<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/NCT02199236</url>
  </required_header>
  <id_info>
    <org_study_id>14-104</org_study_id>
    <nct_id>NCT02199236</nct_id>
  </id_info>
  <brief_title>Dose Escalation Trial of Endoluminal High-Dose-Rate Brachytherapy With Concurrent Chemotherapy for Rectal or Anal Cancer in Patients With Recurrent Disease or Undergoing Non-Operative Management</brief_title>
  <official_title>A Phase I, Dose Escalation Trial of Endoluminal High Dose Rate Brachytherapy With Concurrent Chemotherapy for Rectal or Anal Cancer in Patients With Recurrent Disease or Undergoing Non-Operative Management</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to see what amount of radiation is safe to give to rectal or&#xD;
      anal cancer patients who are being treated with a procedure called brachytherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">July 2024</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 (MTD)</measure>
    <time_frame>1 year</time_frame>
    <description>will employ a standard 3+3 dose-escalation scheme. Patients will be accrued to the study in cohorts of 3. An initial cohort of 3 patients will be treated to each dose. The dose level will be escalated if none of the 3 patients exhibits any DLT within 90 days of completion of brachytherapy. Dose escalation will not take place until every patient in the prior dose cohort has been monitored for 90 days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>tumor response</measure>
    <time_frame>3, 6, and 12 months</time_frame>
    <description>MRI with DCE &amp; DWI (unless contraindicated) after brachytherapy</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Rectal or Anal Cancer</condition>
  <arm_group>
    <arm_group_label>endorectal brachytherapy, concurrent chemo and questionnaires</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This is a phase I, dose-escalation study to evaluate the safety of endorectal brachytherapy with concurrent capecitabine or 5-fluoruracil (5-FU) in the management of locally recurrent/residual rectal or anal cancer in patients who have received pelvic external beam radiation therapy (EBRT) +/- chemotherapy. We will use magnetic resonance imaging (MRI) with dynamic contrast enhancement (DCE) and diffusion weighted imaging (DWI) series to contribute to the assessment of tumor response.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>endorectal brachytherapy</intervention_name>
    <description>Patients will receive 3 fractions of endorectal brachytherapy, each spaced apart by 7 days (+/- 1 day). The three dose tiers will be 1500cGy (500cGy per fraction), 1800cGy (600cGy per fraction), and 2100cGy (700cGy per fraction).</description>
    <arm_group_label>endorectal brachytherapy, concurrent chemo and questionnaires</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>concurrent capecitabine or 5-FU</intervention_name>
    <description>Patients will receive 500 mg and 150 mg oral tablets of capecitabine for the prescribed dose of 825 mg/m2 BID, morning and evening (total daily dose of 1650 mg/m2 ). Dosages will be rounded to the nearest 150 mg or 500 mg. Tablets should be swallowed with water within 30 minutes after a meal. Capecitabine will be started on the Monday of the first week of brachytherapy (day 1) and taken on weekdays (Monday through Friday) during weeks of brachytherapy only.&#xD;
Administration of 5-FU should be only by the intravenous route taking care to avoid extravasation. Patients will receive 225 mg/m2/day, as a continuous venous infusion by a portable pump for the 3 weeks of treatment. The infusional 5-FU will be exchanged every 7 days.</description>
    <arm_group_label>endorectal brachytherapy, concurrent chemo and questionnaires</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Questionnaires</intervention_name>
    <description>Patients should complete the 2 quality of life questionnaires during their follow-up appointments. If they are unable to be seen in follow-up, they may complete the questionnaires at home and email or mail them back to the investigator. Should there be any incomplete or ambiguous answers, a follow-up phone call will be made by a member of the research team for clarification. Additionally, if the questionnaires have not been returned within 3 weeks after the time when they are due, a member of the research team will call the patient, and the questions will be completed over the phone.</description>
    <arm_group_label>endorectal brachytherapy, concurrent chemo and questionnaires</arm_group_label>
    <other_name>Bowel Function Assessment</other_name>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed locally residual or recurrent cancer of the&#xD;
             rectum or anus&#xD;
&#xD;
          -  Prior pelvic EBRT&#xD;
&#xD;
          -  Age &gt; or = to 18 years&#xD;
&#xD;
          -  ECOG performance status 0, 1, or 2&#xD;
&#xD;
          -  At least 4 weeks from prior major surgery or radiotherapy&#xD;
&#xD;
          -  Have undergone Surgical, Medical and Radiation Oncology evaluations to confirm :&#xD;
&#xD;
               -  Eligible for infusional 5-FU or capecitabine&#xD;
&#xD;
               -  Will not undergo surgery for the study disease&#xD;
&#xD;
               -  Able to receive HDR brachytherapy ANC ≥ 1.5 cells/mm3 and PLT ≥100,000/mm3&#xD;
&#xD;
          -  Adequate Renal function: Creatinine &lt;1.5 x the upper limit of normal (ULN) or&#xD;
             calculated creatinine clearance of ≥ 50cc/min&#xD;
&#xD;
          -  Adequate Hepatic functions: Bilirubin less than 1.5 mg/dL; (except in patients with&#xD;
             Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)&#xD;
&#xD;
          -  AST or ALT &lt;3xULN, or &lt;5x ULN if known liver metastases&#xD;
&#xD;
          -  Normal Cardiac function:&#xD;
&#xD;
               -  No active coronary artery disease;&#xD;
&#xD;
               -  No New York Heart Association class II, III or IV disease;&#xD;
&#xD;
               -  No arrhythmia requiring treatment&#xD;
&#xD;
               -  Maximum tumor length of 7 cm at time of brachytherapy treatment start&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant.&#xD;
&#xD;
          -  Women of childbearing potential who are unwilling or unable to use an acceptable&#xD;
             method to avoid pregnancy for the entire treatment period and after receipt of&#xD;
             brachytherapy. Male subjects must also agree to use effective contraception during the&#xD;
             treatment period and until 1 year after the completion of brachytherapy.&#xD;
&#xD;
          -  Patients with any other concurrent medical or psychiatric condition or disease which,&#xD;
             in the investigator's judgment, would make them inappropriate candidates for entry&#xD;
             into this study.&#xD;
&#xD;
          -  Patients on concurrent anti-cancer therapy other than that allowed in the study.&#xD;
&#xD;
          -  Contraindications to general anesthesia&#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>Abraham Wu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge (Follow Up Only)</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth (Follow Up Only)</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack (Consent and Follow up)</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester (Follow Up Only)</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Rockville Center (Follow Up Only)</name>
      <address>
        <city>Rockville Centre</city>
        <state>New York</state>
        <zip>11570</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau (Follow-Up only)</name>
      <address>
        <city>Uniondale</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 24, 2014</study_first_posted>
  <last_update_submitted>July 3, 2023</last_update_submitted>
  <last_update_submitted_qc>July 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>High-Dose-Rate Brachytherapy</keyword>
  <keyword>oral capecitabine</keyword>
  <keyword>infusional 5-FU</keyword>
  <keyword>Questionnaires</keyword>
  <keyword>14-104</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anus Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</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/NCT02199236
org study id: 14-104
nct id: NCT02199236
lead sponsor: 
The purpose of this study is to see what amount of radiation is safe to give to rectal or
      anal cancer patients who are being treated with a procedure called brachytherapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: maximum tolerated dose (MTD)
time frame: 1 year
description: will employ a standard 3+3 dose-escalation scheme. Patients will be accrued to the study in cohorts of 3. An initial cohort of 3 patients will be treated to each dose. The dose level will be escalated if none of the 3 patients exhibits any DLT within 90 days of completion of brachytherapy. Dose escalation will not take place until every patient in the prior dose cohort has been monitored for 90 days.
measure: tumor response
time frame: 3, 6, and 12 months
description: MRI with DCE & DWI (unless contraindicated) after brachytherapy
arm group label: endorectal brachytherapy, concurrent chemo and questionnaires
arm group type: Experimental
description: This is a phase I, dose-escalation study to evaluate the safety of endorectal brachytherapy with concurrent capecitabine or 5-fluoruracil (5-FU) in the management of locally recurrent/residual rectal or anal cancer in patients who have received pelvic external beam radiation therapy (EBRT) +/- chemotherapy. We will use magnetic resonance imaging (MRI) with dynamic contrast enhancement (DCE) and diffusion weighted imaging (DWI) series to contribute to the assessment of tumor response.
intervention type: Radiation
intervention name: endorectal brachytherapy
description: Patients will receive 3 fractions of endorectal brachytherapy, each spaced apart by 7 days (+/- 1 day). The three dose tiers will be 1500cGy (500cGy per fraction), 1800cGy (600cGy per fraction), and 2100cGy (700cGy per fraction).
arm group label: endorectal brachytherapy, concurrent chemo and questionnaires
intervention type: Drug
intervention name: concurrent capecitabine or 5-FU
description: Patients will receive 500 mg and 150 mg oral tablets of capecitabine for the prescribed dose of 825 mg/m2 BID, morning and evening (total daily dose of 1650 mg/m2 ). Dosages will be rounded to the nearest 150 mg or 500 mg. Tablets should be swallowed with water within 30 minutes after a meal. Capecitabine will be started on the Monday of the first week of brachytherapy (day 1) and taken on weekdays (Monday through Friday) during weeks of brachytherapy only.
Administration of 5-FU should be only by the intravenous route taking care to avoid extravasation. Patients will receive 225 mg/m2/day, as a continuous venous infusion by a portable pump for the 3 weeks of treatment. The infusional 5-FU will be exchanged every 7 days.
arm group label: endorectal brachytherapy, concurrent chemo and questionnaires
intervention type: Behavioral
intervention name: Questionnaires
description: Patients should complete the 2 quality of life questionnaires during their follow-up appointments. If they are unable to be seen in follow-up, they may complete the questionnaires at home and email or mail them back to the investigator. Should there be any incomplete or ambiguous answers, a follow-up phone call will be made by a member of the research team for clarification. Additionally, if the questionnaires have not been returned within 3 weeks after the time when they are due, a member of the research team will call the patient, and the questions will be completed over the phone.
arm group label: endorectal brachytherapy, concurrent chemo and questionnaires
other name: Bowel Function Assessment
other name: Quality of Life Assessment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Abraham Wu, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org/
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Anus Neoplasms
mesh term: Capecitabine