<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/NCT04505553</url>
  </required_header>
  <id_info>
    <org_study_id>RG1121095</org_study_id>
    <secondary_id>NCI-2020-05455</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <secondary_id>10559</secondary_id>
    <nct_id>NCT04505553</nct_id>
  </id_info>
  <brief_title>Oral Cryotherapy Plus Acupressure and Acupuncture Versus Oral Cryotherapy for Decreasing Chemotherapy-Induced Peripheral Neuropathy From Oxaliplatin-Based Chemotherapy in Patients With Gastrointestinal Cancer</brief_title>
  <official_title>Pilot Study of Oral Cryotherapy vs. Oral Cryotherapy Plus Acupuncture and Acupressure to Decrease Chemotherapy-Induced Peripheral Neuropathy From Oxaliplatin-Based Chemotherapy for GI Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Safeway Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial investigates how well oral cryotherapy plus acupressure and acupuncture&#xD;
      compared with oral cryotherapy alone work in decreasing chemotherapy-induced peripheral&#xD;
      neuropathy in patients with gastrointestinal cancer who are receiving oxaliplatin-based&#xD;
      chemotherapy. Acupressure is the application of pressure or localized massage to specific&#xD;
      sites on the body to control symptoms such as pain or nausea. Acupuncture is the technique of&#xD;
      inserting thin needles through the skin at specific points on the body to control pain and&#xD;
      other symptoms. Cryotherapy uses cold temperature such as oral ice chips to prevent&#xD;
      abnormally increased pain sensation. Giving oral cryotherapy with acupressure and acupuncture&#xD;
      may work better in decreasing chemotherapy-induced peripheral neuropathy from&#xD;
      oxaliplatin-based chemotherapy in patients with gastrointestinal cancer compared to oral&#xD;
      cryotherapy alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Patients undergo acupuncture during chemotherapy infusion on day 1 and fluorouracil&#xD;
      pump disconnect on day 3 of each biweekly chemotherapy infusion over 12 weeks. Patients also&#xD;
      undergo self-administered acupressure over 11 minutes daily for 12 weeks and undergo standard&#xD;
      of care oral cryotherapy.&#xD;
&#xD;
      ARM II: Patients undergo standard of care oral cryotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2021</start_date>
  <completion_date type="Anticipated">August 25, 2024</completion_date>
  <primary_completion_date type="Anticipated">February 25, 2024</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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Severity of chemotherapy-induced peripheral neuropathy (CIPN)</measure>
    <time_frame>At 3 months</time_frame>
    <description>Measured by the European Organization for Research and Treatment of Cancer (EORTC)-CIPN 20. Severity of CIPN will be summarized for each treatment arm, and treatment comparisons made via linear regression model with adjustment for baseline severity level. The EORTC QLQ-CIPN20 is a 20-item questionnaire that evaluates CIPN using 3 subscales that assess sensory (9 items), motor (8 items), and autonomic (3 items) symptoms and functioning with each item measured on a 1-4 scale (1, not at all; 4, very much). The sensory subscale raw scores range from 1 to 36. The CIPN-20 subscale raw scores are linearly converted to a 0-100 scale such that a high score corresponds to a worse condition or more symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of grade 2 or higher CIPN</measure>
    <time_frame>3 months</time_frame>
    <description>Measured by Common Terminology Criteria for Adverse Events (CTCAE) version 5. Incidences of CIPN (grade 2 or higher), pain, fatigue, nausea, and anxiety will be compared between treatment arms using Chi-squared or Fisher's exact tests as appropriate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of CIPN: Neuropen assessment of patients' perceived pain and pressure</measure>
    <time_frame>3 months</time_frame>
    <description>The Neuropen is used to assess touch and pressure perception as well as protective pain and sharpness sensation. Touch and pressure sensation will be assessed using a 10-g monofilament on the subject's dominant foot. Pain and subjective sharpness sensation will be assessed using the 40-g Neurotip on the dominant foot. Loss of pain and pressure sensation are associated with increased CIPN.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of CIPN: Tuning fork vibration sensation testing</measure>
    <time_frame>3 months</time_frame>
    <description>A study-specific 128-Hz tuning fork will be used to assess vibration sensation on dominant lower extremity and dominant upper extremity sites. If the patient feels the vibration for 15 seconds or longer, this is defined as normal. If the patient feels the vibration less than 15 seconds, this is defined as absent or decreased vibration sensation. Vibration sensation is lost sooner in CIPN, which means that shorter duration of vibration scores are associated with increased CIPN.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients assigned to the intervention arm who complete 60% of acupuncture treatments</measure>
    <time_frame>3 months</time_frame>
    <description>Adherence to acupuncture treatment among patients in the intervention arm will be described as a proportion with 95% confidence interval. Reasons for treatment non-adherence and delivered dose intensity of chemotherapy will be noted.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of pain, fatigue, nausea, and anxiety</measure>
    <time_frame>3 months</time_frame>
    <description>Measured by patient-reported (National Cancer Institute [NCI] Patient Reported Outcomes [PRO]-CTCAE, Brief Pain Inventory [BPI], oral dysesthesia) and provider-assessed (CTCAE version 5) grading scales.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">56</enrollment>
  <condition>Appendix Carcinoma</condition>
  <condition>Colon Carcinoma</condition>
  <condition>Esophageal Carcinoma</condition>
  <condition>Gastric Carcinoma</condition>
  <condition>Liver and Intrahepatic Bile Duct Carcinoma</condition>
  <condition>Malignant Digestive System Neoplasm</condition>
  <condition>Pancreatic Carcinoma</condition>
  <condition>Rectal Carcinoma</condition>
  <condition>Small Intestinal Carcinoma</condition>
  <condition>Anal Carcinoma</condition>
  <condition>Digestive System Carcinoma</condition>
  <condition>Digestive System Neuroendocrine Tumor</condition>
  <condition>Pancreatic Neuroendocrine Tumor</condition>
  <arm_group>
    <arm_group_label>Arm I (acupuncture, acupressure, cryotherapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo acupuncture during chemotherapy infusion on day 1 and fluorouracil pump disconnect on day 3 of each biweekly chemotherapy infusion over 12 weeks. Patients also undergo self-administered acupressure over 11 minutes daily for 12 weeks and undergo standard of care oral cryotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (cryotherapy)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients undergo standard of care oral cryotherapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Acupuncture Therapy</intervention_name>
    <description>Undergo acupuncture</description>
    <arm_group_label>Arm I (acupuncture, acupressure, cryotherapy)</arm_group_label>
    <other_name>Acupuncture</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Acupressure Therapy</intervention_name>
    <description>Undergo acupressure</description>
    <arm_group_label>Arm I (acupuncture, acupressure, cryotherapy)</arm_group_label>
    <other_name>acupressure</other_name>
    <other_name>Ischemic Compression</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Oral Cryotherapy</intervention_name>
    <description>Undergo oral cryotherapy</description>
    <arm_group_label>Arm I (acupuncture, acupressure, cryotherapy)</arm_group_label>
    <arm_group_label>Arm II (cryotherapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm I (acupuncture, acupressure, cryotherapy)</arm_group_label>
    <arm_group_label>Arm II (cryotherapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm I (acupuncture, acupressure, cryotherapy)</arm_group_label>
    <arm_group_label>Arm II (cryotherapy)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  GI cancer (primary esophagus, gastric, pancreas, biliary, liver, small bowel,&#xD;
             appendix, colon, rectal, anal, or gastrointestinal/pancreatic neuroendocrine tumor)&#xD;
             scheduled to receive a new start of fluorouracil (5-FU), oxaliplatin, +/- irinotecan&#xD;
             (fluorouracil/leucovorin calcium/oxaliplatin [FOLFOX],&#xD;
             fluorouracil/irinotecan/leucovorin calcium/oxaliplatin [FOLFIRINOX],&#xD;
             leucovorin/fluorouracil/oxaliplatin/irinotecan [FOLFOXIRI] regimens) with plan for &gt;=&#xD;
             3 months of therapy with the regimen. Chemotherapy can be given for neoadjuvant,&#xD;
             adjuvant, or palliative intent. 1 dose (cycle) of the intended regimen is permitted&#xD;
             prior to study enrollment.&#xD;
&#xD;
             **There is no limitation on the addition of a biologic agent to one of the above&#xD;
             chemotherapy regimens, including, but not limited to: bevacizumab, cetuximab,&#xD;
             panitumumab, trastuzumab, or the biosimilars of these agents&#xD;
&#xD;
          -  Age &gt;=18 years&#xD;
&#xD;
          -  Absolute neutrophil count &gt; 0.5 thousand/microL&#xD;
&#xD;
          -  Platelet count &gt; 20 thousand/microL&#xD;
&#xD;
          -  Not currently pregnant&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Baseline peripheral neuropathy from any cause&#xD;
&#xD;
          -  Planned oxaliplatin with capecitabine&#xD;
&#xD;
          -  Planned initial dose of oxaliplatin &lt; 100% of the standard regimen-specified dose. For&#xD;
             most regimens, this would be 85 mg/m^2 intravenously (IV) dosed every 14 days&#xD;
&#xD;
          -  Receipt of acupuncture treatment in the prior 3 months&#xD;
&#xD;
          -  Use of concomitant duloxetine for minimization of neuropathy&#xD;
&#xD;
          -  Psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements&#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>Stacey Cohen</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jon Daniels</last_name>
    <phone>206-606-6347</phone>
    <email>giresearch@seattlecca.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kate Jones</last_name>
    <phone>206-606-7350</phone>
    <email>giresearch@seattlecca.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jon Daniels</last_name>
      <phone>206-606-6347</phone>
      <email>giresearch@seattlecca.org</email>
    </contact>
    <contact_backup>
      <last_name>Kate Jones</last_name>
      <phone>206-606-7350</phone>
      <email>giresearch@seattlecca.org</email>
    </contact_backup>
    <investigator>
      <last_name>Stacey Cohen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>May 4, 2023</last_update_submitted>
  <last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Neuroendocrine Tumors</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
    <mesh_term>Stomach Neoplasms</mesh_term>
    <mesh_term>Digestive System Neoplasms</mesh_term>
    <mesh_term>Gastrointestinal Neoplasms</mesh_term>
    <mesh_term>Peripheral Nervous System Diseases</mesh_term>
  </condition_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/NCT04505553
org study id: RG1121095
secondary id: NCI-2020-05455
secondary id: P30CA015704
secondary id: 10559
nct id: NCT04505553
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
This phase II trial investigates how well oral cryotherapy plus acupressure and acupuncture
      compared with oral cryotherapy alone work in decreasing chemotherapy-induced peripheral
      neuropathy in patients with gastrointestinal cancer who are receiving oxaliplatin-based
      chemotherapy. Acupressure is the application of pressure or localized massage to specific
      sites on the body to control symptoms such as pain or nausea. Acupuncture is the technique of
      inserting thin needles through the skin at specific points on the body to control pain and
      other symptoms. Cryotherapy uses cold temperature such as oral ice chips to prevent
      abnormally increased pain sensation. Giving oral cryotherapy with acupressure and acupuncture
      may work better in decreasing chemotherapy-induced peripheral neuropathy from
      oxaliplatin-based chemotherapy in patients with gastrointestinal cancer compared to oral
      cryotherapy alone.
OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients undergo acupuncture during chemotherapy infusion on day 1 and fluorouracil
      pump disconnect on day 3 of each biweekly chemotherapy infusion over 12 weeks. Patients also
      undergo self-administered acupressure over 11 minutes daily for 12 weeks and undergo standard
      of care oral cryotherapy.

      ARM II: Patients undergo standard of care oral cryotherapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Severity of chemotherapy-induced peripheral neuropathy (CIPN)
time frame: At 3 months
description: Measured by the European Organization for Research and Treatment of Cancer (EORTC)-CIPN 20. Severity of CIPN will be summarized for each treatment arm, and treatment comparisons made via linear regression model with adjustment for baseline severity level. The EORTC QLQ-CIPN20 is a 20-item questionnaire that evaluates CIPN using 3 subscales that assess sensory (9 items), motor (8 items), and autonomic (3 items) symptoms and functioning with each item measured on a 1-4 scale (1, not at all; 4, very much). The sensory subscale raw scores range from 1 to 36. The CIPN-20 subscale raw scores are linearly converted to a 0-100 scale such that a high score corresponds to a worse condition or more symptoms.
measure: Incidence of grade 2 or higher CIPN
time frame: 3 months
description: Measured by Common Terminology Criteria for Adverse Events (CTCAE) version 5. Incidences of CIPN (grade 2 or higher), pain, fatigue, nausea, and anxiety will be compared between treatment arms using Chi-squared or Fisher's exact tests as appropriate.
measure: Severity of CIPN: Neuropen assessment of patients' perceived pain and pressure
time frame: 3 months
description: The Neuropen is used to assess touch and pressure perception as well as protective pain and sharpness sensation. Touch and pressure sensation will be assessed using a 10-g monofilament on the subject's dominant foot. Pain and subjective sharpness sensation will be assessed using the 40-g Neurotip on the dominant foot. Loss of pain and pressure sensation are associated with increased CIPN.
measure: Severity of CIPN: Tuning fork vibration sensation testing
time frame: 3 months
description: A study-specific 128-Hz tuning fork will be used to assess vibration sensation on dominant lower extremity and dominant upper extremity sites. If the patient feels the vibration for 15 seconds or longer, this is defined as normal. If the patient feels the vibration less than 15 seconds, this is defined as absent or decreased vibration sensation. Vibration sensation is lost sooner in CIPN, which means that shorter duration of vibration scores are associated with increased CIPN.
measure: Proportion of patients assigned to the intervention arm who complete 60% of acupuncture treatments
time frame: 3 months
description: Adherence to acupuncture treatment among patients in the intervention arm will be described as a proportion with 95% confidence interval. Reasons for treatment non-adherence and delivered dose intensity of chemotherapy will be noted.
measure: Incidence of pain, fatigue, nausea, and anxiety
time frame: 3 months
description: Measured by patient-reported (National Cancer Institute [NCI] Patient Reported Outcomes [PRO]-CTCAE, Brief Pain Inventory [BPI], oral dysesthesia) and provider-assessed (CTCAE version 5) grading scales.
arm group label: Arm I (acupuncture, acupressure, cryotherapy)
arm group type: Experimental
description: Patients undergo acupuncture during chemotherapy infusion on day 1 and fluorouracil pump disconnect on day 3 of each biweekly chemotherapy infusion over 12 weeks. Patients also undergo self-administered acupressure over 11 minutes daily for 12 weeks and undergo standard of care oral cryotherapy.
arm group label: Arm II (cryotherapy)
arm group type: Active Comparator
description: Patients undergo standard of care oral cryotherapy.
intervention type: Procedure
intervention name: Acupuncture Therapy
description: Undergo acupuncture
arm group label: Arm I (acupuncture, acupressure, cryotherapy)
other name: Acupuncture
intervention type: Procedure
intervention name: Acupressure Therapy
description: Undergo acupressure
arm group label: Arm I (acupuncture, acupressure, cryotherapy)
other name: acupressure
other name: Ischemic Compression
intervention type: Procedure
intervention name: Oral Cryotherapy
description: Undergo oral cryotherapy
arm group label: Arm I (acupuncture, acupressure, cryotherapy)
arm group label: Arm II (cryotherapy)
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Arm I (acupuncture, acupressure, cryotherapy)
arm group label: Arm II (cryotherapy)
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Arm I (acupuncture, acupressure, cryotherapy)
arm group label: Arm II (cryotherapy)
other name: Quality of Life Assessment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stacey Cohen
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
last name: Jon Daniels
phone: 206-606-6347
email: giresearch@seattlecca.org
last name: Kate Jones
phone: 206-606-7350
email: giresearch@seattlecca.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Neuroendocrine Tumors
mesh term: Pancreatic Neoplasms
mesh term: Esophageal Neoplasms
mesh term: Stomach Neoplasms
mesh term: Digestive System Neoplasms
mesh term: Gastrointestinal Neoplasms
mesh term: Peripheral Nervous System Diseases
sharing ipd: No