<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/NCT01684904</url>
  </required_header>
  <id_info>
    <org_study_id>5120054</org_study_id>
    <nct_id>NCT01684904</nct_id>
  </id_info>
  <brief_title>Proton Therapy for Esophageal Cancer</brief_title>
  <official_title>A Phase II Trial of Proton Chemotherapy (PCT) for Resectable Esophageal or Esophagogastric Junction Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Loma Linda University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Loma Linda University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The goal of this phase II study is to investigate the feasibility, toxicity and efficacy of a&#xD;
      regimen incorporating a proven systemic regimen, carboplatin /paclitaxel, with conformal&#xD;
      proton modality, followed by definitive surgery. In most combined-modality trials to date,&#xD;
      chemotherapy regimens have included cisplatin, usually in conjunction with 5-fluorouracil.&#xD;
&#xD;
      In designing the regimen, the investigators attempt to improve on the standard&#xD;
      cisplatin/5-fluorouracil regimen in several ways. First, full-dose paclitaxel is added to the&#xD;
      regimen. This agent has activity against advanced esophageal cancer and is also a potent&#xD;
      radiosensitizer. Second, the substitution of carboplatin for cisplatin has resulted in&#xD;
      reduced toxicity of various combination regimens similar to that used by CROSS trial and&#xD;
      allows for easier administration in the outpatient setting.4 Third, for localized esophageal&#xD;
      cancer, dose distribution patterns achievable with proton beam could potentially offer&#xD;
      important clinical advantages relative to those achievable with x-rays (photons).19 Based on&#xD;
      this, the investigators believe that this study should be conducted with the radiation&#xD;
      modality that offers the best dosimetry achievable at our institution.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 20, 2013</start_date>
  <completion_date type="Anticipated">August 2032</completion_date>
  <primary_completion_date type="Anticipated">August 2027</primary_completion_date>
  <phase>N/A</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>To assess overall survival of patients treated with proton-chemotherapy (PCT) followed by surgery in patients with resectable primary esophageal or esophagogastric cancer</measure>
    <time_frame>The major analysis for reporting the initial results of treatment will be undertaken when each patient has been potentially followed for a minimum of 3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events as a measure of safety and tolerability</measure>
    <time_frame>The major analysis for reporting the initial results of treatment will be undertaken when each patient has been potentially followed for a minimum of 3 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">38</enrollment>
  <condition>Esophagus Cancer</condition>
  <arm_group>
    <arm_group_label>Proton radiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Proton radiation</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Proton radiation</intervention_name>
    <arm_group_label>Proton radiation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically confirmed primary squamous cell or adenocarcinoma of the esophagus that&#xD;
             involves the mid, distal or esophagogastric junction. The cancer may involve the&#xD;
             stomach up to 5 cm.&#xD;
&#xD;
          -  Endoscopy with biopsy&#xD;
&#xD;
          -  Stage T1N102, T2-3N0-2 according to the American Joint Committee on Cancer (AJCC) 7th&#xD;
             edition staging, based upon the following minimum diagnostic work-up:&#xD;
&#xD;
        History/physical examination with documentation of patient's weight within 30 days of&#xD;
        registration&#xD;
&#xD;
        Chest/Abdominal/Pelvic contrast CT within 56 days of registration&#xD;
&#xD;
        Whole body PET/CT within 56 days of registration&#xD;
&#xD;
        Endoscopic ultrasound&#xD;
&#xD;
        Patients may have regional adenopathy including para-esophageal, gastric, gastroheptaic and&#xD;
        celiac nodes. If celiac adenopathy present, it must be ≤ 2cm.&#xD;
&#xD;
        Patients with tumors at the level of the carina or above should undergo bronchoscopy to&#xD;
        exclude fistula&#xD;
&#xD;
        Pulmonary function test (including routine spirometry and DLCO) within 60 days prior to&#xD;
        registration&#xD;
&#xD;
        Serum creatinine ≤ 2 x the upper limit of normal within 4 weeks of registration&#xD;
&#xD;
        Na, K, BUN, Glucose within 4 weeks prior to registration&#xD;
&#xD;
        CBC/differential within 4 weeks prior to registration with adequate bone marrow function,&#xD;
        defined as follows:&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3&#xD;
&#xD;
          -  Platelets ≥ 100,000 cell/mm3&#xD;
&#xD;
          -  Hemoglobin ≥ 8.0 g/dl (Note: the use of transfusion or other intervention to achieve&#xD;
             Hgb ≥ 8.0 is acceptable.)&#xD;
&#xD;
        Adequate liver function, defined as total bilirubin ≤ 1.5 x upper limit of normal, AST ≤ 3&#xD;
        x the upper limit of normal within 4 weeks of registration&#xD;
&#xD;
        Age ≥ 18&#xD;
&#xD;
        Zubrod performance status 0-2 within 4 weeks of registration&#xD;
&#xD;
        Surgical consultation to confirm that patient will be able to undergo curative resection&#xD;
        after completion of PCT prior to registration&#xD;
&#xD;
        For women of childbearing potential, a negative serum pregnancy test within 14 days prior&#xD;
        to registration&#xD;
&#xD;
        Women of childbearing potential and male participants must practice adequate contraception&#xD;
        while on study&#xD;
&#xD;
        Patient must sign study specific informed consent prior to study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients with cervical esophageal carcinoma&#xD;
&#xD;
        Patients with T1N0 disease and T4 disease&#xD;
&#xD;
        Prior radiation for esophageal cancer or prior chest radiotherapy&#xD;
&#xD;
        Prior chemotherapy for esophageal cancer&#xD;
&#xD;
        Evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi&#xD;
&#xD;
        Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a&#xD;
        minimum of 2 years ( e.g. carcinoma in situ of breast, oral cavity, or cervix are&#xD;
        permissible)&#xD;
&#xD;
        Prior radiotherapy that would results in overlap of radiation fields&#xD;
&#xD;
        Medical contraindications to esophagectomy&#xD;
&#xD;
        Prior allergic reaction to paclitaxel or carboplatin&#xD;
&#xD;
        Severe, active co-morbidity that may impact survival&#xD;
&#xD;
        Pregnancy, nursing women, or women of child bearing potential, and men who are sexually&#xD;
        active and not willing/able to use medically acceptable forms of contraception&#xD;
&#xD;
        -&#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>Gary Yang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>gyang@llu.edu</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sandi Teichman or Miriam Hernandez Study Coordinators, RN</last_name>
    <phone>909-558-4000</phone>
    <phone_ext>55240 / 88231</phone_ext>
    <email>scteichm@llu.edu; mvhernandez@llu.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Gary Yang, MD</last_name>
    <phone>909-558-4000</phone>
    <phone_ext>15689</phone_ext>
    <email>gyang@llu.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Loma Linda University Medical Center</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <zip>92354</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gary Yang, MD</last_name>
      <phone>909-558-4280</phone>
      <email>gyang@llu.edu</email>
    </contact>
    <investigator>
      <last_name>Gary Yang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <last_update_submitted>February 20, 2023</last_update_submitted>
  <last_update_submitted_qc>February 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Loma Linda University</investigator_affiliation>
    <investigator_full_name>Gary Yang, MD</investigator_full_name>
    <investigator_title>MD, Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophageal Neoplasms</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/NCT01684904
org study id: 5120054
nct id: NCT01684904
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
The goal of this phase II study is to investigate the feasibility, toxicity and efficacy of a
      regimen incorporating a proven systemic regimen, carboplatin /paclitaxel, with conformal
      proton modality, followed by definitive surgery. In most combined-modality trials to date,
      chemotherapy regimens have included cisplatin, usually in conjunction with 5-fluorouracil.

      In designing the regimen, the investigators attempt to improve on the standard
      cisplatin/5-fluorouracil regimen in several ways. First, full-dose paclitaxel is added to the
      regimen. This agent has activity against advanced esophageal cancer and is also a potent
      radiosensitizer. Second, the substitution of carboplatin for cisplatin has resulted in
      reduced toxicity of various combination regimens similar to that used by CROSS trial and
      allows for easier administration in the outpatient setting.4 Third, for localized esophageal
      cancer, dose distribution patterns achievable with proton beam could potentially offer
      important clinical advantages relative to those achievable with x-rays (photons).19 Based on
      this, the investigators believe that this study should be conducted with the radiation
      modality that offers the best dosimetry achievable at our institution.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To assess overall survival of patients treated with proton-chemotherapy (PCT) followed by surgery in patients with resectable primary esophageal or esophagogastric cancer
time frame: The major analysis for reporting the initial results of treatment will be undertaken when each patient has been potentially followed for a minimum of 3 months
measure: Number of participants with adverse events as a measure of safety and tolerability
time frame: The major analysis for reporting the initial results of treatment will be undertaken when each patient has been potentially followed for a minimum of 3 months
arm group label: Proton radiation
arm group type: Experimental
description: Proton radiation
intervention type: Radiation
intervention name: Proton radiation
arm group label: Proton radiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gary Yang, MD
role: Principal Investigator
affiliation: gyang@llu.edu
last name: Sandi Teichman or Miriam Hernandez Study Coordinators, RN
phone: 909-558-4000
phone ext: 55240 / 88231
email: scteichm@llu.edu; mvhernandez@llu.edu
last name: Gary Yang, MD
phone: 909-558-4000
phone ext: 15689
email: gyang@llu.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Loma Linda University
investigator full name: Gary Yang, MD
investigator title: MD, Principal Investigator
mesh term: Esophageal Neoplasms
sharing ipd: No