<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/NCT01728779</url>
  </required_header>
  <id_info>
    <org_study_id>J12137</org_study_id>
    <secondary_id>NA_00069585</secondary_id>
    <nct_id>NCT01728779</nct_id>
  </id_info>
  <brief_title>Stereotactic Body Radiation With Nelfinavir for Oligometastases</brief_title>
  <official_title>Single-Arm Phase II Study of Stereotactic Body Radiation Therapy Concurrent With Nelfinavir for Oligometastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with metastatic lesions of the lung, liver, or bone will be candidates for&#xD;
      treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion&#xD;
      site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral&#xD;
      therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same&#xD;
      Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The use of radiation therapy to treat metastatic tumors is well established and promising&#xD;
      data are emerging with the use of SBRT for metastatic disease. However, the use of a single&#xD;
      large fraction concurrent with a radiosensitizer as is being proposed is not of proven&#xD;
      benefit. This investigation aims to confirm the safety and efficacy for SBRT used&#xD;
      concurrently with a radiosensitizer in the setting of oligometastatic disease. The dose&#xD;
      selected has been chosen with the belief that it is safe and effective based on prior&#xD;
      experience with SBRT of lung cancer, pancreatic cancer and brain radiosurgery. All patients&#xD;
      will be treated with a single fraction (per lesion site), targeted to the lesion concurrently&#xD;
      with the radiosensitizer Nelfinavir.&#xD;
&#xD;
      On the basis of this preclinical evidence, we propose a phase II study of Nelfinavir combined&#xD;
      with SBRT in patients with oligometastatic disease. Because the standard dose of Nelfinavir&#xD;
      for HIV patients is known to be safe and does inhibit the phosphorylation of Akt and decrease&#xD;
      tumor hypoxia, we propose to study this in conjunction with a 15 Gy dose of SBRT. Experience&#xD;
      with single-fraction pulmonary and pancreas SBRT provides a useful dose for this trial. With&#xD;
      published data establishing the relative safety of large single-fraction SBRT to the lungs&#xD;
      and pancreas, we have decided to proceed to determine the safety of 15 Gy SBRT concurrently&#xD;
      with the radiosensitizer Nelfinavir. Once this is established, we propose to continue to&#xD;
      enroll more patients to the study at this dose to determine the efficacy of this type of&#xD;
      therapy.&#xD;
&#xD;
      The proposed study represents an informed estimate based on current knowledge of SBRT doses&#xD;
      and those administered in currently approved image-guided protocols (brain, base of skull,&#xD;
      cervico-thoracic spine, pancreas and liver). This study will refine the current understanding&#xD;
      of single fraction radiation tolerance for normal tissues, thereby making it possible to&#xD;
      treat future patients more safely and aggressively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 8, 2014</start_date>
  <completion_date type="Actual">December 2020</completion_date>
  <primary_completion_date type="Actual">March 2020</primary_completion_date>
  <phase>Phase 2</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>Percentage of Participants With Freedom From Local Progression (FFLP)</measure>
    <time_frame>6 months</time_frame>
    <description>To determine the 6-month Freedom From Local Progression rate (measured as a percentage of participants) in participants treated with radiosensitizer nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction in patients with oligometastatic disease. FFLP is defined as the percent of participants who were free from progression at the 6 month time point.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total Number of Adverse Events Experienced by Participants</measure>
    <time_frame>1 year</time_frame>
    <description>To assess the toxicity of the radiosensitizer Nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction (per lesion site) in patients with oligometastatic disease. Toxicity is assessed by the total number of adverse events based on Common Terminology Criteria for Adverse Events (CTCAE).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Lesions With Local Control at 6 Months Post-treatment</measure>
    <time_frame>6 months</time_frame>
    <description>To determine percent of lesions with local control at 6-months after SBRT delivered to a dose of 15 Gy in 1 fraction (per lesion site) combined with nelfinavir in patients with oligometastatic disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants' Clinical Progress While in Follow-up in Terms of Survival</measure>
    <time_frame>18 months</time_frame>
    <description>To assess the long-term clinical outcomes of this patient population after completion of SBRT in combination with Nelfinavir by determining the percentage of participants with Overall Survival (OS), Freedom From Distant Metastasis (FFDM) and the Progression-Free Survival (PFS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life After Completion of Treatment</measure>
    <time_frame>3 years</time_frame>
    <description>To assess quality of life following completion of SBRT in combination with nelfinavir</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phospho/ Akt Levels With Respect to Lesion Response</measure>
    <time_frame>3 months</time_frame>
    <description>Assess phospho-Akt protein in study participants to determine whether there is a correlation between the level protein and improved lesion response rate.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Oligometastases</condition>
  <arm_group>
    <arm_group_label>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nelfinavir</intervention_name>
    <description>Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.</description>
    <arm_group_label>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</arm_group_label>
    <other_name>Viracept</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic Body Radiation (SBRT)</intervention_name>
    <description>15 Gy dose (per lesion site) of SBRT will be administered</description>
    <arm_group_label>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</arm_group_label>
    <other_name>Stereotactic Body Radiation</other_name>
    <other_name>SBRT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Patient's tumor(s) to be treated is(are) ≤ 5.0 cm or ≤250 cm3&#xD;
&#xD;
          -  Patient must have metastasis at one or more of the following sites: bone, liver, lymph&#xD;
             node and/or lung. No more than five lesions will be treated.&#xD;
&#xD;
          -  Histological confirmation of malignancy (primary or metastatic tumor).&#xD;
&#xD;
          -  Patient may have any prior therapy allowed aside from having had prior radiotherapy to&#xD;
             the treatment site (see exclusion criteria 5.2.3).&#xD;
&#xD;
          -  Patient must be ≥ 18 years of age.&#xD;
&#xD;
          -  Patient must have a life expectancy ≥ 9 months.&#xD;
&#xD;
          -  Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.&#xD;
&#xD;
          -  Patient must have normal organ and marrow function.&#xD;
&#xD;
          -  Patient must have the ability to understand and the willingness to sign a written&#xD;
             informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering&#xD;
             the study&#xD;
&#xD;
          -  Patients receiving any other investigational agents&#xD;
&#xD;
          -  Patient who has had any prior radiotherapy to the treatment site(s)&#xD;
&#xD;
          -  Patients taking drugs that are contraindicated with nelfinavir, including any of the&#xD;
             following:&#xD;
&#xD;
        Amiodarone, Quinidine, Rifampin, Dihydroergotamine, Ergonovine, Ergotamine,&#xD;
        Methylergonovine, Hypericum perforatum (St. John's wort), Lovastatin, Simvastatin,&#xD;
        Pimozide, Midazolam, Triazolam&#xD;
&#xD;
          -  Women of child bearing potential who refuse to take a pregnancy test prior to&#xD;
             treatment&#xD;
&#xD;
          -  Participation in another concurrent treatment protocol while being treated on this&#xD;
             protocol and through to 3 months after treatment on this protocol has ended&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Inability to understand the informed consent document&#xD;
&#xD;
          -  Inability to sign the informed consent document&#xD;
&#xD;
          -  Poor liver function suggestive of cirrhosis or steatohepatitis&#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>Phuoc Tran, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>October 12, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <results_first_submitted>March 26, 2021</results_first_submitted>
  <results_first_submitted_qc>March 26, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">April 23, 2021</results_first_posted>
  <last_update_submitted>June 14, 2021</last_update_submitted>
  <last_update_submitted_qc>June 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nelfinavir</mesh_term>
  </intervention_browse>
  <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>May 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT01728779/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 38 patients were accrued between January 2014 and December 2015 with one who withdrew consent and 37 were included in the analysis.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</title>
          <description>Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.&#xD;
Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.&#xD;
Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>38 patients were enrolled but one patient withdrew consent. The analysis included a total of 37 patients.</population>
      <group_list>
        <group group_id="B1">
          <title>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</title>
          <description>Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.&#xD;
Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.&#xD;
Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="37"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65" lower_limit="35" 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="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Freedom From Local Progression (FFLP)</title>
        <description>To determine the 6-month Freedom From Local Progression rate (measured as a percentage of participants) in participants treated with radiosensitizer nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction in patients with oligometastatic disease. FFLP is defined as the percent of participants who were free from progression at the 6 month time point.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</title>
            <description>Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.&#xD;
Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.&#xD;
Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Freedom From Local Progression (FFLP)</title>
          <description>To determine the 6-month Freedom From Local Progression rate (measured as a percentage of participants) in participants treated with radiosensitizer nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction in patients with oligometastatic disease. FFLP is defined as the percent of participants who were free from progression at the 6 month time point.</description>
          <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="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.4" lower_limit="61.4" upper_limit="88.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of Adverse Events Experienced by Participants</title>
        <description>To assess the toxicity of the radiosensitizer Nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction (per lesion site) in patients with oligometastatic disease. Toxicity is assessed by the total number of adverse events based on Common Terminology Criteria for Adverse Events (CTCAE).</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</title>
            <description>Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.&#xD;
Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.&#xD;
Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Adverse Events Experienced by Participants</title>
          <description>To assess the toxicity of the radiosensitizer Nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction (per lesion site) in patients with oligometastatic disease. Toxicity is assessed by the total number of adverse events based on Common Terminology Criteria for Adverse Events (CTCAE).</description>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anorexia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cough</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Agitation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine Amino Trans increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline Phosphatase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alopecia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT Increase</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Apnea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate Amino Trans increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ataxia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bloating</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bronchial Infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bruising</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chills</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Colonic obstruction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Concentration Impairment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Conjunctivitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Constipation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cytokine Release Syndrome</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dehydration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depression</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dermatitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dry Mouth</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspepsia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspnea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Edema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Esophageal pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Esophagitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fecal Incontinence</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fever</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastritis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Headache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hearing Loss</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hematuria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemaglobin Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemorrhoids</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hiccups</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hot Flashes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperglycemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperkalemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypernatremia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypertension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoglycemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypokalemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyponatremia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoxia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Insomnia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte absolute decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Malaise</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neuralgia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White blood cells decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weight Loss</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weight Gain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vomitting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urticaria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urinary Incontinence</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urinary Frequency</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tremor</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Toothache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stomatitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stomach Pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Oral mucositis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Perineal Pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Periodontal Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Proctitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pruritis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Radiation Recall Rctn</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin Infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Short term memory impairment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Lesions With Local Control at 6 Months Post-treatment</title>
        <description>To determine percent of lesions with local control at 6-months after SBRT delivered to a dose of 15 Gy in 1 fraction (per lesion site) combined with nelfinavir in patients with oligometastatic disease.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</title>
            <description>Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.&#xD;
Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.&#xD;
Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Lesions With Local Control at 6 Months Post-treatment</title>
          <description>To determine percent of lesions with local control at 6-months after SBRT delivered to a dose of 15 Gy in 1 fraction (per lesion site) combined with nelfinavir in patients with oligometastatic disease.</description>
          <units>percentage of lesions</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <units_analyzed>Lesions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Lesions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.5" lower_limit="64.5" upper_limit="84.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants' Clinical Progress While in Follow-up in Terms of Survival</title>
        <description>To assess the long-term clinical outcomes of this patient population after completion of SBRT in combination with Nelfinavir by determining the percentage of participants with Overall Survival (OS), Freedom From Distant Metastasis (FFDM) and the Progression-Free Survival (PFS).</description>
        <time_frame>18 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</title>
            <description>Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.&#xD;
Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.&#xD;
Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered</description>
          </group>
        </group_list>
        <measure>
          <title>Participants' Clinical Progress While in Follow-up in Terms of Survival</title>
          <description>To assess the long-term clinical outcomes of this patient population after completion of SBRT in combination with Nelfinavir by determining the percentage of participants with Overall Survival (OS), Freedom From Distant Metastasis (FFDM) and the Progression-Free Survival (PFS).</description>
          <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="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall Survival</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.7" lower_limit="73.8" upper_limit="96.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Freedom From Distant Metastasis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.4" lower_limit="43.9" upper_limit="76.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progression-Free Survival</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.6" lower_limit="39.7" upper_limit="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Quality of Life After Completion of Treatment</title>
        <description>To assess quality of life following completion of SBRT in combination with nelfinavir</description>
        <time_frame>3 years</time_frame>
        <population>Data was not collected for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</title>
            <description>Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.&#xD;
Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.&#xD;
Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered</description>
          </group>
        </group_list>
        <measure>
          <title>Quality of Life After Completion of Treatment</title>
          <description>To assess quality of life following completion of SBRT in combination with nelfinavir</description>
          <population>Data was not collected for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phospho/ Akt Levels With Respect to Lesion Response</title>
        <description>Assess phospho-Akt protein in study participants to determine whether there is a correlation between the level protein and improved lesion response rate.</description>
        <time_frame>3 months</time_frame>
        <population>Data was not collected for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</title>
            <description>Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.&#xD;
Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.&#xD;
Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered</description>
          </group>
        </group_list>
        <measure>
          <title>Phospho/ Akt Levels With Respect to Lesion Response</title>
          <description>Assess phospho-Akt protein in study participants to determine whether there is a correlation between the level protein and improved lesion response rate.</description>
          <population>Data was not collected for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 36 months.</time_frame>
      <desc>All AEs were recorded throughout the study, however there were only 5 grade 3 adverse events in three patients as defined by CTCAE.</desc>
      <group_list>
        <group group_id="E1">
          <title>Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)</title>
          <description>Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.&#xD;
Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.&#xD;
Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (Unspecified)</default_vocab>
        <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="3" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Weight Loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="37" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="22" subjects_affected="22" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Lymphocyte Absolute Increase</sub_title>
                <counts group_id="E1" events="37" subjects_affected="37" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>WBC Decrease</sub_title>
                <counts group_id="E1" events="22" subjects_affected="22" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Platelet Count Decrease</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hot Flashes</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="32" subjects_affected="32" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="18" subjects_affected="18" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="36" subjects_affected="36" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Fecal Incontinence</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Hemmorhoids</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="22" subjects_affected="22" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Vomitting</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Dyspenea</sub_title>
                <counts group_id="E1" events="25" subjects_affected="25" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Edema</sub_title>
                <counts group_id="E1" events="21" subjects_affected="21" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="37" subjects_affected="37" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Weight Loss</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Weight Increase</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Stomach Pain</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Pruritis</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Concentration impairment</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="19" subjects_affected="19" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="16" subjects_affected="16" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Bilirubin</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Urinary Incontinence</sub_title>
                <counts group_id="E1" events="25" subjects_affected="25" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>cough</sub_title>
                <counts group_id="E1" events="24" subjects_affected="24" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Esophogitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Dana Kaplin</name_or_title>
      <organization>Johns Hopkins University</organization>
      <phone>410-614-3950</phone>
      <email>dkaplin1@jhmi.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/NCT01728779
org study id: J12137
secondary id: NA_00069585
nct id: NCT01728779
lead sponsor: 
has dmc: Yes
Patients with metastatic lesions of the lung, liver, or bone will be candidates for
      treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion
      site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral
      therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same
      Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.
The use of radiation therapy to treat metastatic tumors is well established and promising
      data are emerging with the use of SBRT for metastatic disease. However, the use of a single
      large fraction concurrent with a radiosensitizer as is being proposed is not of proven
      benefit. This investigation aims to confirm the safety and efficacy for SBRT used
      concurrently with a radiosensitizer in the setting of oligometastatic disease. The dose
      selected has been chosen with the belief that it is safe and effective based on prior
      experience with SBRT of lung cancer, pancreatic cancer and brain radiosurgery. All patients
      will be treated with a single fraction (per lesion site), targeted to the lesion concurrently
      with the radiosensitizer Nelfinavir.

      On the basis of this preclinical evidence, we propose a phase II study of Nelfinavir combined
      with SBRT in patients with oligometastatic disease. Because the standard dose of Nelfinavir
      for HIV patients is known to be safe and does inhibit the phosphorylation of Akt and decrease
      tumor hypoxia, we propose to study this in conjunction with a 15 Gy dose of SBRT. Experience
      with single-fraction pulmonary and pancreas SBRT provides a useful dose for this trial. With
      published data establishing the relative safety of large single-fraction SBRT to the lungs
      and pancreas, we have decided to proceed to determine the safety of 15 Gy SBRT concurrently
      with the radiosensitizer Nelfinavir. Once this is established, we propose to continue to
      enroll more patients to the study at this dose to determine the efficacy of this type of
      therapy.

      The proposed study represents an informed estimate based on current knowledge of SBRT doses
      and those administered in currently approved image-guided protocols (brain, base of skull,
      cervico-thoracic spine, pancreas and liver). This study will refine the current understanding
      of single fraction radiation tolerance for normal tissues, thereby making it possible to
      treat future patients more safely and aggressively.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Freedom From Local Progression (FFLP)
time frame: 6 months
description: To determine the 6-month Freedom From Local Progression rate (measured as a percentage of participants) in participants treated with radiosensitizer nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction in patients with oligometastatic disease. FFLP is defined as the percent of participants who were free from progression at the 6 month time point.
measure: Total Number of Adverse Events Experienced by Participants
time frame: 1 year
description: To assess the toxicity of the radiosensitizer Nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction (per lesion site) in patients with oligometastatic disease. Toxicity is assessed by the total number of adverse events based on Common Terminology Criteria for Adverse Events (CTCAE).
measure: Percent of Lesions With Local Control at 6 Months Post-treatment
time frame: 6 months
description: To determine percent of lesions with local control at 6-months after SBRT delivered to a dose of 15 Gy in 1 fraction (per lesion site) combined with nelfinavir in patients with oligometastatic disease.
measure: Participants' Clinical Progress While in Follow-up in Terms of Survival
time frame: 18 months
description: To assess the long-term clinical outcomes of this patient population after completion of SBRT in combination with Nelfinavir by determining the percentage of participants with Overall Survival (OS), Freedom From Distant Metastasis (FFDM) and the Progression-Free Survival (PFS).
measure: Quality of Life After Completion of Treatment
time frame: 3 years
description: To assess quality of life following completion of SBRT in combination with nelfinavir
measure: Phospho/ Akt Levels With Respect to Lesion Response
time frame: 3 months
description: Assess phospho-Akt protein in study participants to determine whether there is a correlation between the level protein and improved lesion response rate.
arm group label: Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
arm group type: Experimental
description: Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.
intervention type: Drug
intervention name: Nelfinavir
description: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.
arm group label: Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
other name: Viracept
intervention type: Radiation
intervention name: Stereotactic Body Radiation (SBRT)
description: 15 Gy dose (per lesion site) of SBRT will be administered
arm group label: Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
other name: Stereotactic Body Radiation
other name: SBRT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Phuoc Tran, M.D.
role: Principal Investigator
affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
facility: 
country: United States
responsible party type: Sponsor
mesh term: Nelfinavir
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 