<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/NCT01671488</url>
  </required_header>
  <id_info>
    <org_study_id>BrUOG 276</org_study_id>
    <nct_id>NCT01671488</nct_id>
  </id_info>
  <brief_title>A Phase I/II Evaluation of ADXS11-001, Mitomycin, 5-fluorouracil (5-FU) and IMRT for Anal Cancer</brief_title>
  <acronym>276</acronym>
  <official_title>BrUOG 276: A Phase I/II Evaluation of ADXS11-001, Mitomycin,5-fluorouracil (5-FU) and IMRT for Anal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brown University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rhode Island Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Miriam Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Brown University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to study the safety and effectiveness of ADXS11-001 when&#xD;
      combined with standard chemotherapy and radiation treatment for anal cancer. ADXS11-001 is an&#xD;
      investigational agent that is not approved by the FDA to treat anal cancer or any other&#xD;
      cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Novel treatments are needed in anal cancer. An important percentage of patients with locally&#xD;
      advanced anal cancer will have persistent loco-regional disease or develop systemic&#xD;
      metastases. Virtually all cases of anal cancer are related to infection by HPV. Anal cancer&#xD;
      cells infected with HPV have the tumor associated antigen HPV E7. ADXS11-001 causes antigen&#xD;
      presenting cells to be stimulated to facilitate immune cells to attack cancer cells&#xD;
      expressing HPV E7. ADXS11-001, at the phase II dose of 1x109 CFU, has been shown to be safe&#xD;
      in patients with advanced cervical cancer which also is caused by HPV infection. Anti-tumor&#xD;
      activity and safety have been demonstrated in cervical cancer to single agent ADXS11-001 and&#xD;
      the combination of ADXS11-001 and cisplatin chemotherapy. Data presented at ASCO 2012&#xD;
      ADXS11-001 is currently being evaluated in women in the United States with cervical&#xD;
      intraepithelial neoplasia. Radiation may augment the activity of ADXS11-001 increasing the&#xD;
      exposure of tumor related antigens thereby increasing the chance for loco-regional disease&#xD;
      eradication and preventing systemic recurrence. Therefore, ADXS11-001 may increase complete&#xD;
      response, prevent recurrence disease and increase disease-free and overall survival in anal&#xD;
      cancer. This protocol will develop sufficient preliminary safety and efficacy data to&#xD;
      facilitate the investigation of ADXS11-001 in anal cancer within &quot;NRG&quot;, the newly formed&#xD;
      cooperative group based on the merger of the RTOG, NSABP and GOG.&#xD;
&#xD;
      As described above, Phase I studies and preliminary data from phase II studies have&#xD;
      demonstrated that ADXS11-001, 1x109 CFU, can be safely administered as a single agent and in&#xD;
      combination with chemotherapy. For example in over 200 patients treated at the dose of&#xD;
      1x109CFU there have been no cases of severe listeria bacteremia or grade 3 cardiopulmonary&#xD;
      toxicity. However, since ADXS11-001 has not previously been administered with radiation, the&#xD;
      primary objective of this study will be to establish the safety of the addition of ADXS11-001&#xD;
      to chemoradiation for anal cancer. The following schedules will be assessed.&#xD;
&#xD;
      • Treatment Schedule: The first dose will be given 10-14 days prior to the initiation of&#xD;
      chemoradiation. The 2nd-4th dosages of ADXS11-001will not be until after completion of all&#xD;
      chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of&#xD;
      10 days after completion of chemoradiation, ANC &gt; 1,000 cells/mm3, serum creatinine &lt; 1.5&#xD;
      mg/dl and all toxicities from chemoradiation have resolved to grade 2 or less. The subsequent&#xD;
      third and fourth treatment with of ADXS11 will be administered at 28 day intervals. This will&#xD;
      provide the needed safety data to evaluate Treatment Schedule #2.&#xD;
&#xD;
      Standard treatment with mitomycin, 5-FU and radiation for anal cancer has substantial&#xD;
      toxicity. In RTOG 9811, 74% of patients had grade 3/4 nonhematologic toxicity and 61% of&#xD;
      patients had grade 3 or grade 4 hematologic toxicity from this regimen. Therefore, the&#xD;
      toxicities of standard chemoradiation with mitomycin, 5-FU and radiation are well above the&#xD;
      conventionally accepted parameters in a phase I study even prior to adding ADXS11-001.&#xD;
      However, it is critical that the addition of ADXS-11-001 does not compromise the delivery of&#xD;
      potentially curative standard chemoradiation for anal cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    pilot data to be used for upcoming larger trial.&#xD;
  </why_stopped>
  <start_date type="Actual">February 2013</start_date>
  <completion_date type="Actual">February 2018</completion_date>
  <primary_completion_date type="Actual">February 2018</primary_completion_date>
  <phase>Phase 1/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>To Evaluate the Safety of the Addition of ADXS11-001 to Standard Chemoradiation for Patients With Anal Cancer.</measure>
    <time_frame>Baseline, then prior to each ADXS11-001 and weekly during radiation. Assessments 1-2 weeks post radiation then 2-6 weeks post vaccine and off study and 30 days post treatment.</time_frame>
    <description>Evaluate maximal toxicities via CTCAE version 4.0 All adverse events, serious and non-serious, were captured from date of ICF through 4 weeks post treatment completion- regardless of causality.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To Evaluate the 6-month Clinical Complete Response Rate for Patients With Anal Cancer Treated With ADXS11-001 Mitomycin, 5-FU and IMRT.</measure>
    <time_frame>Tumor evaluation 6 months after coming off study</time_frame>
    <description>Patients to undergo tumor evaluation assessment (via sigmoidoscopy, proctoscopy, colonoscopy or anoscope) 6 months post the start of chemotherapy/radiation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To Evaluate Progression-free and Overall Survival for Patients With Anal Cancer Treated With ADXS11-001, Mitomycin, 5-FU and IMRT.</measure>
    <time_frame>Follow up and survival status at 6 months and 1 year post coming off study and annually until patient has been off for 5 years</time_frame>
    <description>Patients terminating study treatment early prior to disease recurrence will be followed every 6 months for year 1 then annually for a total of 5 years. The follow-up portion will commence once patient comes off study or post the 2-6 week post the 4th treatment time point/visit.&#xD;
Assessments were tumor evaluation via sigmoidoscopy, proctoscopy, colonoscopy or anoscope and also chest/abdomen/pelvic imaging.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Anal Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The first dose will be given 10-14 days prior to the initiation of chemoradiation.&#xD;
Patient will then receive 5-FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days and Mitomycin: 10 mg/m2, day 1 and 29 with IMRT radiation: 54 Gy in 30 fractions at 1.8 Gy per fraction.&#xD;
The 2-4th dosages of ADXS11-001 will not be until after completion of all chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of 10 days after completion of chemoradiation. The subsequent third and fourth treatment with of ADXS11 will be administered at 28 day intervals.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Treatment</intervention_name>
    <description>ADXS11-001 will be given at a dose of 1x109 cfu intravenously once every 28 days for 4 total doses. All 4 doses of ADXS11-001 will be 1x109 cfu.</description>
    <arm_group_label>Treatment</arm_group_label>
    <other_name>ADXS11-001</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5FU</intervention_name>
    <description>1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mitomycin</intervention_name>
    <description>10 mg/m2, day 1 and 29 (day 29 can be + 7 days)</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>IMRT</intervention_name>
    <description>54 Gy in 30 fractions at 1.8 Gy per fraction.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        3.1.1 Histologically-proven, invasive primary squamous, basaloid, or cloacogenic carcinoma&#xD;
        of the anal canal; 3.1.2 AJCC 2009 TN Stage: T1N1-N3, T2(&lt; 4cm)N1-N3, T2(&gt; 4cm)N0,T3N0-3,&#xD;
        T4N0-3;based upon the following minimum diagnostic workup: 3.1.2.1 History/physical&#xD;
        examination within 14 days prior to registration; 3.1.2.2 Within 42 days prior to&#xD;
        registration, the patient must have an anal examination by any of the following:&#xD;
        colonoscopy, sigmoidoscopy, or rigid proctoscopy, with documentation of primary anal lesion&#xD;
        size, distance from anal verge.&#xD;
&#xD;
        3.1.3 Groin examination within 42 days prior to registration with documentation of any&#xD;
        groin adenopathy and lymphadenopathy (location: right vs. left; medial vs. lateral; mobile&#xD;
        vs. fixed; and size); 3.1.4 X-ray (PA and lateral), CT scan, or PET/CT scan of the chest&#xD;
        within 42 days prior to registration; 3.1.5 CT scan, MRI, or PET/CT of the abdomen and&#xD;
        pelvis within 42 days prior to registration; 3.1.6 Zubrod Performance Status 0-1; 3.1.7 Age&#xD;
        ≥ 18; 3.1.8 Laboratory data obtained ≤ 14 days prior to registration on study, with&#xD;
        adequate bone marrow, hepatic and renal function defined as follows:&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;&#xD;
&#xD;
          -  Platelets ≥ 100,000 cells/mm3;&#xD;
&#xD;
          -  Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve&#xD;
             Hgb ≥ 8.0 g/dl is acceptable.);&#xD;
&#xD;
          -  Serum creatinine ≤ 1.5 mg/dl;&#xD;
&#xD;
          -  Bilirubin &lt; 1.4mg/dl;&#xD;
&#xD;
          -  ALT/AST &lt; 3 x ULN;&#xD;
&#xD;
          -  Negative serum pregnancy test for women of child-bearing potential; 3.1.9 Women of&#xD;
             childbearing potential and male participants must agree to use a 2 forms of medically&#xD;
             effective means of birth control (such as a condom and spermicide) throughout their&#xD;
             participation in the treatment phase of the study and for 90 days post last dose of&#xD;
             study drug.&#xD;
&#xD;
        3.1.10 Patients must sign a study-specific informed consent prior to study entry.&#xD;
&#xD;
        3.1.11 Patients with a history of clinically significant pulmonary disease must have PFTs&#xD;
        demonstrating a DLCO ≥ 40%. This testing is considered standard of care prior to mitomycin,&#xD;
        5-FU and radiation.&#xD;
&#xD;
        3.1.12 Patients with a history of clinically significant cardiac disease must have a LVEF ≥&#xD;
        30% by ECHO. (MUGA scan may also be used to determine LVEF) This testing is considered&#xD;
        standard of care prior to mitomycin, 5-FU and radiation.&#xD;
&#xD;
        3.1.13 Patients must be able to swallow pills.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        3.2.1 Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free&#xD;
        for a minimum of 2 years; 3.2.2 Prior systemic chemotherapy for anal cancer; 3.2.3 Prior&#xD;
        allergic reaction to the study drugs involved in this protocol. 3.2.4 Prior radiotherapy to&#xD;
        the pelvis that would result in overlap of radiation therapy fields; 3.2.5 Severe, active&#xD;
        co-morbidity, defined as follows: 3.2.5.1 Patients with uncontrolled intercurrent illness&#xD;
        including, but not limited to ongoing or active infection, symptomatic congestive heart&#xD;
        failure, unstable angina pectoris and cardiac arrhythmia are ineligible. Furthermore,&#xD;
        patients with unstable angina and/or congestive heart failure requiring hospitalization&#xD;
        within the past 6 months are ineligible; 3.2.5.2 Patients with active infection requiring&#xD;
        systemic therapy (oral or IV) or those currently receiving antibiotics that cannot&#xD;
        discontinue prior to dosing are ineligible.&#xD;
&#xD;
        3.2.5.3 Transmural myocardial infarction within the last 6 months; 3.2.5.4 Acute bacterial&#xD;
        or fungal infection requiring intravenous antibiotics at the time of registration; 3.2.5.5&#xD;
        Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring&#xD;
        hospitalization or precluding study therapy at the time of registration; 3.2.5.6 Hepatic&#xD;
        insufficiency resulting in clinical jaundice and/or coagulation defects; 3.2.6 Patients&#xD;
        known to be seropositive for HIV and/or active hepatitis, even if liver function studies&#xD;
        are in the eligible range.&#xD;
&#xD;
        3.2.7 Other immunocompromised status (e.g., organ transplant or chronic glucocorticoid&#xD;
        use).If patient has diagnosis of immunodeficiency, is dependent on or has received systemic&#xD;
        steroids therapy or any form of immunosuppressive therapy within 7 days prior to the first&#xD;
        dose of ADXS11-001 they are ineligible. Topical corticosteroid or occasional inhaled&#xD;
        corticosteroids are allowed.&#xD;
&#xD;
        3.2.8 Women who are pregnant or lactating are ineligible because the treatment involved in&#xD;
        this study may be significantly teratogenic and there is the potential for transmission of&#xD;
        listeria to the infant.&#xD;
&#xD;
        3.2.9 Patients allergic to or with a sensitivity to penicillin, ampicillin,&#xD;
        trimethoprim-sulfa and quinolones (including history of rash or anaphylaxis).&#xD;
&#xD;
        3.2.10 Patients allergic to naproxen. 3.2.11 Patients receiving oral or IV antibiotics&#xD;
        3.2.12 Patients with a prior history of a splenectomy and/or sickle cell trait/disease&#xD;
        3.2.13 Patient has implanted medical device(s) that pose a high risk for colonization&#xD;
        and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves,&#xD;
        pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous&#xD;
        implant(s)). NOTE: More common devices and prosthetics which include arterial and venous&#xD;
        stents, dental and breast implants and venous access devices (e.g. Port-a-Cath or Mediport)&#xD;
        are permitted. Sponsor must be contacted prior to consenting any subject who has any other&#xD;
        device and/or implant. Site is required to submit to BrUOG ALL surgical implants patient&#xD;
        has ever had in their medical history and ALL surgeries regardless of link to this cancer&#xD;
        diagnosis.&#xD;
&#xD;
        3.2.14 Patients who are receiving or may receive future treatment with PI3K or TNFα&#xD;
        inhibitors. To be confirmed by treating medical oncologist in writing 3.2.15 Has undergone&#xD;
        a major surgery, including surgery for a new artificial implant and/or device, within 6&#xD;
        weeks prior to the initiation of ADXS11-001 treatment. NOTE: if patient underwent surgery &gt;&#xD;
        6 weeks from start of ADSX11-001, all toxicities and/or complications must have recovered&#xD;
        to baseline or Grade 1 prior to the initiation of ADXS11-001 study therapy.&#xD;
&#xD;
        3.2.16 Patient not being willing to have new infusion line placed for each infusion of&#xD;
        ADXS11-001 as existing or newly placed central venous catheter or infusion ports are not&#xD;
        allowed to be used for ADXS11-001 administration. Must be confirmed as discussed with&#xD;
        patient and that they agreed.&#xD;
&#xD;
        3.2.17 Patient not willing to comply with requirement of central venous catheter or&#xD;
        infusion port must not be used for 72 hours following the completion of the ADXS11-001&#xD;
        infusion and the patient receives the first post-treatment dose of oral antibiotics. Must&#xD;
        be confirmed as discussed with patient and that they agreed.&#xD;
&#xD;
        3.2.18 Live vaccines within 30 days prior to the first dose of trial treatment and while&#xD;
        participating in the trial. Examples of live vaccines include, but are not limited to, the&#xD;
        following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid&#xD;
        (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus&#xD;
        vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live&#xD;
        attenuated vaccines and are not allowed. All recent vaccines (within 30 days) to be listed&#xD;
        on conmed log 3.2.19 Patient has a history of listeriosis or prior ADXS11-001 therapy.&#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>Howard Safran, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brown University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Miriam Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02906</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 23, 2012</study_first_posted>
  <results_first_submitted>December 13, 2016</results_first_submitted>
  <results_first_submitted_qc>April 4, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 12, 2017</results_first_posted>
  <last_update_submitted>February 13, 2020</last_update_submitted>
  <last_update_submitted_qc>February 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brown University</investigator_affiliation>
    <investigator_full_name>howard safran</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Anal Cancer</keyword>
  <keyword>Mitomycin</keyword>
  <keyword>5-Fluorouracil</keyword>
  <keyword>5-FU</keyword>
  <keyword>IMRT</keyword>
  <keyword>ADXS11-001</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anus Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mitomycins</mesh_term>
    <mesh_term>Mitomycin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 28, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT01671488/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment</title>
          <description>The first dose will be given 10-14 days prior to the initiation of chemoradiation.&#xD;
Patient will then receive 5-FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days and Mitomycin: 10 mg/m2, day 1 and 29 with IMRT radiation: 54 Gy in 30 fractions at 1.8 Gy per fraction.&#xD;
The 2-4th dosages of ADXS11-001 will not be until after completion of all chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of 10 days after completion of chemoradiation. The subsequent third and fourth treatment with of ADXS11 will be administered at 28 day intervals.&#xD;
Treatment: ADXS11-001 will be given at a dose of 1x109 cfu intravenously once every 28 days for 4 total doses. All 4 doses of ADXS11-001 will be 1x109 cfu.&#xD;
5FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days&#xD;
Mitomycin: 10 mg/m2, day 1 and 29 (day 29 can be + 7 days)&#xD;
IMRT: 54 Gy in 30 fractions at 1.8 Gy per fraction.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </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>
      <group_list>
        <group group_id="B1">
          <title>Treatment</title>
          <description>The first dose will be given 10-14 days prior to the initiation of chemoradiation.&#xD;
Patient will then receive 5-FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days and Mitomycin: 10 mg/m2, day 1 and 29 with IMRT radiation: 54 Gy in 30 fractions at 1.8 Gy per fraction.&#xD;
The 2-4th dosages of ADXS11-001 will not be until after completion of all chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of 10 days after completion of chemoradiation. The subsequent third and fourth treatment with of ADXS11 will be administered at 28 day intervals.&#xD;
Treatment: ADXS11-001 will be given at a dose of 1x109 cfu intravenously once every 28 days for 4 total doses. All 4 doses of ADXS11-001 will be 1x109 cfu.&#xD;
5FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days&#xD;
Mitomycin: 10 mg/m2, day 1 and 29 (day 29 can be + 7 days)&#xD;
IMRT: 54 Gy in 30 fractions at 1.8 Gy per fraction.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="60.36" lower_limit="37" upper_limit="71"/>
                  </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="6"/>
                  </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>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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </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>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>To Evaluate the Safety of the Addition of ADXS11-001 to Standard Chemoradiation for Patients With Anal Cancer.</title>
        <description>Evaluate maximal toxicities via CTCAE version 4.0 All adverse events, serious and non-serious, were captured from date of ICF through 4 weeks post treatment completion- regardless of causality.</description>
        <time_frame>Baseline, then prior to each ADXS11-001 and weekly during radiation. Assessments 1-2 weeks post radiation then 2-6 weeks post vaccine and off study and 30 days post treatment.</time_frame>
        <population>Patient's who received treatment on study</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment</title>
            <description>The first dose will be given 10-14 days prior to the initiation of chemoradiation.&#xD;
Patient will then receive 5-FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days and Mitomycin: 10 mg/m2, day 1 and 29 with IMRT radiation: 54 Gy in 30 fractions at 1.8 Gy per fraction.&#xD;
The 2-4th dosages of ADXS11-001 will not be until after completion of all chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of 10 days after completion of chemoradiation. The subsequent third and fourth treatment with of ADXS11 will be administered at 28 day intervals.&#xD;
Treatment: ADXS11-001 will be given at a dose of 1x109 cfu intravenously once every 28 days for 4 total doses. All 4 doses of ADXS11-001 will be 1x109 cfu.&#xD;
5FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days&#xD;
Mitomycin: 10 mg/m2, day 1 and 29 (day 29 can be + 7 days)&#xD;
IMRT: 54 Gy in 30 fractions at 1.8 Gy per fraction.</description>
          </group>
        </group_list>
        <measure>
          <title>To Evaluate the Safety of the Addition of ADXS11-001 to Standard Chemoradiation for Patients With Anal Cancer.</title>
          <description>Evaluate maximal toxicities via CTCAE version 4.0 All adverse events, serious and non-serious, were captured from date of ICF through 4 weeks post treatment completion- regardless of causality.</description>
          <population>Patient's who received treatment on study</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>To Evaluate the 6-month Clinical Complete Response Rate for Patients With Anal Cancer Treated With ADXS11-001 Mitomycin, 5-FU and IMRT.</title>
        <description>Patients to undergo tumor evaluation assessment (via sigmoidoscopy, proctoscopy, colonoscopy or anoscope) 6 months post the start of chemotherapy/radiation.</description>
        <time_frame>Tumor evaluation 6 months after coming off study</time_frame>
        <population>Number of patient's who received treatment on study</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment</title>
            <description>The first dose will be given 10-14 days prior to the initiation of chemoradiation.&#xD;
Patient will then receive 5-FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days and Mitomycin: 10 mg/m2, day 1 and 29 with IMRT radiation: 54 Gy in 30 fractions at 1.8 Gy per fraction.&#xD;
The 2-4th dosages of ADXS11-001 will not be until after completion of all chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of 10 days after completion of chemoradiation. The subsequent third and fourth treatment with of ADXS11 will be administered at 28 day intervals.&#xD;
Treatment: ADXS11-001 will be given at a dose of 1x109 cfu intravenously once every 28 days for 4 total doses. All 4 doses of ADXS11-001 will be 1x109 cfu.&#xD;
5FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days&#xD;
Mitomycin: 10 mg/m2, day 1 and 29 (day 29 can be + 7 days)&#xD;
IMRT: 54 Gy in 30 fractions at 1.8 Gy per fraction.</description>
          </group>
        </group_list>
        <measure>
          <title>To Evaluate the 6-month Clinical Complete Response Rate for Patients With Anal Cancer Treated With ADXS11-001 Mitomycin, 5-FU and IMRT.</title>
          <description>Patients to undergo tumor evaluation assessment (via sigmoidoscopy, proctoscopy, colonoscopy or anoscope) 6 months post the start of chemotherapy/radiation.</description>
          <population>Number of patient's who received treatment on study</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>To Evaluate Progression-free and Overall Survival for Patients With Anal Cancer Treated With ADXS11-001, Mitomycin, 5-FU and IMRT.</title>
        <description>Patients terminating study treatment early prior to disease recurrence will be followed every 6 months for year 1 then annually for a total of 5 years. The follow-up portion will commence once patient comes off study or post the 2-6 week post the 4th treatment time point/visit.&#xD;
Assessments were tumor evaluation via sigmoidoscopy, proctoscopy, colonoscopy or anoscope and also chest/abdomen/pelvic imaging.</description>
        <time_frame>Follow up and survival status at 6 months and 1 year post coming off study and annually until patient has been off for 5 years</time_frame>
        <population>As one patient expired prior to 6 month assessment, the total n used was 9 to assess PFS</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment</title>
            <description>The first dose will be given 10-14 days prior to the initiation of chemoradiation.&#xD;
Patient will then receive 5-FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days and Mitomycin: 10 mg/m2, day 1 and 29 with IMRT radiation: 54 Gy in 30 fractions at 1.8 Gy per fraction.&#xD;
The 2-4th dosages of ADXS11-001 will not be until after completion of all chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of 10 days after completion of chemoradiation. The subsequent third and fourth treatment with of ADXS11 will be administered at 28 day intervals.&#xD;
Treatment: ADXS11-001 will be given at a dose of 1x109 cfu intravenously once every 28 days for 4 total doses. All 4 doses of ADXS11-001 will be 1x109 cfu.&#xD;
5FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days&#xD;
Mitomycin: 10 mg/m2, day 1 and 29 (day 29 can be + 7 days)&#xD;
IMRT: 54 Gy in 30 fractions at 1.8 Gy per fraction.</description>
          </group>
        </group_list>
        <measure>
          <title>To Evaluate Progression-free and Overall Survival for Patients With Anal Cancer Treated With ADXS11-001, Mitomycin, 5-FU and IMRT.</title>
          <description>Patients terminating study treatment early prior to disease recurrence will be followed every 6 months for year 1 then annually for a total of 5 years. The follow-up portion will commence once patient comes off study or post the 2-6 week post the 4th treatment time point/visit.&#xD;
Assessments were tumor evaluation via sigmoidoscopy, proctoscopy, colonoscopy or anoscope and also chest/abdomen/pelvic imaging.</description>
          <population>As one patient expired prior to 6 month assessment, the total n used was 9 to assess PFS</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <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="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>SAEs and AEs are captured from the time of consent until 30 days post the last treatment. SAEs occurring post 30 days are required to be reported if they are potentially related.</time_frame>
      <desc>Please note that all SAEs and AEs that occurred and were reported are noted in this database, but that does not mean that the SAEs or AEs reported here in the results table are related to the study drug ADXS11-001 or the combination. In short, these are SAEs or AEs that occurred, but the reporting of them here, does not equate to a relationship to study treatment.&#xD;
The SAEs include multiple events but this represents the actual SAE as reported by the site and as reported to NIH OBA and the FDA.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment</title>
          <description>The first dose will be given 10-14 days prior to the initiation of chemoradiation.&#xD;
Patient will then receive 5-FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days and Mitomycin: 10 mg/m2, day 1 and 29 with IMRT radiation: 54 Gy in 30 fractions at 1.8 Gy per fraction.&#xD;
The 2-4th dosages of ADXS11-001 will not be until after completion of all chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of 10 days after completion of chemoradiation. The subsequent third and fourth treatment with of ADXS11 will be administered at 28 day intervals.&#xD;
Treatment: ADXS11-001 will be given at a dose of 1x109 cfu intravenously once every 28 days for 4 total doses. All 4 doses of ADXS11-001 will be 1x109 cfu.&#xD;
5FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days&#xD;
Mitomycin: 10 mg/m2, day 1 and 29 (day 29 can be + 7 days)&#xD;
IMRT: 54 Gy in 30 fractions at 1.8 Gy per fraction.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</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="10" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>fever (1), hypotension(2)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>fever (1), hypotension(2) Hypokalemia (3)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>weakness (3), decreased appetite (2), GI bleed(3). Anemia(3)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea (3), dehydration (3), anal mucositis (3), enterocolitis (2)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea(3),dehydration(3),anal mucositis(3),</sub_title>
                <description>enterocolitis(2),colitis(2),perianal pain(3), diarrhea(2),weakness(2),Anemia(2)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Expired unknown reason (5)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>seizure (3), catastrophic pulmonary or cardiac event or massive CVA (5)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>PLT(4), diarrhea (2), ANC (3), fever (1)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhea (3), dehydration(3), wt loss (2), back pain (2), fatigue (2),</sub_title>
                <description>hypokalemia (3), HGB(3), PLT (2), Glucose (1), Hyponatremia (1), albumin(1), hypocalcemia (1), WBC (2), Lymph (4)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhea (2), wt loss (2) , back pain (1), fatigue (2),</sub_title>
                <description>HGB(2), PLT (3), Glucose-hyperglycemia (1), , albumin(2), hypocalcemia (2), WBC (2), Lymph (2), fever (2)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>fever (1) headache (1)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fever(1*)febrile neutropenia(3*)ANC(3*)WBC (4*), PLT (4*)</sub_title>
                <description>Anemia (3*)cellulitis (2*)acute kidney injury(2*)creatinine(2*)mucositis(1*)Lymph(4*)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>ANC (4*)WBC(4*)PLT(3*)Anemia (3*)cellulitis (2*),mucositis (1*)Lymph (4*),</sub_title>
                <description>thromboembolic event(2*),left lower leg edema(1*)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>chest pain (1*), shortness of breath (3*), lightheadedness (1*)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rectal bleeding (3*), Anemia (2*) , ANC(3*) , PLT(4*) , Fever (1*)</sub_title>
                <description>Dermatitis radiation (3*) , pain rectal (2*)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rectal bleeding (3*)Anemia (3*)ANC(4*)PLT(4*)Fever (1*)</sub_title>
                <description>Dermatitis radiation (3*)pain rectal (2*)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</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="8" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>allergies</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>ALT</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>anal mucositis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>ANC</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>anorexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>APTT</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>AST</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>chills/rigors</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>confusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>creatinine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>depression</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Frequent stools (non-diarrhea)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>fecal incontinence</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dyspnea/SOB</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>edema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>erythoderma/erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>dry skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>ejaculatory dysfunction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>fever</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>flu-like symptoms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>GI bleed/bloody diarrhea/rectal bleed</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>H/A</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hematuria</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperpigmentation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoalbumin</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hypohydrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>HypoK</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>HypoMG</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>INR</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lightheadedness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>lymphocyte decrease</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>migraine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>mucositis/mouth sores</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>myalgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>pain-abdomen</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>pain/back and neck</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>pain secondary to abcess/infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>pain-epigastric</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>pain-general</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>pain-joints</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>pain-leg</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>rectal pain/perianal pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>paresthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>PLT</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Radiation Dermatitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>skin ulceration/Groin sore</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>infection (cellulitis/small intestine, abscess, UTI, vaginal)</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>social circumstances</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>sore throat</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>tooth infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>urinary frequency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>urinary pain/dysuria</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>urinary retention</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>vomitng</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>WBC</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>wt loss</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </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>Howard Safran, MD</name_or_title>
      <organization>Brown University Oncology Research Group (BrUOG)</organization>
      <phone>4018633000</phone>
      <email>kayla_rosati@brown.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/NCT01671488
org study id: BrUOG 276
nct id: NCT01671488
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The main purpose of this study is to study the safety and effectiveness of ADXS11-001 when
      combined with standard chemotherapy and radiation treatment for anal cancer. ADXS11-001 is an
      investigational agent that is not approved by the FDA to treat anal cancer or any other
      cancer.
Novel treatments are needed in anal cancer. An important percentage of patients with locally
      advanced anal cancer will have persistent loco-regional disease or develop systemic
      metastases. Virtually all cases of anal cancer are related to infection by HPV. Anal cancer
      cells infected with HPV have the tumor associated antigen HPV E7. ADXS11-001 causes antigen
      presenting cells to be stimulated to facilitate immune cells to attack cancer cells
      expressing HPV E7. ADXS11-001, at the phase II dose of 1x109 CFU, has been shown to be safe
      in patients with advanced cervical cancer which also is caused by HPV infection. Anti-tumor
      activity and safety have been demonstrated in cervical cancer to single agent ADXS11-001 and
      the combination of ADXS11-001 and cisplatin chemotherapy. Data presented at ASCO 2012
      ADXS11-001 is currently being evaluated in women in the United States with cervical
      intraepithelial neoplasia. Radiation may augment the activity of ADXS11-001 increasing the
      exposure of tumor related antigens thereby increasing the chance for loco-regional disease
      eradication and preventing systemic recurrence. Therefore, ADXS11-001 may increase complete
      response, prevent recurrence disease and increase disease-free and overall survival in anal
      cancer. This protocol will develop sufficient preliminary safety and efficacy data to
      facilitate the investigation of ADXS11-001 in anal cancer within "NRG", the newly formed
      cooperative group based on the merger of the RTOG, NSABP and GOG.

      As described above, Phase I studies and preliminary data from phase II studies have
      demonstrated that ADXS11-001, 1x109 CFU, can be safely administered as a single agent and in
      combination with chemotherapy. For example in over 200 patients treated at the dose of
      1x109CFU there have been no cases of severe listeria bacteremia or grade 3 cardiopulmonary
      toxicity. However, since ADXS11-001 has not previously been administered with radiation, the
      primary objective of this study will be to establish the safety of the addition of ADXS11-001
      to chemoradiation for anal cancer. The following schedules will be assessed.

      • Treatment Schedule: The first dose will be given 10-14 days prior to the initiation of
      chemoradiation. The 2nd-4th dosages of ADXS11-001will not be until after completion of all
      chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of
      10 days after completion of chemoradiation, ANC > 1,000 cells/mm3, serum creatinine < 1.5
      mg/dl and all toxicities from chemoradiation have resolved to grade 2 or less. The subsequent
      third and fourth treatment with of ADXS11 will be administered at 28 day intervals. This will
      provide the needed safety data to evaluate Treatment Schedule #2.

      Standard treatment with mitomycin, 5-FU and radiation for anal cancer has substantial
      toxicity. In RTOG 9811, 74% of patients had grade 3/4 nonhematologic toxicity and 61% of
      patients had grade 3 or grade 4 hematologic toxicity from this regimen. Therefore, the
      toxicities of standard chemoradiation with mitomycin, 5-FU and radiation are well above the
      conventionally accepted parameters in a phase I study even prior to adding ADXS11-001.
      However, it is critical that the addition of ADXS-11-001 does not compromise the delivery of
      potentially curative standard chemoradiation for anal cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To Evaluate the Safety of the Addition of ADXS11-001 to Standard Chemoradiation for Patients With Anal Cancer.
time frame: Baseline, then prior to each ADXS11-001 and weekly during radiation. Assessments 1-2 weeks post radiation then 2-6 weeks post vaccine and off study and 30 days post treatment.
description: Evaluate maximal toxicities via CTCAE version 4.0 All adverse events, serious and non-serious, were captured from date of ICF through 4 weeks post treatment completion- regardless of causality.
measure: To Evaluate the 6-month Clinical Complete Response Rate for Patients With Anal Cancer Treated With ADXS11-001 Mitomycin, 5-FU and IMRT.
time frame: Tumor evaluation 6 months after coming off study
description: Patients to undergo tumor evaluation assessment (via sigmoidoscopy, proctoscopy, colonoscopy or anoscope) 6 months post the start of chemotherapy/radiation.
measure: To Evaluate Progression-free and Overall Survival for Patients With Anal Cancer Treated With ADXS11-001, Mitomycin, 5-FU and IMRT.
time frame: Follow up and survival status at 6 months and 1 year post coming off study and annually until patient has been off for 5 years
description: Patients terminating study treatment early prior to disease recurrence will be followed every 6 months for year 1 then annually for a total of 5 years. The follow-up portion will commence once patient comes off study or post the 2-6 week post the 4th treatment time point/visit.
Assessments were tumor evaluation via sigmoidoscopy, proctoscopy, colonoscopy or anoscope and also chest/abdomen/pelvic imaging.
arm group label: Treatment
arm group type: Experimental
description: The first dose will be given 10-14 days prior to the initiation of chemoradiation.
Patient will then receive 5-FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days and Mitomycin: 10 mg/m2, day 1 and 29 with IMRT radiation: 54 Gy in 30 fractions at 1.8 Gy per fraction.
The 2-4th dosages of ADXS11-001 will not be until after completion of all chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of 10 days after completion of chemoradiation. The subsequent third and fourth treatment with of ADXS11 will be administered at 28 day intervals.
intervention type: Biological
intervention name: Treatment
description: ADXS11-001 will be given at a dose of 1x109 cfu intravenously once every 28 days for 4 total doses. All 4 doses of ADXS11-001 will be 1x109 cfu.
arm group label: Treatment
other name: ADXS11-001
intervention type: Drug
intervention name: 5FU
description: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days
arm group label: Treatment
intervention type: Drug
intervention name: Mitomycin
description: 10 mg/m2, day 1 and 29 (day 29 can be + 7 days)
arm group label: Treatment
intervention type: Radiation
intervention name: IMRT
description: 54 Gy in 30 fractions at 1.8 Gy per fraction.
arm group label: Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Howard Safran, MD
role: Principal Investigator
affiliation: Brown University
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brown University
investigator full name: howard safran
investigator title: Principal Investigator
mesh term: Anus Neoplasms
mesh term: Mitomycins
mesh term: Mitomycin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 