropidoxuridine.

      Patients receive ropidoxuridine orally (PO) once daily (QD) on days 1-28 and undergo WBRT
      daily for not more than 5 days per week beginning on day 8 for a total of 15 fractions in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 2 months for 6 months,
      every 3-4 months for 6 months, and every 6 months for 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose of ropidoxuridine
time frame: Up to week 8
description: Will be defined as defined as the highest dose that has fewer than 3 (out of 6) patients experiencing dose-limiting toxicity assessed by National Cancer Institute's Common Toxicity Criteria version 4.
measure: Tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1
time frame: Up to 2 years
description: Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).
measure: Pharmacokinetic parameters of daily oral dosing of ropidoxuridine
time frame: Pre-dose, 30, 60, 120, 240 minutes and 24 hours following oral dose administration on day 1 of course 1; pre-dose, 30, 60, 120, and 240 minutes following oral dose administration on days 15 and 22 of cycle 1
description: The pharmacokinetics of daily oral dosing of ropidoxuridine for 28 days will be explored.
measure: Biomarkers
time frame: Up to week 8
description: Biomarker data will be explored in a simple descriptive manner.
measure: Intracranial progression free survival (icPFS)
time frame: From the date of start of treatment to time of progression or death, whichever occurs first, assessed at 6 months
description: This will be explored using the Kaplan-Meier method. The icPFS estimates at 6 months with their standard error of the estimate will be reported.
measure: Overall survival
time frame: Up to 2 years
description: Will be explored using the Kaplan-Meier method.
measure: Incidence of delayed neurological toxicity including delayed-recall assessed by Hopkins Verbal Learning Test Revised (HVLT-R) and quality of life assessed by Functional Assessment of Cancer Therapy-Brain (FACT-BR)
time frame: Up to 6 months
arm group label: Treatment (ropidoxuridine, WBRT)
arm group type: Experimental
description: Patients receive ropidoxuridine PO QD on days 1-28 and undergo WBRT daily for not more than 5 days per week beginning on day 8 for a total of 15 fractions in the absence of disease progression or unacceptable toxicity.
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (ropidoxuridine, WBRT)
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Treatment (ropidoxuridine, WBRT)
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Treatment (ropidoxuridine, WBRT)
other name: Quality of Life Assessment
intervention type: Drug
intervention name: Ropidoxuridine
description: Given PO
arm group label: Treatment (ropidoxuridine, WBRT)
other name: 5-Iodo-2-pyrimidinone 2' deoxyribonucleoside
other name: 5-Iodo-2-pyrimidinone-2'-deoxyribose
other name: IPdR
intervention type: Radiation
intervention name: Whole-Brain Radiotherapy
description: Undergo WBRT
arm group label: Treatment (ropidoxuridine, WBRT)
other name: WBRT
other name: whole-brain radiation therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pranshu Mohindra
role: Principal Investigator
affiliation: Mayo Clinic Cancer Center LAO
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country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Brain Neoplasms
mesh term: Ropidoxuridine