<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/NCT02215083</url>
  </required_header>
  <id_info>
    <org_study_id>ERMC 13-32</org_study_id>
    <nct_id>NCT02215083</nct_id>
  </id_info>
  <brief_title>L-glutamine Supplementation to Alleviate Symptoms of Taxane-Induced Neuropathy in Patients With Breast Cancer</brief_title>
  <official_title>L-glutamine Supplementation to Alleviate Symptoms of Taxane-Induced Neuropathy in Patients With Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eastern Regional Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>TSPC America, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Eastern Regional Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to determine whether daily, high-dose administration of&#xD;
      l-glutamine can reduce numbness and tingling caused by a taxane chemotherapy in patients with&#xD;
      breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      L-glutamine has previously been shown to help reduce the incidence of numbness and tingling&#xD;
      in patients with breast cancer who are receiving taxane chemotherapies. However, no study to&#xD;
      date looks at the effect of l-glutamine given after this numbness and tingling (called&#xD;
      'perihperhal neuropathy') has already occurred. We hypothesize that administration of this&#xD;
      amino acid in l-glutamine naïve patients will result in a measureable reduction of their&#xD;
      taxane-induced neuropathy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Insufficient Patient Population&#xD;
  </why_stopped>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total sensory neuropathy (area under the curve [AUC]) as measured by the EORTC QLQ-CIPN20 at baseline and week 9</measure>
    <time_frame>nine weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess Quality of Life</measure>
    <time_frame>nine weeks</time_frame>
    <description>Motor neuropathy as measured by the EORTC QLQ-CIPN20 at baseline and week 9&#xD;
Autonomic symptoms and functioning as measured by the EORTC QLQ-CIPN20 at baseline and week 9&#xD;
Overall quality of life as measured by the EORTC-30 questionnaire at baseline, 3 weeks, 6 weeks, and week 9&#xD;
Pain severity as measured by the Visual Analog Numeric Pain Scale at baseline, week 3, week 6 and week 9&#xD;
Objective assessment performed by Physical Therapy Department as measured by the Functional Gait Assessment at baseline and week 9&#xD;
Frequency and severity of adverse events reported by the patient in the Symptom Experience Diary and evaluated through clinical assessment by NCI CTCAE v3.0</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Observe progression-free survival for 36 months post-intervention with l-glutamine supplementation</measure>
    <time_frame>40 months</time_frame>
    <description>Quarterly record review to determine progression-free survival for 36 months post-l-glutamine intervention</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Peripheral Neuropathy</condition>
  <arm_group>
    <arm_group_label>L-Glutamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients will receive 20-30 grams of l-glutamine daily for 9 weeks (+/- 1 week)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>L-glutamine</intervention_name>
    <description>10,000mg by mouth, twice daily for nine weeks (± 7 days) with one permitted dose escalation to a maximum of 10,000mg by mouth three times daily.</description>
    <arm_group_label>L-Glutamine</arm_group_label>
    <other_name>Glutamine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Biopsy proven adenocarcinoma of the breast&#xD;
&#xD;
          -  Received at least one prior taxane-containing chemotherapy regimen which resulted in&#xD;
             persistent taxane-induced peripheral neuropathy&#xD;
&#xD;
          -  Anticipated survival of at least 6 months&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 0, 1, or 2&#xD;
&#xD;
          -  The patient must have screening laboratory: Transaminases&lt;2.5 x upper limit of normal;&#xD;
             total bilirubin &lt;2.0; creatinine &lt;1.5&#xD;
&#xD;
          -  Neuropathy onset from taxane administration no more than 18 months from date enrolled&#xD;
             in trial&#xD;
&#xD;
          -  Willingness to adhere to supplemental regimen of l-glutamine 10,000mg taken orally&#xD;
             twice daily, with one potential dose escalation to 10,000mg taken orally three times&#xD;
             daily.&#xD;
&#xD;
          -  Grade I-III sensory peripheral neuropathy related to prior taxane use as assessed by&#xD;
             their treating oncologist at Eastern Regional Medical Center&#xD;
&#xD;
          -  Able to give informed consent for protocol participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants are not able to understand or provide written informed consent.&#xD;
&#xD;
          -  The research team deems that the participant may not be able to follow the study&#xD;
             protocol.&#xD;
&#xD;
          -  Current diagnosis of bipolar disorder or other manic state&#xD;
&#xD;
          -  Prior use of l-glutamine for prevention or empirical treatment of taxane-induced&#xD;
             sensory peripheral neuropathy&#xD;
&#xD;
          -  Prior treatment with a platinum chemotherapy&#xD;
&#xD;
          -  Concurrent use of physical therapy interventions such as the 'Rebuilder', chiropractic&#xD;
             care, acupuncture, or other modalities specifically targeting peripheral neuropathy&#xD;
&#xD;
          -  Concomitant use of nutraceutical supplements which may mitigate symptoms of&#xD;
             taxane-induced peripheral neuropathy including B-Complex vitamins, alpha-lipoic acid,&#xD;
             vitamin E, acetyl-l-carnitine, intramuscular B12 injections, fish oil, etc… during&#xD;
             study&#xD;
&#xD;
          -  Renal insufficiency : serum creatinine of &gt;1.5 mg /dl&#xD;
&#xD;
          -  Hepatic insufficiency: transaminases &gt; 2.5 x upper limit of normal due to isolated&#xD;
             reports of possible hepatic encephalopathy&#xD;
&#xD;
          -  New prescription or dose adjustment of current medication for the treatment of&#xD;
             peripheral neuropathy such as gabapentin or Lyrica within the past 30 days.&#xD;
&#xD;
          -  Pre-existing sensory peripheral neuropathy from other comorbid conditions such as&#xD;
             diabetes or alcoholism&#xD;
&#xD;
          -  Current serious infection or other serious medical condition&#xD;
&#xD;
          -  Currently active second malignancy other than nonmelanatous skin cancer or carcinoma&#xD;
             in situ of the cervix&#xD;
&#xD;
          -  Pregnant or lactating female (pre-menopausal females will undergo pregnancy test prior&#xD;
             to administration of protocol drugs throughout treatment cycles during this study)&#xD;
&#xD;
          -  Acetaminophen use exceeding 2 g per day-includes use of acetaminophen-containing pain&#xD;
             medications such as Percocet.&#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>Jack Medendorp</last_name>
    <role>Study Director</role>
    <affiliation>Eastern Regional Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Eastern Regional Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Stubblefield MD, Vahdat LT, Balmaceda CM, Troxel AB, Hesdorffer CS, Gooch CL. Glutamine as a neuroprotective agent in high-dose paclitaxel-induced peripheral neuropathy: a clinical and electrophysiologic study. Clin Oncol (R Coll Radiol). 2005 Jun;17(4):271-6. doi: 10.1016/j.clon.2004.11.014.</citation>
    <PMID>15997923</PMID>
  </reference>
  <reference>
    <citation>Vahdat L, Papadopoulos K, Lange D, Leuin S, Kaufman E, Donovan D, Frederick D, Bagiella E, Tiersten A, Nichols G, Garrett T, Savage D, Antman K, Hesdorffer CS, Balmaceda C. Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res. 2001 May;7(5):1192-7.</citation>
    <PMID>11350883</PMID>
  </reference>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>July 10, 2017</last_update_submitted>
  <last_update_submitted_qc>July 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>peripheral neuropathy</keyword>
  <keyword>breast cancer</keyword>
  <keyword>taxane induced peripheral neuropathy</keyword>
  <keyword>chemotherapy induced peripheral neuropathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Nervous System Diseases</mesh_term>
  </condition_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/NCT02215083
org study id: ERMC 13-32
nct id: NCT02215083
lead sponsor: 
collaborator: 
has dmc: No
The purpose of the study is to determine whether daily, high-dose administration of
      l-glutamine can reduce numbness and tingling caused by a taxane chemotherapy in patients with
      breast cancer.
L-glutamine has previously been shown to help reduce the incidence of numbness and tingling
      in patients with breast cancer who are receiving taxane chemotherapies. However, no study to
      date looks at the effect of l-glutamine given after this numbness and tingling (called
      'perihperhal neuropathy') has already occurred. We hypothesize that administration of this
      amino acid in l-glutamine naïve patients will result in a measureable reduction of their
      taxane-induced neuropathy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Total sensory neuropathy (area under the curve [AUC]) as measured by the EORTC QLQ-CIPN20 at baseline and week 9
time frame: nine weeks
measure: Assess Quality of Life
time frame: nine weeks
description: Motor neuropathy as measured by the EORTC QLQ-CIPN20 at baseline and week 9
Autonomic symptoms and functioning as measured by the EORTC QLQ-CIPN20 at baseline and week 9
Overall quality of life as measured by the EORTC-30 questionnaire at baseline, 3 weeks, 6 weeks, and week 9
Pain severity as measured by the Visual Analog Numeric Pain Scale at baseline, week 3, week 6 and week 9
Objective assessment performed by Physical Therapy Department as measured by the Functional Gait Assessment at baseline and week 9
Frequency and severity of adverse events reported by the patient in the Symptom Experience Diary and evaluated through clinical assessment by NCI CTCAE v3.0
measure: Observe progression-free survival for 36 months post-intervention with l-glutamine supplementation
time frame: 40 months
description: Quarterly record review to determine progression-free survival for 36 months post-l-glutamine intervention
arm group label: L-Glutamine
arm group type: Experimental
description: All patients will receive 20-30 grams of l-glutamine daily for 9 weeks (+/- 1 week)
intervention type: Dietary Supplement
intervention name: L-glutamine
description: 10,000mg by mouth, twice daily for nine weeks (± 7 days) with one permitted dose escalation to a maximum of 10,000mg by mouth three times daily.
arm group label: L-Glutamine
other name: Glutamine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jack Medendorp
role: Study Director
affiliation: Eastern Regional Medical Center
facility: 
country: United States
citation: Stubblefield MD, Vahdat LT, Balmaceda CM, Troxel AB, Hesdorffer CS, Gooch CL. Glutamine as a neuroprotective agent in high-dose paclitaxel-induced peripheral neuropathy: a clinical and electrophysiologic study. Clin Oncol (R Coll Radiol). 2005 Jun;17(4):271-6. doi: 10.1016/j.clon.2004.11.014.
PMID: 15997923
citation: Vahdat L, Papadopoulos K, Lange D, Leuin S, Kaufman E, Donovan D, Frederick D, Bagiella E, Tiersten A, Nichols G, Garrett T, Savage D, Antman K, Hesdorffer CS, Balmaceda C. Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res. 2001 May;7(5):1192-7.
PMID: 11350883
responsible party type: Sponsor
mesh term: Peripheral Nervous System Diseases