<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/NCT03800693</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00106610</org_study_id>
    <secondary_id>NCI-2018-02241</secondary_id>
    <secondary_id>Winship4468-18</secondary_id>
    <nct_id>NCT03800693</nct_id>
  </id_info>
  <brief_title>2 Versus 6 Hour Oxaliplatin Infusions in Patients With Gastrointestinal Cancers</brief_title>
  <official_title>Phase II Evaluation of the Effect of 2 Versus 6 Hour Oxaliplatin Infusions on Neuropathy and Pharmacokinetics in Patients With Gastrointestinal Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hematology/Oncology Pharmacy Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well giving oxaliplatin over 6 hours works in treating nerve&#xD;
      damage in patients with gastrointestinal cancers. Oxaliplatin can cause side effects such as&#xD;
      nerve damage that may delay or reduce the dose of oxaliplatin. Giving oxaliplatin over a&#xD;
      longer period of time (6 hours) may prevent or delay the development of nerve damage, which&#xD;
      may keep patients on standard doses of chemotherapy longer, without having to delay&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine the effect of 2 versus 6-hour oxaliplatin infusion time on the difference in&#xD;
      severity of sensory neuropathy as measured by patient reported outcome (PRO) scores on the&#xD;
      European Organization for Research and Treatment of Cancer (EORTC) chemotherapy-induced&#xD;
      peripheral neuropathy (CIPN-20) scale at the initiation of cycle 4.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Pharmacokinetic parameters of maximum concentration (Cmax), area under the curve (AUC),&#xD;
      time of maximum concentration (tmax), clearance, and half life (t1/2) of platinum&#xD;
      ultra-filtrate.&#xD;
&#xD;
      II. CIPN-20 sensory score changes over the duration of therapy as measured by a cumulative&#xD;
      area-under-the curve score.&#xD;
&#xD;
      III. Clinical outcomes including duration of therapy, oxaliplatin dose reductions, delays in&#xD;
      therapy, and overall dose intensity and delivery of oxaliplatin.&#xD;
&#xD;
      IV. Relationship between oxaliplatin Cmax, patient-reported acute neurotoxicity, and chronic&#xD;
      neurotoxicity by CIPN-20 scores.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 groups.&#xD;
&#xD;
      2-hour infusion group: Patients receive oxaliplatin intravenously (IV) and leucovorin IV over&#xD;
      2 hours on day 1. Patients also receive a lower dose of fluorouracil IV over 2-4 minutes&#xD;
      followed by a higher dose IV continuous over 4-6 hours on day 1. Courses repeat every 14 days&#xD;
      in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      6-hour infusion group: Patients receive oxaliplatin IV over 6 hours on day 1. Patients also&#xD;
      receive leucovorin and fluorouracil as in the 2-hour infusion group. Courses repeat every 14&#xD;
      days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 1, 3, 6, 12, and 18 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 14, 2019</start_date>
  <completion_date type="Anticipated">March 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 4, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of 2 versus 6-hour oxaliplatin infusion time on neuropathy as measured by patient reported outcome (PRO) scores on the European Organization for Research and Treatment of Cancer (EORTC) chemotherapy-induced peripheral neuropathy (CIPN-20) scale</measure>
    <time_frame>Baseline up to 60 days (course 4)</time_frame>
    <description>The EORTC-CIPN-20 sub-scales will be computed according to the standard scoring algorithm and then transformed to a 0 to 100 scale, where high scores mean less symptom burden. The primary outcome measure of difference in sensory scores of the two groups between baseline and the initiation of cycle 4 will be the driver of the analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum concentrations achieved (Cmax)</measure>
    <time_frame>At baseline and at 1, 2, 4, 6, 48, and 192 hours after initiation of oxaliplatin</time_frame>
    <description>The study will focus on maximum concentrations achieved (Cmax) with each infusion time. Data will be analyzed using non-compartmental methods via Phoenix WinNonlin analytical software, version 8.0 or higher.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in tumor size</measure>
    <time_frame>Up to 18 months after completion or discontinuation of chemotherapy</time_frame>
    <description>The study will assess changes in tumor size per standard of care assessments at screening and every 2 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of therapy</measure>
    <time_frame>Up to 18 months after completion or discontinuation of chemotherapy</time_frame>
    <description>Duration of therapy will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose density</measure>
    <time_frame>Up to 18 months after completion or discontinuation of chemotherapy</time_frame>
    <description>Dose density will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of dose holds or reductions</measure>
    <time_frame>Up to 18 months after completion or discontinuation of chemotherapy</time_frame>
    <description>Frequency of dose holds or reductions will be recorded.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Malignant Digestive System Neoplasm</condition>
  <arm_group>
    <arm_group_label>2-hour infusion group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive oxaliplatin IV and leucovorin IV over 2 hours on day 1. Patients also receive a lower dose of fluorouracil IV over 2-4 minutes followed by a higher dose IV continuous over 4-6 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>6-hour infusion group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive oxaliplatin IV over 6 hours on day 1. Patients also receive leucovorin and fluorouracil as in the 2-hour infusion group. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorouracil</intervention_name>
    <description>Given IV</description>
    <arm_group_label>2-hour infusion group</arm_group_label>
    <arm_group_label>6-hour infusion group</arm_group_label>
    <other_name>5-FU</other_name>
    <other_name>Carac</other_name>
    <other_name>Ribofluor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>2-hour infusion group</arm_group_label>
    <arm_group_label>6-hour infusion group</arm_group_label>
    <other_name>Folinic acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>2-hour infusion group</arm_group_label>
    <arm_group_label>6-hour infusion group</arm_group_label>
    <other_name>Eloxatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          -  Confirmed diagnosis of a gastrointestinal cancer&#xD;
&#xD;
          -  Plan for 4 or more cycles of FOLFOX6 (fluorouracil [with leucovorin] and oxaliplatin)&#xD;
             containing chemotherapy&#xD;
&#xD;
          -  Histologically confirmed, measurable or evaluable disease. Patients with advanced or&#xD;
             metastatic disease should have at least one measurable lesion by Response Evaluation&#xD;
             Criteria in Solid Tumors (RECIST) 1.1. Patients in the adjuvant treatment setting&#xD;
             planned to have &gt; 4 cycles of FOLFOX-containing chemotherapy are eligible and will be&#xD;
             followed per standard of care&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1,500/µL (no white blood cell growth factors allowed&#xD;
             to meet requirement)&#xD;
&#xD;
          -  Platelets ≥ 75,000/µL (may be transfused up to 72 hours prior to day 1 to meet&#xD;
             requirement)&#xD;
&#xD;
          -  Hemoglobin ≥ 8 g/dL (may be transfused up to 72 hours prior to day 1 to meet&#xD;
             requirement)&#xD;
&#xD;
          -  Creatinine clearance &gt; 30 mL/min by Cockcroft-Gault, to preserve similar dosing (85&#xD;
             mg/m²) for analysis&#xD;
&#xD;
          -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Adequate birth control when appropriate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any preexisting grade 2 or higher peripheral neuropathy&#xD;
&#xD;
          -  Patients currently receiving anticancer therapies or who have received any focal or&#xD;
             systemic anticancer therapy within 14days of the start of FOLFOX6&#xD;
&#xD;
          -  Known intolerance or hypersensitivity to any agent in FOLFOX6 or concurrent agents&#xD;
&#xD;
          -  Patients who have any known severe and/or uncontrolled medical conditions such as:&#xD;
&#xD;
               -  Unstable angina pectoris, symptomatic heart failure; (New York Heart Association&#xD;
                  class III or IV), myocardial infarction ≤ 6 months prior, serious uncontrolled&#xD;
                  cardiac arrhythmia, or any other clinically significant cardiac disease&#xD;
&#xD;
               -  Active (acute or chronic) or uncontrolled severe infection, liver disease such as&#xD;
                  cirrhosis, or decompensated liver disease&#xD;
&#xD;
          -  Patients with any history of severe hemorrhage requiring ≥ 4 units of packed red blood&#xD;
             cells (RBCs) in a 48-hour period&#xD;
&#xD;
          -  Patients with a history of non-compliance to medical regimens or who are considered&#xD;
             potentially unreliable or will not be able to complete the entire study&#xD;
&#xD;
          -  Patients who are currently part of or have participated in any clinical investigation&#xD;
             with an investigational drug within 14days prior to dosing&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP), defined as all women physiologically capable&#xD;
             of becoming pregnant, must use highly effective methods of contraception during the&#xD;
             study and 8 weeks after. Highly effective contraception methods include combination of&#xD;
             any two of the following:&#xD;
&#xD;
               -  Use of oral, injected or implanted hormonal methods of contraception or;&#xD;
&#xD;
               -  Placement of an intrauterine device (IUD) or intrauterine system (IUS);&#xD;
&#xD;
               -  Barrier methods of contraception: condom or occlusive cap (diaphragm or&#xD;
                  cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;&#xD;
&#xD;
               -  Total abstinence or;&#xD;
&#xD;
               -  Male/female sterilization Women are considered post-menopausal and not of&#xD;
                  childbearing potential if they have had 12 months of natural (spontaneous)&#xD;
                  amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of&#xD;
                  vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without&#xD;
                  hysterectomy) or tubal ligation at least six weeks prior to randomization. In the&#xD;
                  case of oophorectomy alone, only when the reproductive status of the woman has&#xD;
                  been confirmed by follow up hormone level assessment is she considered not of&#xD;
                  childbearing potential&#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>R. Donald Harvey, PharmD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>R. Donald Harvey, PharmD</last_name>
    <phone>404-778-4381</phone>
    <email>rdharve@emory.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Amber Draper, PharmD</last_name>
    <email>amber.draper@emoryhealthcare.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Emory University Hospital Midtown</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Autumn Lunceford</last_name>
      <phone>404-686-1638</phone>
      <email>patricia.autumn.lee.lunceford@emory.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital/Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Allyson Anderson</last_name>
      <phone>404-686-0239</phone>
      <email>allyson.anderson@emory.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Emory Saint Joseph's Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alicia Escobar</last_name>
      <phone>678-843-7029</phone>
      <email>alicia.m.escobar@emory.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>December 12, 2022</last_update_submitted>
  <last_update_submitted_qc>December 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>R. Donald Harvey</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastrointestinal Neoplasms</mesh_term>
    <mesh_term>Digestive System Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03800693
org study id: IRB00106610
secondary id: NCI-2018-02241
secondary id: Winship4468-18
nct id: NCT03800693
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well giving oxaliplatin over 6 hours works in treating nerve
      damage in patients with gastrointestinal cancers. Oxaliplatin can cause side effects such as
      nerve damage that may delay or reduce the dose of oxaliplatin. Giving oxaliplatin over a
      longer period of time (6 hours) may prevent or delay the development of nerve damage, which
      may keep patients on standard doses of chemotherapy longer, without having to delay
      treatment.
PRIMARY OBJECTIVE:

      I. To determine the effect of 2 versus 6-hour oxaliplatin infusion time on the difference in
      severity of sensory neuropathy as measured by patient reported outcome (PRO) scores on the
      European Organization for Research and Treatment of Cancer (EORTC) chemotherapy-induced
      peripheral neuropathy (CIPN-20) scale at the initiation of cycle 4.

      SECONDARY OBJECTIVES:

      I. Pharmacokinetic parameters of maximum concentration (Cmax), area under the curve (AUC),
      time of maximum concentration (tmax), clearance, and half life (t1/2) of platinum
      ultra-filtrate.

      II. CIPN-20 sensory score changes over the duration of therapy as measured by a cumulative
      area-under-the curve score.

      III. Clinical outcomes including duration of therapy, oxaliplatin dose reductions, delays in
      therapy, and overall dose intensity and delivery of oxaliplatin.

      IV. Relationship between oxaliplatin Cmax, patient-reported acute neurotoxicity, and chronic
      neurotoxicity by CIPN-20 scores.

      OUTLINE: Patients are randomized to 1 of 2 groups.

      2-hour infusion group: Patients receive oxaliplatin intravenously (IV) and leucovorin IV over
      2 hours on day 1. Patients also receive a lower dose of fluorouracil IV over 2-4 minutes
      followed by a higher dose IV continuous over 4-6 hours on day 1. Courses repeat every 14 days
      in the absence of disease progression or unacceptable toxicity.

      6-hour infusion group: Patients receive oxaliplatin IV over 6 hours on day 1. Patients also
      receive leucovorin and fluorouracil as in the 2-hour infusion group. Courses repeat every 14
      days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 1, 3, 6, 12, and 18 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Effect of 2 versus 6-hour oxaliplatin infusion time on neuropathy as measured by patient reported outcome (PRO) scores on the European Organization for Research and Treatment of Cancer (EORTC) chemotherapy-induced peripheral neuropathy (CIPN-20) scale
time frame: Baseline up to 60 days (course 4)
description: The EORTC-CIPN-20 sub-scales will be computed according to the standard scoring algorithm and then transformed to a 0 to 100 scale, where high scores mean less symptom burden. The primary outcome measure of difference in sensory scores of the two groups between baseline and the initiation of cycle 4 will be the driver of the analysis.
measure: Maximum concentrations achieved (Cmax)
time frame: At baseline and at 1, 2, 4, 6, 48, and 192 hours after initiation of oxaliplatin
description: The study will focus on maximum concentrations achieved (Cmax) with each infusion time. Data will be analyzed using non-compartmental methods via Phoenix WinNonlin analytical software, version 8.0 or higher.
measure: Changes in tumor size
time frame: Up to 18 months after completion or discontinuation of chemotherapy
description: The study will assess changes in tumor size per standard of care assessments at screening and every 2 months.
measure: Duration of therapy
time frame: Up to 18 months after completion or discontinuation of chemotherapy
description: Duration of therapy will be recorded.
measure: Dose density
time frame: Up to 18 months after completion or discontinuation of chemotherapy
description: Dose density will be recorded.
measure: Frequency of dose holds or reductions
time frame: Up to 18 months after completion or discontinuation of chemotherapy
description: Frequency of dose holds or reductions will be recorded.
arm group label: 2-hour infusion group
arm group type: Active Comparator
description: Patients receive oxaliplatin IV and leucovorin IV over 2 hours on day 1. Patients also receive a lower dose of fluorouracil IV over 2-4 minutes followed by a higher dose IV continuous over 4-6 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
arm group label: 6-hour infusion group
arm group type: Experimental
description: Patients receive oxaliplatin IV over 6 hours on day 1. Patients also receive leucovorin and fluorouracil as in the 2-hour infusion group. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Fluorouracil
description: Given IV
arm group label: 2-hour infusion group
arm group label: 6-hour infusion group
other name: 5-FU
other name: Carac
other name: Ribofluor
intervention type: Drug
intervention name: Leucovorin
description: Given IV
arm group label: 2-hour infusion group
arm group label: 6-hour infusion group
other name: Folinic acid
intervention type: Drug
intervention name: Oxaliplatin
description: Given IV
arm group label: 2-hour infusion group
arm group label: 6-hour infusion group
other name: Eloxatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: R. Donald Harvey, PharmD
role: Principal Investigator
affiliation: Emory University
last name: R. Donald Harvey, PharmD
phone: 404-778-4381
email: rdharve@emory.edu
last name: Amber Draper, PharmD
email: amber.draper@emoryhealthcare.org
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: R. Donald Harvey
investigator title: Principal Investigator
mesh term: Gastrointestinal Neoplasms
mesh term: Digestive System Neoplasms
mesh term: Leucovorin
mesh term: Fluorouracil
mesh term: Oxaliplatin
sharing ipd: No