<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/NCT01683422</url>
  </required_header>
  <id_info>
    <org_study_id>5110324</org_study_id>
    <nct_id>NCT01683422</nct_id>
  </id_info>
  <brief_title>Chemotherapy Plus Proton-chemotherapy for Locally Advanced Pancreatic Cancer</brief_title>
  <official_title>A Phase II Trial of Gemcitabine and Erlotinib (GE) Plus Proton-chemotherapy (PCT) and Capox for Locally Advanced Pancreatic Cancer (LAPC)</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current trial will provide important data on the recurrence rates and patterns of failure&#xD;
      using state of the art target agent, chemotherapy and proton beam technology for patients&#xD;
      with Locally Advanced Pancreatic Cancer (LAPC). A median survival of 10 months or greater&#xD;
      would be considered evidence of a regimen potentially worthy of further study as a new&#xD;
      treatment paradigm in one arm in a future phase III trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The current trend toward using the biology of the disease as it becomes evident over a period&#xD;
      of chemotherapy to better select patients who will benefit from chemoradiotherapy (CRT) seems&#xD;
      to be the most pragmatic way to proceed, until we have a better means of predicting tumor&#xD;
      behavior and more active systemic agents. This has led to increased interest in treatment&#xD;
      regimens incorporating induction chemotherapy with target agent followed by CRT and&#xD;
      additional chemotherapy for diseases that carry a high risk for systemic relapse.&#xD;
&#xD;
      The PA.3 trial was the first phase III trial in advanced pancreatic cancer to show a survival&#xD;
      advantage with the addition of a second drug, in this case the oral Epidermal growth factor&#xD;
      receptor (EGFR) inhibitor Erlotinib to gemcitabine. The approval provides an important proof&#xD;
      of concept regarding the use of newer &quot;targeted&quot; therapies in pancreatic cancer 7. Proton&#xD;
      beam therapy may result in lower toxicity, enhanced efficacy and could contribute to improved&#xD;
      local control of patients with LAPC. The capecitabine and oxaliplatin ((CapOx)) regimen&#xD;
      utilized in this trial has been proven to be active in gemcitabine-pretreated patients with&#xD;
      advanced pancreatic cancer.&#xD;
&#xD;
      The current trial will provide important data on the recurrence rates and patterns of failure&#xD;
      using state of the art target agent, chemotherapy and proton beam technology for patients&#xD;
      with LPAC. A median survival of 10 months or greater would be considered evidence of a&#xD;
      regimen potentially worthy of further study as a new treatment paradigm in one arm in a&#xD;
      future phase III trial.&#xD;
&#xD;
      Patients with unresectable or borderline resectable non-metastatic adenocarcinoma of the&#xD;
      pancreas, as defined by 2012 National Comprehensive Cancer Network (NCCN) guidelines, were&#xD;
      included. Patients received neoadjuvant gemcitabine 1000 mg/m2 IV on days 1, 8, 15, 22, 29,&#xD;
      36, and 43 and erlotinib 100 mg by mouth every day for 1-43 days (GE). If there was no&#xD;
      evidence of metastatic disease after GE, then patients preceded with proton therapy to 50.4&#xD;
      Gy in 28 fractions with concurrent capecitabine 825 mg/m2 twice per day (PCT). This was&#xD;
      followed with maintenance oxaliplatin 130 mg/m2 on day 1 and capecitabine 1000 mg/m2 twice&#xD;
      per day on days 2 to 15 (CapOx) for 4 cycles. The primary study objective was 1-year overall&#xD;
      survival (OS). The benchmark was 43% 1-year survival as demonstrated in Radiation Therapy&#xD;
      Oncology Group (RTOG/NRG) 98- 12. The Kaplan-Meier method was used to estimate the one-year&#xD;
      OS and the median OS and progression-free survival (PFS).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Updated chemotherapy regimens currently evaluated in clinical trials due to lack of progress in&#xD;
    treating this condition; analysis continues in the realm of patterns of failure and increasing&#xD;
    quality of life&#xD;
  </why_stopped>
  <start_date type="Actual">January 2, 2013</start_date>
  <completion_date type="Actual">February 19, 2019</completion_date>
  <primary_completion_date type="Actual">February 19, 2019</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>One-year Survival Rate</measure>
    <time_frame>One year after treatment completed.</time_frame>
    <description>Subjects will be followed after treatment completed to determine length of survival rate. The primary study objective was 1-year overall survival (OS, failure: death due to any cause). The Kaplan-Meier method was used to estimate the one-year OS. Secondary Objectives were the frequency of serious adverse events, disease control rate and progression-free survival.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Proton Radiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pre-Proton-chemotherapy (PCT) Patients will receive a combination of the agents (Gemcitabine plus Erlotinib) for 8 weeks prior to PCT Gemcitabine 1000 mg/m2 IV, days 1, 8, 15, 29, 36 and 43 Erlotinib 100 mg po qd days 1-43&#xD;
PCT to be started in 4 to 8 weeks after completion of Pre-PCT Proton therapy: 50.4 Gy/28 fractions (1.8 Gy per fraction) once a day for 5 ½ weeks.&#xD;
Chemotherapy: Capecitabine 825mg/m2 po bid M-F, starting on day 1 of proton therapy until proton therapy completed&#xD;
Post-PCT to be started in 4 to 6 weeks after completion of PCT Oxaliplatin 130 mg/m2, day 1 Capecitabine 1000 mg/m2 po bid on days 2 to 15 for 14 days The CapOx regimen (Capecitabine plus Oxaliplatin) is repeated every 3 weeks for 4 cycles</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Proton, Gemcitabine, Erlotinib, Capecitabine</intervention_name>
    <description>Gemcitabine 1000 mg/m2 iv, days 1, 8, 15, 29, 36 and 43 Erlotinib 100 mg po qd days 1-43 Capecitabine 825mg/m2 po bid M-F, starting on day 1 of proton therapy until proton therapy completed.&#xD;
Post-proton chemotherapy: To be started in 4 to 6 weeks after completion of proton chemotherapy. Oxaliplatin 130 mg/m2 po bid on days 2 to 15 for 14 days. The CapOx regimen (Capcitabine plus Oxaliplatin) is repeated every 3 weeks for 4 cycles.</description>
    <arm_group_label>Proton Radiation</arm_group_label>
  </intervention>
  <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;
          -  Histologically or cytologically confirmed unresectable non-metastatic adenocarcinoma&#xD;
             of the pancreas&#xD;
&#xD;
          -  The American Joint Committee on Cancer (AJCC) stage I-III with unresectable or&#xD;
             borderline unresectable disease as defined by NCCN guidelines&#xD;
&#xD;
          -  Radiological resectability is defined by the following criteria on abdominal imaging:&#xD;
&#xD;
               1. No evidence of tumor extension to the celiac axis, hepatic artery or superior&#xD;
                  mesenteric artery.&#xD;
&#xD;
               2. No evidence of tumor encasement or occlusion of the superior mesenteric vein&#xD;
                  (SMV) or the SMV/portal vein confluence&#xD;
&#xD;
               3. No evidence of visceral or peritoneal metastases&#xD;
&#xD;
          -  Borderline and Unresectable cases would be defined as those that do not meet the&#xD;
             criteria in section and also show no evidence of distant metastatic or intraperitoneal&#xD;
             disease.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status of ≤ 2&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Adequate hematologic reserve, hepatic reserve and renal function&#xD;
&#xD;
          -  White Blood Cell (WBC) &gt; 2,000 cells/mm3&#xD;
&#xD;
          -  Absolute Neutrophil Count (ANC) &gt; 1,500 cells/mm3&#xD;
&#xD;
          -  Platelets &gt; 100,000 cells/mm3&#xD;
&#xD;
          -  Serum bilirubin ≤ 2.5 mg/dL&#xD;
&#xD;
          -  Serum creatinine ≤ 2 x upper limit of normal (ULN), or creatinine clearance (Ccr) ≥&#xD;
             30ml/min&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) &lt; 3 times ULN&#xD;
&#xD;
          -  Aspartate transaminase (AST) &lt; 3 times ULN&#xD;
&#xD;
          -  Albumin &gt; 3.2 g/dl&#xD;
&#xD;
          -  Patient must sign study-specific informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  AJCC stage IV with metastatic disease&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status of &gt; 2&#xD;
&#xD;
          -  Age &lt; 18 years&#xD;
&#xD;
          -  WBC &lt; 2,000 cells/mm3&#xD;
&#xD;
          -  ANC &lt; 1,500 cells/mm3&#xD;
&#xD;
          -  Platelets &gt; 100,000 cells/mm3&#xD;
&#xD;
          -  Serum bilirubin &gt; 2.5 mg/dL&#xD;
&#xD;
          -  Serum creatinine &gt; 2 x upper limit of normal (ULN), or creatinine clearance (Ccr) ≥&#xD;
             30ml/min&#xD;
&#xD;
          -  ALT &gt; 3 times ULN&#xD;
&#xD;
          -  AST &gt; 3 times ULN&#xD;
&#xD;
          -  Albumin &lt; 3.2 g/dl&#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>
  <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>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>February 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <results_first_submitted>June 17, 2021</results_first_submitted>
  <results_first_submitted_qc>August 7, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 10, 2021</results_first_posted>
  <last_update_submitted>August 7, 2021</last_update_submitted>
  <last_update_submitted_qc>August 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2021</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>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Erlotinib Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 27, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/22/NCT01683422/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 16, 2012</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/22/NCT01683422/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Proton Radiation</title>
          <description>Proton, Gemcitabine, Erlotinib, Capecitabine: Gemcitabine 1000 mg/m2 iv, days 1, 8, 15, 29, 36 and 43 Erlotinib 100 mg po qd days 1-43 Capecitabine 825mg/m2 po bid M-F, starting on day 1 of proton therapy until proton therapy completed.&#xD;
Post-proton chemotherapy: To be started in 4 to 6 weeks after completion of proton chemotherapy. Oxaliplatin 130 mg/m2 po bid on days 2 to 15 for 14 days. The CapOx regimen (Capcitabine plus Oxaliplatin) is repeated every 3 weeks for 4 cycles.&#xD;
Proton Radiation</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Proton Radiation</title>
          <description>Radiation: Proton, Gemcitabine, Erlotinib, Capecitabine Gemcitabine 1000 mg/m2 iv, days 1, 8, 15, 29, 36 and 43 Erlotinib 100 mg po qd days 1-43 Capecitabine 825mg/m2 po bid M-F, starting on day 1 of proton therapy until proton therapy completed.&#xD;
Post-proton chemotherapy: To be started in 4 to 6 weeks after completion of proton chemotherapy. Oxaliplatin 130 mg/m2 po bid on days 2 to 15 for 14 days. The CapOx regimen (Capcitabine plus Oxaliplatin) is repeated every 3 weeks for 4 cycles.&#xD;
Radiation: Proton Radiation</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.6" lower_limit="47" upper_limit="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Proton Radiation</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>One-year Survival Rate</title>
        <description>Subjects will be followed after treatment completed to determine length of survival rate. The primary study objective was 1-year overall survival (OS, failure: death due to any cause). The Kaplan-Meier method was used to estimate the one-year OS. Secondary Objectives were the frequency of serious adverse events, disease control rate and progression-free survival.</description>
        <time_frame>One year after treatment completed.</time_frame>
        <population>The study enrolled 9 patients between January 2013 and March 2016, when the trial was closed due to poor accrual.</population>
        <group_list>
          <group group_id="O1">
            <title>Proton Radiation</title>
            <description>Radiation: Proton, Gemcitabine, Erlotinib, Capecitabine Gemcitabine 1000 mg/m2 iv, days 1, 8, 15, 29, 36 and 43 Erlotinib 100 mg po qd days 1-43 Capecitabine 825mg/m2 po bid M-F, starting on day 1 of proton therapy until proton therapy completed.&#xD;
Post-proton chemotherapy: To be started in 4 to 6 weeks after completion of proton chemotherapy. Oxaliplatin 130 mg/m2 po bid on days 2 to 15 for 14 days. The CapOx regimen (Capcitabine plus Oxaliplatin) is repeated every 3 weeks for 4 cycles.&#xD;
Radiation: Proton Radiation</description>
          </group>
        </group_list>
        <measure>
          <title>One-year Survival Rate</title>
          <description>Subjects will be followed after treatment completed to determine length of survival rate. The primary study objective was 1-year overall survival (OS, failure: death due to any cause). The Kaplan-Meier method was used to estimate the one-year OS. Secondary Objectives were the frequency of serious adverse events, disease control rate and progression-free survival.</description>
          <population>The study enrolled 9 patients between January 2013 and March 2016, when the trial was closed due to poor accrual.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.6" lower_limit="31" upper_limit="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>In the RTOG 9812 (NCT00003591) for unresectable pancreatic cancer, a one-year survival rate of 43% was observed. There were 109 analyzable patients on NCT00003591 with 61 still at risk for death at one year. Using the method of Dixon and Simon, a sample size of 39 analyzable patients followed over 12 months will ensure at least 90% probability of detecting a minimum of 17% improvement in the one-year survival rate compared to NCT00003591 at the 0.10 significance level (with a one-sided test).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>The reported p-value was calculated, and is not attempting to indicate the threshold for statistical significance.</non_inferiority_desc>
            <p_value>0.1</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 years</time_frame>
      <desc>Patients with locally advanced pancreatic cancer--9 patients died due to recurrence of disease. Entered as serious Adverse Event (AE)</desc>
      <group_list>
        <group group_id="E1">
          <title>Proton Radiation</title>
          <description>Gemcitabine 1000 mg/m2 iv, days 1, 8, 15, 29, 36 and 43 Erlotinib 100 mg po qd days 1-43 Capecitabine 825mg/m2 po bid M-F, starting on day 1 of proton therapy until proton therapy completed.&#xD;
Post-proton chemotherapy: To be started in 4 to 6 weeks after completion of proton chemotherapy. Oxaliplatin 130 mg/m2 po bid on days 2 to 15 for 14 days. The CapOx regimen (Capcitabine plus Oxaliplatin) is repeated every 3 weeks for 4 cycles.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>serious</sub_title>
                <description>metastatic disease</description>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Gary Yang</name_or_title>
      <organization>Loma Linda University Health</organization>
      <phone>909 558 4000 ext 88056</phone>
      <email>gyang@llu.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01683422
org study id: 5110324
nct id: NCT01683422
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
The current trial will provide important data on the recurrence rates and patterns of failure
      using state of the art target agent, chemotherapy and proton beam technology for patients
      with Locally Advanced Pancreatic Cancer (LAPC). A median survival of 10 months or greater
      would be considered evidence of a regimen potentially worthy of further study as a new
      treatment paradigm in one arm in a future phase III trial.
The current trend toward using the biology of the disease as it becomes evident over a period
      of chemotherapy to better select patients who will benefit from chemoradiotherapy (CRT) seems
      to be the most pragmatic way to proceed, until we have a better means of predicting tumor
      behavior and more active systemic agents. This has led to increased interest in treatment
      regimens incorporating induction chemotherapy with target agent followed by CRT and
      additional chemotherapy for diseases that carry a high risk for systemic relapse.

      The PA.3 trial was the first phase III trial in advanced pancreatic cancer to show a survival
      advantage with the addition of a second drug, in this case the oral Epidermal growth factor
      receptor (EGFR) inhibitor Erlotinib to gemcitabine. The approval provides an important proof
      of concept regarding the use of newer "targeted" therapies in pancreatic cancer 7. Proton
      beam therapy may result in lower toxicity, enhanced efficacy and could contribute to improved
      local control of patients with LAPC. The capecitabine and oxaliplatin ((CapOx)) regimen
      utilized in this trial has been proven to be active in gemcitabine-pretreated patients with
      advanced pancreatic cancer.

      The current trial will provide important data on the recurrence rates and patterns of failure
      using state of the art target agent, chemotherapy and proton beam technology for patients
      with LPAC. A median survival of 10 months or greater would be considered evidence of a
      regimen potentially worthy of further study as a new treatment paradigm in one arm in a
      future phase III trial.

      Patients with unresectable or borderline resectable non-metastatic adenocarcinoma of the
      pancreas, as defined by 2012 National Comprehensive Cancer Network (NCCN) guidelines, were
      included. Patients received neoadjuvant gemcitabine 1000 mg/m2 IV on days 1, 8, 15, 22, 29,
      36, and 43 and erlotinib 100 mg by mouth every day for 1-43 days (GE). If there was no
      evidence of metastatic disease after GE, then patients preceded with proton therapy to 50.4
      Gy in 28 fractions with concurrent capecitabine 825 mg/m2 twice per day (PCT). This was
      followed with maintenance oxaliplatin 130 mg/m2 on day 1 and capecitabine 1000 mg/m2 twice
      per day on days 2 to 15 (CapOx) for 4 cycles. The primary study objective was 1-year overall
      survival (OS). The benchmark was 43% 1-year survival as demonstrated in Radiation Therapy
      Oncology Group (RTOG/NRG) 98- 12. The Kaplan-Meier method was used to estimate the one-year
      OS and the median OS and progression-free survival (PFS).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: One-year Survival Rate
time frame: One year after treatment completed.
description: Subjects will be followed after treatment completed to determine length of survival rate. The primary study objective was 1-year overall survival (OS, failure: death due to any cause). The Kaplan-Meier method was used to estimate the one-year OS. Secondary Objectives were the frequency of serious adverse events, disease control rate and progression-free survival.
arm group label: Proton Radiation
arm group type: Experimental
description: Pre-Proton-chemotherapy (PCT) Patients will receive a combination of the agents (Gemcitabine plus Erlotinib) for 8 weeks prior to PCT Gemcitabine 1000 mg/m2 IV, days 1, 8, 15, 29, 36 and 43 Erlotinib 100 mg po qd days 1-43
PCT to be started in 4 to 8 weeks after completion of Pre-PCT Proton therapy: 50.4 Gy/28 fractions (1.8 Gy per fraction) once a day for 5 ½ weeks.
Chemotherapy: Capecitabine 825mg/m2 po bid M-F, starting on day 1 of proton therapy until proton therapy completed
Post-PCT to be started in 4 to 6 weeks after completion of PCT Oxaliplatin 130 mg/m2, day 1 Capecitabine 1000 mg/m2 po bid on days 2 to 15 for 14 days The CapOx regimen (Capecitabine plus Oxaliplatin) is repeated every 3 weeks for 4 cycles
intervention type: Radiation
intervention name: Proton, Gemcitabine, Erlotinib, Capecitabine
description: Gemcitabine 1000 mg/m2 iv, days 1, 8, 15, 29, 36 and 43 Erlotinib 100 mg po qd days 1-43 Capecitabine 825mg/m2 po bid M-F, starting on day 1 of proton therapy until proton therapy completed.
Post-proton chemotherapy: To be started in 4 to 6 weeks after completion of proton chemotherapy. Oxaliplatin 130 mg/m2 po bid on days 2 to 15 for 14 days. The CapOx regimen (Capcitabine plus Oxaliplatin) is repeated every 3 weeks for 4 cycles.
arm group label: 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
facility: 
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: Pancreatic Neoplasms
mesh term: Gemcitabine
mesh term: Capecitabine
mesh term: Erlotinib Hydrochloride
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 