xml: <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/NCT06011772</url>
    </required_header>
    <id_info>
      <org_study_id>I 1578122</org_study_id>
      <nct_id>NCT06011772</nct_id>
    </id_info>
    <brief_title>EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer</brief_title>
    <official_title>A Phase 0 Study of EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Roswell Park Cancer Institute</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Roswell Park Cancer Institute</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to determine the immunogenicity of the CIMAvaxEGF® vaccine (that&#xD;
        is, its effectiveness in inducing an anti-tumor immune response) in patients with metastatic&#xD;
        KRAS/NRAS/BRAF wild-type gene colorectal cancer, when given in combination with standard&#xD;
        therapies used in the treatment of advanced colorectal cancer.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2, 2023</start_date>
    <completion_date type="Anticipated">October 2, 2026</completion_date>
    <primary_completion_date type="Anticipated">October 2, 2025</primary_completion_date>
    <phase>Early Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Immunogencity of vaccine</measure>
      <time_frame>up to 60 days after last dose</time_frame>
      <description>Percentage of patients with antibody titers greater than or equal to 1:4000 using a 90% confidence interval obtained by Jeffery's prior method</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Progression free survival</measure>
      <time_frame>time from treatment until disease progression, death or last follow up assesed up to 2 years</time_frame>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">42</enrollment>
    <condition>Colo-rectal Cancer</condition>
    <arm_group>
      <arm_group_label>Cohort A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.&#xD;
  MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 chemotherapy consisting of leucovorin IV, oxaliplatin IV over 2 hours, and fluorouracil IV and bevacizumab IV over 10 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort B1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.&#xD;
  MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive FOLFIRI consisting of irinotecan IV, leucovorin IV over 90 minutes, and fluorouracil IV and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort B2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.&#xD;
  MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 chemotherapy and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort C</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Description LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.&#xD;
  MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 and cetuximab, FOLFOX6 and bevacizumab, or mFOLFOX6 per investigators preference. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo metastasectomy 4-8 weeks after first maintenance phase dose. Patients undergo collection of blood samples throughout the trial.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine</intervention_name>
      <description>Given IM</description>
      <arm_group_label>Cohort A</arm_group_label>
      <arm_group_label>Cohort B1</arm_group_label>
      <arm_group_label>Cohort B2</arm_group_label>
      <arm_group_label>Cohort C</arm_group_label>
      <other_name>Cimavax</other_name>
      <other_name>CIMAvax EGF</other_name>
      <other_name>Epidermal Growth Factor (EGF) Vaccine</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Leucovorin</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Cohort A</arm_group_label>
      <arm_group_label>Cohort B1</arm_group_label>
      <arm_group_label>Cohort C</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Oxaliplatin</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Cohort A</arm_group_label>
      <arm_group_label>Cohort B2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fluorouracil</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Cohort A</arm_group_label>
      <arm_group_label>Cohort B1</arm_group_label>
      <arm_group_label>Cohort B2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Bevacizumab</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Cohort A</arm_group_label>
      <arm_group_label>Cohort C</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Irinotecan</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Cohort B1</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Cetuximab</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Cohort B1</arm_group_label>
      <arm_group_label>Cohort B2</arm_group_label>
      <arm_group_label>Cohort C</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Metastasectomy</intervention_name>
      <description>Undergo metastasectomy</description>
      <arm_group_label>Cohort C</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen collection</intervention_name>
      <description>Undergo collection of blood samples</description>
      <arm_group_label>Cohort B1</arm_group_label>
      <arm_group_label>Cohort B2</arm_group_label>
      <arm_group_label>Cohort C</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Histologically or cytologically confirmed metastatic adenocarcinoma of colon or rectum&#xD;
               that cannot be removed by surgery without prior systemic therapy for advanced disease&#xD;
               (prior adjuvant chemotherapy completed &gt;12 months from diagnosis of metastatic or&#xD;
               advanced disease is allowed) for cohorts A and C and with one prior line of therapy&#xD;
               but no more than 2 prior lines of therapy for advanced disease (prior adjuvant&#xD;
               chemotherapy completed &lt;12 months from diagnosis of metastatic or advanced disease is&#xD;
               considered one line of therapy).&#xD;
  &#xD;
                 -  Cohort A: May have received 1 cycle of mFOLFOX6± Bevacizumab pending results of&#xD;
                    RAS and BRAF. If results determine patient is eligible, the patient will be&#xD;
                    enrolled and will received the addition of CIMAvax + Bevacizumab in their second&#xD;
                    cycle.&#xD;
  &#xD;
                 -  Cohort B: Patients with RAS- and BRAF wild-type metastatic CRC who have received&#xD;
                    at least one but no more than 2 prior therapies for advanced disease&#xD;
  &#xD;
                 -  Cohort C: Patients with RAS- and BRAF wild-type metastatic CRC who have not&#xD;
                    received prior therapy for advanced disease and are candidates for liver&#xD;
                    metastasectomy (one cycle of standard therapy with mFOLFOX6 with or without&#xD;
                    appropriate biologic agent is allowed)&#xD;
  &#xD;
            -  KRAS/NRAS/BRAF (V600) wild-type.&#xD;
  &#xD;
            -  Have an ECOG Performance Status of 0 1. Refer to Appendix A.&#xD;
  &#xD;
            -  Patients must have adequate organ and marrow function as defined below:&#xD;
  &#xD;
                 -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L&#xD;
  &#xD;
                 -  Platelets ≥ 100 x 109/L&#xD;
  &#xD;
                 -  Hemoglobin ≥ 8 g/dL&#xD;
  &#xD;
                 -  Creatinine clearance&gt; 60 mL/min (Cockcroft-Gault Equation)&#xD;
  &#xD;
                 -  ALT and AST ≤ 3 x ULN (ALT and AST ≤ 5 x ULN is acceptable if liver metastases&#xD;
                    are present&#xD;
  &#xD;
                 -  Total bilirubin ≤ 1.5x ULN. For patients with well documented Gilbert's syndrome,&#xD;
                    total bilirubin ≤ 3x ULN with direct bilirubin within normal range&#xD;
  &#xD;
            -  Have measurable disease per RECIST 1.1 criteria present.&#xD;
  &#xD;
            -  Participants of child-bearing potential must agree to use adequate contraceptive&#xD;
               methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study&#xD;
               entry. Should a woman become pregnant or suspect she is pregnant while she or her&#xD;
               partner is participating in this study, she should inform her treating physician&#xD;
               immediately.&#xD;
  &#xD;
            -  Participant must understand the investigational nature of this study and sign an&#xD;
               Independent Ethics Committee/Institutional Review Board approved written informed&#xD;
               consent form prior to receiving any study related procedure.&#xD;
  &#xD;
            -  Participant agrees to provide tumor biopsy tissue while on study (cohort A and B) or&#xD;
               allow tissue to be taken during surgery (cohort C)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Toxicity ≥Grade 2 from prior chemotherapy.&#xD;
  &#xD;
            -  Other cancer requiring active treatment.&#xD;
  &#xD;
            -  Prior exposure to anti-EGFR monoclonal antibody (i.e. cetuximab or panitumumab) for&#xD;
               colorectal cancer treatment.&#xD;
  &#xD;
            -  Had major surgery within 4 weeks prior to starting study drug or has not recovered&#xD;
               from major side effects (tumor biopsy is not considered major surgery) resulting from&#xD;
               a prior surgery.&#xD;
  &#xD;
            -  Has known immunosuppressive disease (e.g. HIV, AIDS or other immune depressing&#xD;
               disease). Testing is not mandatory.&#xD;
  &#xD;
            -  Participants with known brain metastases should be excluded from this clinical trial&#xD;
               because of their poor prognosis and because they often develop progressive neurologic&#xD;
               dysfunction that would confound the evaluation of neurologic and other adverse events.&#xD;
  &#xD;
            -  Active, clinically serious infections or other serious uncontrolled medical conditions&#xD;
               or psychiatric illness/social situations that would limit compliance with study&#xD;
               requirements.&#xD;
  &#xD;
            -  History or current evidence of any condition, therapy, or laboratory abnormality that&#xD;
               might confound the results of the study, interfere with the patient's participation&#xD;
               for the full duration of the study, or is not in the best interest of the patient to&#xD;
               participate, in the opinion of the treating Investigator, including, but not limited&#xD;
               to:&#xD;
  &#xD;
                 -  Myocardial infarction or arterial thromboembolic events within 6 months prior to&#xD;
                    baseline or severe or unstable angina, New York Heart Association (NYHA) Class&#xD;
                    III or IV disease&#xD;
  &#xD;
                 -  History of documented congestive heart failure (New York Heart Association&#xD;
                    functional classification III or IV) within 6 months prior to baseline&#xD;
  &#xD;
                 -  Uncontrolled hypertension (SBP&gt;160/DBP&gt;100 despite medical intervention).&#xD;
  &#xD;
                 -  History of myocarditis of any etiology&#xD;
  &#xD;
                 -  History of ventricular arrhythmias&#xD;
  &#xD;
            -  Active major or clinically significant bleeding based on the International Society on&#xD;
               Thrombosis and Hemostasis definition.&#xD;
  &#xD;
            -  Pregnant or nursing female participants.&#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>Deepak Vadehra</last_name>
      <role>Principal Investigator</role>
      <affiliation>Roswell Park Comprehensive Cancer Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Deepak Vadehra</last_name>
      <phone>716-845-2300</phone>
      <email>askroswell@roswellpark.org</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Colorectal Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leucovorin</mesh_term>
      <mesh_term>Bevacizumab</mesh_term>
      <mesh_term>Cetuximab</mesh_term>
      <mesh_term>Fluorouracil</mesh_term>
      <mesh_term>Oxaliplatin</mesh_term>
      <mesh_term>Irinotecan</mesh_term>
      <mesh_term>Vaccines</mesh_term>
      <mesh_term>Monatide (IMS 3015)</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06011772
  org study id: I 1578122
  nct id: NCT06011772
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The purpose of this study is to determine the immunogenicity of the CIMAvaxEGF® vaccine (that
        is, its effectiveness in inducing an anti-tumor immune response) in patients with metastatic
        KRAS/NRAS/BRAF wild-type gene colorectal cancer, when given in combination with standard
        therapies used in the treatment of advanced colorectal cancer.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Immunogencity of vaccine
  time frame: up to 60 days after last dose
  description: Percentage of patients with antibody titers greater than or equal to 1:4000 using a 90% confidence interval obtained by Jeffery's prior method
  measure: Progression free survival
  time frame: time from treatment until disease progression, death or last follow up assesed up to 2 years
  arm group label: Cohort A
  arm group type: Experimental
  description: LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.
  MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 chemotherapy consisting of leucovorin IV, oxaliplatin IV over 2 hours, and fluorouracil IV and bevacizumab IV over 10 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.
  arm group label: Cohort B1
  arm group type: Experimental
  description: LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.
  MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive FOLFIRI consisting of irinotecan IV, leucovorin IV over 90 minutes, and fluorouracil IV and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.
  arm group label: Cohort B2
  arm group type: Experimental
  description: LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.
  MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 chemotherapy and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial
  arm group label: Cohort C
  arm group type: Experimental
  description: Description LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity.
  MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 and cetuximab, FOLFOX6 and bevacizumab, or mFOLFOX6 per investigators preference. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo metastasectomy 4-8 weeks after first maintenance phase dose. Patients undergo collection of blood samples throughout the trial.
  intervention type: Biological
  intervention name: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
  description: Given IM
  arm group label: Cohort A
  arm group label: Cohort B1
  arm group label: Cohort B2
  arm group label: Cohort C
  other name: Cimavax
  other name: CIMAvax EGF
  other name: Epidermal Growth Factor (EGF) Vaccine
  intervention type: Drug
  intervention name: Leucovorin
  description: Given IV
  arm group label: Cohort A
  arm group label: Cohort B1
  arm group label: Cohort C
  intervention type: Drug
  intervention name: Oxaliplatin
  description: Given IV
  arm group label: Cohort A
  arm group label: Cohort B2
  intervention type: Drug
  intervention name: Fluorouracil
  description: Given IV
  arm group label: Cohort A
  arm group label: Cohort B1
  arm group label: Cohort B2
  intervention type: Biological
  intervention name: Bevacizumab
  description: Given IV
  arm group label: Cohort A
  arm group label: Cohort C
  intervention type: Drug
  intervention name: Irinotecan
  description: Given IV
  arm group label: Cohort B1
  intervention type: Biological
  intervention name: Cetuximab
  description: Given IV
  arm group label: Cohort B1
  arm group label: Cohort B2
  arm group label: Cohort C
  intervention type: Procedure
  intervention name: Metastasectomy
  description: Undergo metastasectomy
  arm group label: Cohort C
  intervention type: Procedure
  intervention name: Biospecimen collection
  description: Undergo collection of blood samples
  arm group label: Cohort B1
  arm group label: Cohort B2
  arm group label: Cohort C
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Deepak Vadehra
  role: Principal Investigator
  affiliation: Roswell Park Comprehensive Cancer Center
  last name: Deepak Vadehra
  phone: 716-845-2300
  email: askroswell@roswellpark.org
  responsible party type: Sponsor
  mesh term: Colorectal Neoplasms
  mesh term: Leucovorin
  mesh term: Bevacizumab
  mesh term: Cetuximab
  mesh term: Fluorouracil
  mesh term: Oxaliplatin
  mesh term: Irinotecan
  mesh term: Vaccines
  mesh term: Monatide (IMS 3015)
  sharing ipd: No