<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/NCT03255434</url>
  </required_header>
  <id_info>
    <org_study_id>ICM-URC2016/27</org_study_id>
    <nct_id>NCT03255434</nct_id>
  </id_info>
  <brief_title>LEAn Body Mass Normalization of OXaliplatin Based Chemotherapy</brief_title>
  <acronym>LEANOX</acronym>
  <official_title>LEAn Body Mass Normalization of OXaliplatin Based Chemotherapy for Stage III Colon Cancer Patients Treated in Adjuvant Setting: Impact on Oxaliplatin-induced Sensitive Neurotoxicity. A Multicenter Phase II Randomized Trial (LEANOX)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut du Cancer de Montpellier - Val d'Aurelle</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut du Cancer de Montpellier - Val d'Aurelle</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cytotoxic chemotherapy is usually scaled to the body surface area (BSA), and is currently not&#xD;
      adjusted to the body proportions of lean and fat (i.e. body composition) of individual&#xD;
      patients. Patients with low muscle mass behave like patients &quot;overdosed&quot; with chemotherapy&#xD;
      resulted in dose-limiting toxicities (e.g. dose reductions, treatment delays or permanent&#xD;
      treatment discontinuation), independently of the patient's weight.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Adjuvant chemotherapy with fluoropyrimidines and Oxaliplatin is the current worldwide&#xD;
      standard of care for stage III colorectal cancer (CRC). This regimen leads to significant&#xD;
      cost, toxicity, and patient inconvenience. Oxaliplatin induces two distinct forms of&#xD;
      neuropathy: a common acute syndrome that is transient (dysesthesia, contractures and&#xD;
      numbness) and a dose-limiting chronic sensory neurotoxicity that is cumulative. Neurotoxicity&#xD;
      is common; it affects 80% of patients and becomes chronic in 15-20% of cases, sometimes&#xD;
      irreversibly. Chronic neurotoxicity can severely affect everyday life activities. To date,&#xD;
      neuromodulators agents have failed to prevent neurotoxicity and Stop &amp; Go strategies,&#xD;
      intended to decrease the cumulative dose of Oxaliplatin administrated, are more appropriate&#xD;
      for palliative treatment of advanced CRC. Recent data support the plausibility of a shorter&#xD;
      duration of adjuvant treatment without loss of efficacy. This hypothesis is tested in several&#xD;
      international trials.&#xD;
&#xD;
      Cytotoxic chemotherapy is usually scaled to the body surface area (BSA), and is currently not&#xD;
      adjusted to the body proportions of lean and fat (i.e. body composition) of individual&#xD;
      patients. The impact of body composition on drug metabolism is however well known: i.e.&#xD;
      anesthetics accumulate in adipose tissue and specific precautions are essential to avoid&#xD;
      overdose. Concerning chemotherapies, the lean body mass (LBM) may be the salient feature&#xD;
      defining drug metabolism. A theme is emerging from recent studies: in patients with breast&#xD;
      cancer and treated with 5-FU (whose dosage was calculated from the body surface), severe&#xD;
      depletion of the LBM is a powerful predictor of excessive toxicity. Indeed, depletion of the&#xD;
      LBM, as precisely defined by computed tomography, is a unique predictor of clinically&#xD;
      unacceptable toxicity. Low LBM was shown to be a significant predictor of dose-limiting&#xD;
      toxicity (DLT) in CRC patients administered 5-FU using a conventional BSA-based dosing and&#xD;
      DLT was concentrated in patients receiving &gt;20 mg 5FU/kg LBM. Two cohorts of CRC patients&#xD;
      treated with Oxaliplatin showed that overall DLTs, and specifically Oxaliplatin-due&#xD;
      neuropathy, occurred mostly in patients who receive &gt; 3.09 mg/Oxaliplatin/kg LBM. Although,&#xD;
      preliminary findings are available in hepatocellular carcinoma, the area under the&#xD;
      concentration time curve (AUC) of Sorafenib cancer therapy was doubled in patients with&#xD;
      depleted LBM (102.4 vs. 53.7ng/mL.h), which seem of interest. Patients with low muscle mass&#xD;
      behave like patients &quot;overdosed&quot; with chemotherapy resulted in dose-limiting toxicities (e.g.&#xD;
      dose reductions, treatment delays or permanent treatment discontinuation), independently of&#xD;
      the patient's weight.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 1, 2017</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Actual">July 28, 2022</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>Evaluation of neurotoxicity associated with Oxaliplatin</measure>
    <time_frame>through study completion, an average of 5 years</time_frame>
    <description>Neurotoxicity assessment</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">160</enrollment>
  <condition>Stage III Colon Cancer</condition>
  <arm_group>
    <arm_group_label>Folfox 4</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard FOLFOX4: Oxaliplatin and simplified LV5FU2 Dose of oxaliplatin 85mg/m²</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Folfox 4 LBM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Adapted FOLFOX4: Oxaliplatin and simplified LV5FU2 Dose of oxaliplatin allocated according to lean body mass (LBM)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Simplified FOLFOX 4 regimen: Association of Oxaliplatin (85 mg/m² ) + simplified LV5FU2 Length of a cycle : 2 days Interval between 2 cycles : 2 weeks (D1=D15) Expected number of cycles: 12</description>
    <arm_group_label>Folfox 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin LBM</intervention_name>
    <description>Simplified FOLFOX 4 regimen: Association of Oxaliplatin (LBM) + simplified LV5FU2</description>
    <arm_group_label>Folfox 4 LBM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: more than 18 years old up to 75 years old including. Histologically confirmed&#xD;
             adenocarcinoma of the colon.&#xD;
&#xD;
          -  Has undergone a curative resection for stage III colon cancer.&#xD;
&#xD;
          -  Scheduled to receive 6 months of Oxaliplatin-based adjuvant chemotherapy at a dose of&#xD;
             85 mg/m² of Oxaliplatin every 2 weeks (simplified FOLFOX 4 regimen).&#xD;
&#xD;
          -  The following laboratory values obtained ≤ 28 days prior to inclusion:&#xD;
&#xD;
        WBC ≥ 3000/mm3; ANC ≥1500/mm3; PLT ≥100,000/mm3; HgB ≥10.0g/dl; Total bilirubin ≤1.5 x&#xD;
        upper normal limit (UNL); Serum creatinine ≤1.5 x UNL; Serum calcium ≤ 1.2 x UNL; Serum&#xD;
        magnesium ≤ 1.2 x UNL.&#xD;
&#xD;
          -  Central venous access line present or patient scheduled to have a central line placed&#xD;
             prior to starting chemotherapy or the treatment protocol.&#xD;
&#xD;
          -  Negative pregnancy test (serum or urine) done ≤ 7 days prior to registration, for&#xD;
             women of childbearing potential only.&#xD;
&#xD;
          -  Ability to complete questionnaire(s) by themselves or with assistance.&#xD;
&#xD;
          -  ECOG Performance Status (PS) of 0, 1 for patients until 70 years old included and ECOG&#xD;
             PS of 0 for patients between 70 to 75 years old included.&#xD;
&#xD;
          -  Has provided informed written consent.&#xD;
&#xD;
          -  Patient willing to provide blood sample for research purposes&#xD;
&#xD;
          -  Patient affiliated to a French social security system&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Men or women of childbearing potential who are unwilling to employ adequate&#xD;
             contraception since this study involves agents that have known genotoxic, mutagenic&#xD;
             and teratogenic effects&#xD;
&#xD;
          -  Pre-existing peripheral neuropathy of any grade.&#xD;
&#xD;
          -  Prior treatment with neurotoxic chemotherapy such as Oxaliplatin, cisplatin, taxanes,&#xD;
             or vinca alkaloids.&#xD;
&#xD;
          -  Treatment with 1) the anticonvulsants carbamazepine (e.g., Tegretol®), phenytoin&#xD;
             (e.g., Dilantin®), valproic acid (e.g. Depakine®), gabapentin (Neurontin®); pregabalin&#xD;
             (Lyrica®); 2) the following neurotropic agents: venlafaxine (Effexor®), desvenlafaxine&#xD;
             (Pristiq®), milnacipran (Savella®) or duloxetine (Cymbalta®); 3) Tricyclic&#xD;
             antidepressants (such as amitryptilline) or 4) any other agent specifically given to&#xD;
             prevent or treat neuropathy.&#xD;
&#xD;
          -  Family history of a genetic/familial neuropathy.&#xD;
&#xD;
          -  Participation in another medication trial within 30 days prior to study entry&#xD;
&#xD;
          -  Legal incapacity or physical, psychological social or geographical status interfering&#xD;
             with the patient's ability to sign the informed consent or to terminate the study&#xD;
&#xD;
          -  History of other solid tumor in 3 years before the inclusion, excepted of cancer in&#xD;
             situ of the cervix and skin cancer (basal or squamous cell) treated and controlled.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>marc YCHOU</last_name>
    <role>Study Director</role>
    <affiliation>Institut régional du Cancer de Montpellier</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Européen</name>
      <address>
        <city>Marseille</city>
        <state>Bouches Du Rhône</state>
        <zip>13003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier régional et universitaire de Montpellier</name>
      <address>
        <city>Montpellier</city>
        <state>Hérault</state>
        <zip>34000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Nancy</name>
      <address>
        <city>Vandœuvre-lès-Nancy</city>
        <state>Lorraine</state>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Insitut de Cancérologie de Lorraine</name>
      <address>
        <city>Vandœuvre-lès-Nancy</city>
        <state>Meurthe-et-Moselle,</state>
        <zip>54519</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint-Jean</name>
      <address>
        <city>Perpignan</city>
        <state>Pyrénées-orientales</state>
        <zip>66000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre François Baclesse</name>
      <address>
        <city>Caen</city>
        <zip>14076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU La TIMONE</name>
      <address>
        <city>Marseille</city>
        <zip>13</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut regional du Cancer - Val d Aurelle</name>
      <address>
        <city>Montpellier</city>
        <zip>34298</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP Hôpital Saint-Louis</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Eugène Marquis</name>
      <address>
        <city>Rennes</city>
        <zip>35042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Paul Strauss</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <last_update_submitted>June 15, 2023</last_update_submitted>
  <last_update_submitted_qc>June 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 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>Colonic 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>
  <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/NCT03255434
org study id: ICM-URC2016/27
nct id: NCT03255434
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Cytotoxic chemotherapy is usually scaled to the body surface area (BSA), and is currently not
      adjusted to the body proportions of lean and fat (i.e. body composition) of individual
      patients. Patients with low muscle mass behave like patients "overdosed" with chemotherapy
      resulted in dose-limiting toxicities (e.g. dose reductions, treatment delays or permanent
      treatment discontinuation), independently of the patient's weight.
Adjuvant chemotherapy with fluoropyrimidines and Oxaliplatin is the current worldwide
      standard of care for stage III colorectal cancer (CRC). This regimen leads to significant
      cost, toxicity, and patient inconvenience. Oxaliplatin induces two distinct forms of
      neuropathy: a common acute syndrome that is transient (dysesthesia, contractures and
      numbness) and a dose-limiting chronic sensory neurotoxicity that is cumulative. Neurotoxicity
      is common; it affects 80% of patients and becomes chronic in 15-20% of cases, sometimes
      irreversibly. Chronic neurotoxicity can severely affect everyday life activities. To date,
      neuromodulators agents have failed to prevent neurotoxicity and Stop & Go strategies,
      intended to decrease the cumulative dose of Oxaliplatin administrated, are more appropriate
      for palliative treatment of advanced CRC. Recent data support the plausibility of a shorter
      duration of adjuvant treatment without loss of efficacy. This hypothesis is tested in several
      international trials.

      Cytotoxic chemotherapy is usually scaled to the body surface area (BSA), and is currently not
      adjusted to the body proportions of lean and fat (i.e. body composition) of individual
      patients. The impact of body composition on drug metabolism is however well known: i.e.
      anesthetics accumulate in adipose tissue and specific precautions are essential to avoid
      overdose. Concerning chemotherapies, the lean body mass (LBM) may be the salient feature
      defining drug metabolism. A theme is emerging from recent studies: in patients with breast
      cancer and treated with 5-FU (whose dosage was calculated from the body surface), severe
      depletion of the LBM is a powerful predictor of excessive toxicity. Indeed, depletion of the
      LBM, as precisely defined by computed tomography, is a unique predictor of clinically
      unacceptable toxicity. Low LBM was shown to be a significant predictor of dose-limiting
      toxicity (DLT) in CRC patients administered 5-FU using a conventional BSA-based dosing and
      DLT was concentrated in patients receiving >20 mg 5FU/kg LBM. Two cohorts of CRC patients
      treated with Oxaliplatin showed that overall DLTs, and specifically Oxaliplatin-due
      neuropathy, occurred mostly in patients who receive > 3.09 mg/Oxaliplatin/kg LBM. Although,
      preliminary findings are available in hepatocellular carcinoma, the area under the
      concentration time curve (AUC) of Sorafenib cancer therapy was doubled in patients with
      depleted LBM (102.4 vs. 53.7ng/mL.h), which seem of interest. Patients with low muscle mass
      behave like patients "overdosed" with chemotherapy resulted in dose-limiting toxicities (e.g.
      dose reductions, treatment delays or permanent treatment discontinuation), independently of
      the patient's weight.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluation of neurotoxicity associated with Oxaliplatin
time frame: through study completion, an average of 5 years
description: Neurotoxicity assessment
arm group label: Folfox 4
arm group type: Active Comparator
description: Standard FOLFOX4: Oxaliplatin and simplified LV5FU2 Dose of oxaliplatin 85mg/m²
arm group label: Folfox 4 LBM
arm group type: Experimental
description: Adapted FOLFOX4: Oxaliplatin and simplified LV5FU2 Dose of oxaliplatin allocated according to lean body mass (LBM)
intervention type: Drug
intervention name: Oxaliplatin
description: Simplified FOLFOX 4 regimen: Association of Oxaliplatin (85 mg/m² ) + simplified LV5FU2 Length of a cycle : 2 days Interval between 2 cycles : 2 weeks (D1=D15) Expected number of cycles: 12
arm group label: Folfox 4
intervention type: Drug
intervention name: Oxaliplatin LBM
description: Simplified FOLFOX 4 regimen: Association of Oxaliplatin (LBM) + simplified LV5FU2
arm group label: Folfox 4 LBM
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: marc YCHOU
role: Study Director
affiliation: Institut régional du Cancer de Montpellier
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Colonic Neoplasms
mesh term: Oxaliplatin
sharing ipd: No