<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/NCT04417699</url>
  </required_header>
  <id_info>
    <org_study_id>2021000326</org_study_id>
    <nct_id>NCT04417699</nct_id>
  </id_info>
  <brief_title>SHOrt Course Radiation and TASOX (TAS102 Plus Oxaliplatin) Chemotherapy in Operable Rectal Cancer</brief_title>
  <acronym>SHORT</acronym>
  <official_title>SHORT: SHOrt Course Radiation and TASOX (TAS102 Plus Oxaliplatin) Chemotherapy in Operable Rectal Cancer, a Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Providence Health &amp; Services</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Taiho Oncology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Providence Health &amp; Services</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      TASOX can be safely and efficaciously delivered after short course radiation, resulting in&#xD;
      significant pathologic downstaging, allowing for an R0 pelvic resection, and providing local&#xD;
      control in appropriately selected stage II/III rectal cancer patients treated with&#xD;
      contemporary TME-based surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this phase II study patients will be treated with short-course preoperative irradiation&#xD;
      (25 Gy in five fractions of 5 Gy) followed by 6 (six) 2-week cycles of TASOX followed by&#xD;
      total mesorectal excision (TME) for patients with resectable rectal cancer (clinical T3c/dN0,&#xD;
      T3c/dN1, T2N1). Eligible study subjects include adults who are candidates for curative intent&#xD;
      sphincter-sparing surgery and lack high risk features such as tumor encroaching upon the&#xD;
      mesorectal-fascia or low tumors who need an Abdominal-Perineal Resection (APR).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 5, 2022</start_date>
  <completion_date type="Anticipated">April 2025</completion_date>
  <primary_completion_date type="Anticipated">October 2024</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>Achieve a reduction by at least 5.8 in Neoadjuvant Response (NAR) score compared to historic controls with NAR of 14.59</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>determine whether pre-operative short-course radiation therapy (SRT) and 6 cycles of TASOX offers condensed radiation and total neoadjuvant therapy for intermediate risk rectal cancer.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>The secondary objective is to describe Incidence of Treatment-Emergent Adverse Events and surgery complications among treated subjects.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">27</enrollment>
  <condition>Rectal Cancer</condition>
  <arm_group>
    <arm_group_label>TAS102 plus Oxaliplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oxaliplatin 85mg/m2 IV over 2 hours and TAS-102 (35 mg/m2/dose) orally BID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAS 102</intervention_name>
    <description>Oral medication over Days 1-5</description>
    <arm_group_label>TAS102 plus Oxaliplatin</arm_group_label>
    <other_name>Tipiracil hydrochloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Administered by intravenous infusion over 2 hours on day 1</description>
    <arm_group_label>TAS102 plus Oxaliplatin</arm_group_label>
    <other_name>Eloxatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age of at least 18 years.&#xD;
&#xD;
          2. Newly diagnosis of rectal adenocarcinoma.&#xD;
&#xD;
          3. ECOG Performance Status (PS): 0, 1 or 2.&#xD;
&#xD;
          4. Candidate for sphincter-sparing surgical resection prior to initiation of neoadjuvant&#xD;
             therapy according to the primary surgeon.&#xD;
&#xD;
          5. Clinical Stage: T1/N1, T2/N1, T3/N1, T3c/dN0.&#xD;
&#xD;
          6. Absence of metastatic disease. Clinical staging is based on physical exam by the&#xD;
             primary surgeon, CT scan of the chest/abdomen, and pelvic MRI.&#xD;
&#xD;
             Node positivity determination: Entry criteria nodes will be measured in short-axis&#xD;
             diameter and for the purposes of study entry will be considered positive if 8 mm or&#xD;
             greater in short axis.&#xD;
&#xD;
             Radiographic N2 status is estimated as: 4 or more nodes that measure 8mm or more in&#xD;
             short-axis.&#xD;
&#xD;
             Radiographic N1 status is estimated as: fewer than 4 lymph nodes that measure 8 mm or&#xD;
             greater in short axis but 1 or more lymph nodes that measure 8 mm or greater.&#xD;
&#xD;
             Nodal Metastatic Disease: nodal stations considered suspicious for metastatic disease&#xD;
             (M1) for rectal cancer are common iliac, external iliac and inguinal nodes.&#xD;
&#xD;
          7. No evidence of tumor that is adherent to the mesorectal fascia and the ability to&#xD;
             perform a curative intent sphincter-sparing TME resection at diagnosis. See exclusion&#xD;
             criterion 4&#xD;
&#xD;
          8. The following laboratory values obtained ≤ 28 days prior to registration.&#xD;
&#xD;
               -  Platelet count ≥ 100,000/mm^3&#xD;
&#xD;
               -  Hemoglobin &gt; 8.0 g/dL&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
               -  SGOT (AST) ≤ 3 x ULN&#xD;
&#xD;
               -  SGPT (ALT) ≤ 3 x ULN&#xD;
&#xD;
               -  Creatinine ≤1.5 x ULN&#xD;
&#xD;
          9. Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing&#xD;
             potential only.&#xD;
&#xD;
         10. A patient of child-bearing potential is willing to employ adequate contraception. It&#xD;
             includes any of the followings: abstinence, oral contraceptives, implantable hormonal&#xD;
             contraceptives, or double barrier method (diaphragm plus condom). See exclusion&#xD;
             criterion 8&#xD;
&#xD;
         11. Provide informed written consent.&#xD;
&#xD;
         12. Willing to return to enrolling medical site for all study assessments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Clinical T4 tumors.&#xD;
&#xD;
          2. Clinical N2 disease estimated as four or more lymph nodes that are ≥8 mm.&#xD;
&#xD;
          3. Primary surgeon indicates need for abdominoperineal (APR) at baseline.&#xD;
&#xD;
          4. Evidence that the tumor is adherent to or invading the mesorectal fascia on imaging&#xD;
             studies such that the surgeon would not be able to perform an R0 resection (one with&#xD;
             negative margins).&#xD;
&#xD;
             Distance of the Tumor from the Mesorectal Fascia:&#xD;
&#xD;
             Patients with tumors with a distance of 1mm or less from the mesorectal fascia&#xD;
             reflection have threatened radial margins and are ineligible.&#xD;
&#xD;
          5. Tumor is causing symptomatic bowel obstruction or patients who have had a temporary&#xD;
             diverting ostomy are ineligible.&#xD;
&#xD;
          6. Chemotherapy within 5 years prior to registration. (Hormonal therapy is allowable if&#xD;
             the disease free interval is ≥ 5 years.)&#xD;
&#xD;
          7. Any prior pelvic radiation.&#xD;
&#xD;
          8. Any of the following because this study involves an agent that has known genotoxic,&#xD;
             mutagenic and teratogenic effects:&#xD;
&#xD;
               -  Pregnant women&#xD;
&#xD;
               -  Nursing women&#xD;
&#xD;
               -  Men or women of childbearing potential who are unwilling to employ adequate&#xD;
                  contraception&#xD;
&#xD;
          9. Co-morbid illnesses or other concurrent disease which, in the judgment of the treating&#xD;
             investigator obtaining informed consent, would make the patient inappropriate for&#xD;
             entry into this study or interfere significantly with the proper assessment of safety&#xD;
             and toxicity of the prescribed regimens.&#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>Hagen Kennecke, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Providence Health &amp; Services</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mary McCormick, RN</last_name>
    <phone>5032159570</phone>
    <email>mary.mccormick@providence.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of California, Irvine</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jason A. Zell, DO, MPH, MS</last_name>
      <phone>714-456-5153</phone>
      <email>jzell@uci.edu</email>
    </contact>
    <investigator>
      <last_name>Jason A. Zell, DO, MPH, MS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Columbia University Irving Medical Center/NYPH</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lisa A. Kachnic, MD</last_name>
    </contact>
    <investigator>
      <last_name>Lisa A. Kachnic, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mary McCormick, RN</last_name>
      <phone>503-215-9570</phone>
      <email>mary.mccormick@providence.org</email>
    </contact>
    <investigator>
      <last_name>Hagen Kennecke, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Virginia Mason Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98101</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Huong Pham, MD</last_name>
      <phone>206-223-6801</phone>
      <email>Huong.Pham@virginiamason.org</email>
    </contact>
    <investigator>
      <last_name>Huong Pham, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>December 13, 2022</last_update_submitted>
  <last_update_submitted_qc>December 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SHORT</keyword>
  <keyword>short course radiation,</keyword>
  <keyword>TASOX</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxaliplatin</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/NCT04417699
org study id: 2021000326
nct id: NCT04417699
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
TASOX can be safely and efficaciously delivered after short course radiation, resulting in
      significant pathologic downstaging, allowing for an R0 pelvic resection, and providing local
      control in appropriately selected stage II/III rectal cancer patients treated with
      contemporary TME-based surgery.
In this phase II study patients will be treated with short-course preoperative irradiation
      (25 Gy in five fractions of 5 Gy) followed by 6 (six) 2-week cycles of TASOX followed by
      total mesorectal excision (TME) for patients with resectable rectal cancer (clinical T3c/dN0,
      T3c/dN1, T2N1). Eligible study subjects include adults who are candidates for curative intent
      sphincter-sparing surgery and lack high risk features such as tumor encroaching upon the
      mesorectal-fascia or low tumors who need an Abdominal-Perineal Resection (APR).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Achieve a reduction by at least 5.8 in Neoadjuvant Response (NAR) score compared to historic controls with NAR of 14.59
time frame: Through study completion, an average of 6 months
description: determine whether pre-operative short-course radiation therapy (SRT) and 6 cycles of TASOX offers condensed radiation and total neoadjuvant therapy for intermediate risk rectal cancer.
measure: Safety and Tolerability
time frame: Through study completion, an average of 6 months
description: The secondary objective is to describe Incidence of Treatment-Emergent Adverse Events and surgery complications among treated subjects.
arm group label: TAS102 plus Oxaliplatin
arm group type: Experimental
description: Oxaliplatin 85mg/m2 IV over 2 hours and TAS-102 (35 mg/m2/dose) orally BID
intervention type: Drug
intervention name: TAS 102
description: Oral medication over Days 1-5
arm group label: TAS102 plus Oxaliplatin
other name: Tipiracil hydrochloride
intervention type: Drug
intervention name: Oxaliplatin
description: Administered by intravenous infusion over 2 hours on day 1
arm group label: TAS102 plus Oxaliplatin
other name: Eloxatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hagen Kennecke, MD
role: Principal Investigator
affiliation: Providence Health & Services
last name: Mary McCormick, RN
phone: 5032159570
email: mary.mccormick@providence.org
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Rectal Neoplasms
mesh term: Oxaliplatin