<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/NCT03781323</url>
  </required_header>
  <id_info>
    <org_study_id>UGIC18095</org_study_id>
    <nct_id>NCT03781323</nct_id>
  </id_info>
  <brief_title>Neoadjuvant FOLFOX Therapy With Short Course Radiation and Active Surveillance in Locally Advanced Rectal Cancer</brief_title>
  <official_title>Neoadjuvant FOLFOX Therapy With Short Course Radiation and Active Surveillance in Locally Advanced Rectal Cancer: A Phase II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Rochester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Rochester</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the treatment of patients with locally advanced&#xD;
      rectal cancer for complete response to neoadjuvant chemotherapy without the use of radiation&#xD;
      and surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      These patients will be evaluated for complete clinical response (cCR) after completing 10&#xD;
      cycles of FOLFOX (fluorouracil, leucovorin, oxaliplatin) chemotherapy, with interval analysis&#xD;
      after six cycles. Patients who have stable or progressive disease will be treated per&#xD;
      discretion of the treating physician following multidisciplinary discussion. Those determined&#xD;
      to have partial or complete response will complete full neoadjuvant treatment and undergo&#xD;
      close surveillance with watchful waiting for local recurrence without immediate surgery. The&#xD;
      primary endpoint of this study will be the rate of cCR, which is to include complete and near&#xD;
      complete clinical response, with secondary endpoints of disease free survival (DFS), overall&#xD;
      survival (OS), quality of life (QOL), as well as evaluation of safety and toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 3, 2019</start_date>
  <completion_date type="Anticipated">June 1, 2027</completion_date>
  <primary_completion_date type="Actual">June 1, 2022</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>Proportion of Patients With a Complete Clinical Response.</measure>
    <time_frame>1 year</time_frame>
    <description>A complete response will consist of a digital rectal exam with normal appearing mucosa and sigmoidoscopy/proctoscopy with scarring but no nodularity or ulcerations.&#xD;
A near complete response will consist of digital rectal exam with smooth or minor mucosal abnormalities, and sigmoidoscopy/proctoscopy with small mucosal abnormalities, or superficial ulceration or erythematous scarring.&#xD;
Partial response, in our study, will be those tumors read with RECIST version 1.1 criteria with a ≥20% decrease in size without obtaining near or complete response.&#xD;
Stable disease, in our study, will be those tumors read with RECIST criteria with a &lt;20% decrease in size without obtaining near or complete response.&#xD;
Progressive disease will be those tumors with &gt;20% increase in size by RECIST version 1.1 criteria on imaging.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of Patients With Survival</measure>
    <time_frame>5 years</time_frame>
    <description>Will be measured by physical exams</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Patients With Survival</measure>
    <time_frame>5 years</time_frame>
    <description>Will be measured by laboratory testing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Patients With Survival</measure>
    <time_frame>5 years</time_frame>
    <description>Will be measured by proctoscopy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Patients With Survival</measure>
    <time_frame>5 years</time_frame>
    <description>Will be measured by sigmoidoscopy</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Advanced Rectal Cancer</condition>
  <arm_group>
    <arm_group_label>mFOLFOX (5-Fluorouracil Leucovorin Oxaliplatin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.&#xD;
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFOX</intervention_name>
    <description>Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.&#xD;
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.</description>
    <arm_group_label>mFOLFOX (5-Fluorouracil Leucovorin Oxaliplatin)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participants must be &gt;18 years old at time of diagnosis&#xD;
&#xD;
          2. Histologically confirmed adenocarcinoma of the rectum from biopsy, defined as&#xD;
             adenocarcinoma &lt;15 cm from the anal verge&#xD;
&#xD;
          3. Clinical staging including T3N0 tumors, or T1-3 with N1-2a disease&#xD;
&#xD;
          4. Patients with lower rectal cancer deemed by surgery to not be candidates for sphincter&#xD;
             sparing surgery are eligible to participate&#xD;
&#xD;
          5. There must be no evidence of metastatic disease any time prior to initiation of study&#xD;
&#xD;
          6. Rectal tumors must be determined as likely requiring total mesorectal excision (TME)&#xD;
&#xD;
          7. Participant must be treatment naïve for rectal cancer, with no prior radiation&#xD;
             chemotherapy, radiation, or surgery for specific rectal cancer&#xD;
&#xD;
          8. No history of prior pelvic radiation&#xD;
&#xD;
          9. No prior administration of platinum agents&#xD;
&#xD;
         10. No active infections requiring intravenous antibiotics&#xD;
&#xD;
         11. No additional active malignancy&#xD;
&#xD;
         12. No prior treatment of any malignancy within the past 3 years&#xD;
&#xD;
         13. Baseline lab work must meet the following parameters:&#xD;
&#xD;
               1. Absolute neutrophil count (ANC)&gt;1500/mm3&#xD;
&#xD;
               2. Platelet count&gt;100,000/mm3&#xD;
&#xD;
               3. Hemoglobin&gt;8.0 g/dL&#xD;
&#xD;
               4. Total bilirubin and creatinine &lt; 1.5x upper limit of normal (ULN)&#xD;
&#xD;
               5. AST and ALT &lt; 3x ULN&#xD;
&#xD;
         14. Women of childbearing potential (WCBP) will be defined as those biologically capable&#xD;
             of becoming pregnant. WCBP must be negative for pregnancy testing (urine or blood) and&#xD;
             agree to use effective contraception. Viable contraception should be used after trial&#xD;
             screening, before initiation of chemotherapy, and throughout the duration of active&#xD;
             treatment in the study.&#xD;
&#xD;
         15. Participants must be read and explained the purposes of the study, and sign a&#xD;
             statement of informed consent prior to participation. Those who do not read or&#xD;
             understand English are eligible and may be consented according to institutional&#xD;
             federal regulations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Recurrent or refractory rectal adenocarcinoma&#xD;
&#xD;
          2. T1N0, T2N0, T4a, T4b, or N2b tumors&#xD;
&#xD;
          3. Any evidence of metastatic disease&#xD;
&#xD;
          4. Primary unresectable rectal cancer. A tumor will be considered unresectable when&#xD;
             invading adjacent organs such that an en bloc resection cannot achieve negative&#xD;
             margins&#xD;
&#xD;
          5. Patients with threatened margins, defined as tumor &lt;1 mm from circumferential&#xD;
             resection margins or mesorectal fascia&#xD;
&#xD;
          6. Patients unable to undergo MRI imaging&#xD;
&#xD;
          7. Patient with a history of any arterial thrombotic event within the past 6 months. This&#xD;
             includes angina, myocardial infarction, transient ischemic attack, or cerebral&#xD;
             vascular accident.&#xD;
&#xD;
          8. Patients with history of venous thrombotic episodes such as deep vein thrombosis,&#xD;
             pulmonary embolus occurring more than 6 months prior to enrollment may be considered&#xD;
             for protocol participation, provided they are on stable doses of anticoagulant&#xD;
             therapy. Patients who are anticoagulated for atrial fibrillation or other conditions&#xD;
             may participate only if on stable doses of anticoagulant therapy.&#xD;
&#xD;
          9. Patients with cardiovascular, hepatic, or renal systemic diseases that would preclude&#xD;
             use of chemotherapy&#xD;
&#xD;
         10. Peripheral neuropathy&gt;grade 1 by Common Terminology Criteria for Adverse Events, or&#xD;
             CTCAEa&#xD;
&#xD;
         11. The patient must not be on any clinical trials involving other experimental therapies&#xD;
             before or during study treatment&#xD;
&#xD;
         12. Women who are currently pregnant or breast-feeding&#xD;
&#xD;
         13. Men and women expecting to father/conceive children&#xD;
&#xD;
         14. Patients with any other concord medical or psychiatric condition which were deemed&#xD;
             inappropriate for entry into the study per the investigator.&#xD;
&#xD;
         15. History of other invasive malignancy within the past 3 years, except for adequately&#xD;
             treated non-melanoma skin cancer, ductal carcinoma in situ, bladder carcinoma in situ&#xD;
             or carcinoma in situ of the cervix.&#xD;
&#xD;
        aCTCAE version 5.0 from Department of Health and Human Services&#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>Richard Dunne</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Rochester</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Rochester, James P. Wilmot Cancer Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 13, 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>
  <results_first_submitted>August 16, 2023</results_first_submitted>
  <results_first_submitted_qc>August 16, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">September 11, 2023</results_first_posted>
  <last_update_submitted>August 16, 2023</last_update_submitted>
  <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Rochester</investigator_affiliation>
    <investigator_full_name>Richard Dunne</investigator_full_name>
    <investigator_title>Associate Professor of Hematology/Oncology</investigator_title>
  </responsible_party>
  <keyword>Advanced rectal cancer</keyword>
  <keyword>FOLFOX (fluorouracil, leucovorin, oxaliplatin)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 9, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03781323/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 4, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03781323/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>13 patients were consented, 1 failed screening</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>mFOLFOX (5-Fluorouracil Leucovorin Oxaliplatin)</title>
          <description>Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.&#xD;
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.&#xD;
FOLFOX: Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.&#xD;
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>mFOLFOX (5-Fluorouracil Leucovorin Oxaliplatin)</title>
          <description>Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.&#xD;
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.&#xD;
FOLFOX: Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.&#xD;
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51.4" lower_limit="33" upper_limit="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Patients With a Complete Clinical Response.</title>
        <description>A complete response will consist of a digital rectal exam with normal appearing mucosa and sigmoidoscopy/proctoscopy with scarring but no nodularity or ulcerations.&#xD;
A near complete response will consist of digital rectal exam with smooth or minor mucosal abnormalities, and sigmoidoscopy/proctoscopy with small mucosal abnormalities, or superficial ulceration or erythematous scarring.&#xD;
Partial response, in our study, will be those tumors read with RECIST version 1.1 criteria with a ≥20% decrease in size without obtaining near or complete response.&#xD;
Stable disease, in our study, will be those tumors read with RECIST criteria with a &lt;20% decrease in size without obtaining near or complete response.&#xD;
Progressive disease will be those tumors with &gt;20% increase in size by RECIST version 1.1 criteria on imaging.</description>
        <time_frame>1 year</time_frame>
        <population>Data was missing for one participant.</population>
        <group_list>
          <group group_id="O1">
            <title>mFOLFOX (5-Fluorouracil Leucovorin Oxaliplatin)</title>
            <description>Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.&#xD;
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.&#xD;
FOLFOX: Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.&#xD;
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Patients With a Complete Clinical Response.</title>
          <description>A complete response will consist of a digital rectal exam with normal appearing mucosa and sigmoidoscopy/proctoscopy with scarring but no nodularity or ulcerations.&#xD;
A near complete response will consist of digital rectal exam with smooth or minor mucosal abnormalities, and sigmoidoscopy/proctoscopy with small mucosal abnormalities, or superficial ulceration or erythematous scarring.&#xD;
Partial response, in our study, will be those tumors read with RECIST version 1.1 criteria with a ≥20% decrease in size without obtaining near or complete response.&#xD;
Stable disease, in our study, will be those tumors read with RECIST criteria with a &lt;20% decrease in size without obtaining near or complete response.&#xD;
Progressive disease will be those tumors with &gt;20% increase in size by RECIST version 1.1 criteria on imaging.</description>
          <population>Data was missing for one participant.</population>
          <units>proportion or participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Patients With Survival</title>
        <description>Will be measured by physical exams</description>
        <time_frame>5 years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Patients With Survival</title>
        <description>Will be measured by laboratory testing</description>
        <time_frame>5 years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Patients With Survival</title>
        <description>Will be measured by proctoscopy</description>
        <time_frame>5 years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Patients With Survival</title>
        <description>Will be measured by sigmoidoscopy</description>
        <time_frame>5 years</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>mFOLFOX (5-Fluorouracil Leucovorin Oxaliplatin)</title>
          <description>Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.&#xD;
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.&#xD;
FOLFOX: Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.&#xD;
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>colonic performation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>ileal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>anemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Mediport Thrombus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hematochezia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Heartburn</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal Cramping</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypoactive Bowel Sounds</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Mouth sores</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Cold Sensitivity in hand and throat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypothermia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Mediport Incision Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Lip infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Lesion from tick bite on upper back</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Wound complication</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>alanine aminotransferase increase</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>anorexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neck/Jawline pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>anxiety</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Cold Sensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sleep Disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep Disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal spotting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nasal Sores</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Irritant dermatitis around stoma</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diaphoretic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Erythema to fingertips</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Richard Dunne</name_or_title>
      <organization>University of Rochester</organization>
      <phone>585-275-5823</phone>
      <email>Richard_Dunne@urmc.rochester.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03781323
org study id: UGIC18095
nct id: NCT03781323
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to evaluate the treatment of patients with locally advanced
      rectal cancer for complete response to neoadjuvant chemotherapy without the use of radiation
      and surgery.
These patients will be evaluated for complete clinical response (cCR) after completing 10
      cycles of FOLFOX (fluorouracil, leucovorin, oxaliplatin) chemotherapy, with interval analysis
      after six cycles. Patients who have stable or progressive disease will be treated per
      discretion of the treating physician following multidisciplinary discussion. Those determined
      to have partial or complete response will complete full neoadjuvant treatment and undergo
      close surveillance with watchful waiting for local recurrence without immediate surgery. The
      primary endpoint of this study will be the rate of cCR, which is to include complete and near
      complete clinical response, with secondary endpoints of disease free survival (DFS), overall
      survival (OS), quality of life (QOL), as well as evaluation of safety and toxicity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of Patients With a Complete Clinical Response.
time frame: 1 year
description: A complete response will consist of a digital rectal exam with normal appearing mucosa and sigmoidoscopy/proctoscopy with scarring but no nodularity or ulcerations.
A near complete response will consist of digital rectal exam with smooth or minor mucosal abnormalities, and sigmoidoscopy/proctoscopy with small mucosal abnormalities, or superficial ulceration or erythematous scarring.
Partial response, in our study, will be those tumors read with RECIST version 1.1 criteria with a ≥20% decrease in size without obtaining near or complete response.
Stable disease, in our study, will be those tumors read with RECIST criteria with a <20% decrease in size without obtaining near or complete response.
Progressive disease will be those tumors with >20% increase in size by RECIST version 1.1 criteria on imaging.
measure: Proportion of Patients With Survival
time frame: 5 years
description: Will be measured by physical exams
measure: Proportion of Patients With Survival
time frame: 5 years
description: Will be measured by laboratory testing
measure: Proportion of Patients With Survival
time frame: 5 years
description: Will be measured by proctoscopy
measure: Proportion of Patients With Survival
time frame: 5 years
description: Will be measured by sigmoidoscopy
arm group label: mFOLFOX (5-Fluorouracil Leucovorin Oxaliplatin)
arm group type: Experimental
description: Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.
intervention type: Drug
intervention name: FOLFOX
description: Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.
arm group label: mFOLFOX (5-Fluorouracil Leucovorin Oxaliplatin)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Richard Dunne
role: Principal Investigator
affiliation: University of Rochester
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Rochester
investigator full name: Richard Dunne
investigator title: Associate Professor of Hematology/Oncology
mesh term: Rectal Neoplasms
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 