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/NCT05969496</url>
    </required_header>
    <id_info>
      <org_study_id>22-1669.cc</org_study_id>
      <nct_id>NCT05969496</nct_id>
    </id_info>
    <brief_title>Neoadjuvant Pembrolizumab and Axitinib in Renal Cell Carcinoma With Associated Inferior Vena Cava Tumor Thrombus (NEOPAX)</brief_title>
    <acronym>NEOPAX</acronym>
    <official_title>Neoadjuvant Pembrolizumab and Axitinib in Renal Cell Carcinoma With Associated Inferior Vena Cava Tumor Thrombus (NEOPAX)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Colorado, Denver</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Cancer League of Colorado</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Colorado, Denver</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        The primary objective of this study is to evaluate whether the combination of Pembrolizumab&#xD;
        and Axitinib given in the neoadjuvant setting can decrease the Inferior Vena Cava Tumor&#xD;
        Thrombus burden. A decrease in the size of the tumor thrombus can potentially lead to&#xD;
        decrease in surgical complications, improve patient related health outcomes, and improve long&#xD;
        term outcomes such as progression free survival and overall survival.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Patients will receive the combination of Axitinib 5 mg orally twice daily (can be increased&#xD;
        to 7 mg twice daily after 2 weeks, and further to 10 mg twice daily as tolerated) and&#xD;
        Pembrolizumab 200 mg IV every 21 days. This combination will be given for a total of 12 weeks&#xD;
        (4 cycles). A radiographic assessment will be done up to 12 weeks (4 cycles of therapy) to&#xD;
        evaluate the primary endpoint of IVC TT response. Patients will undergo a definitive surgery&#xD;
        per treating urologist within 2 weeks (+/- 7 days) after the end of treatment scan.&#xD;
  &#xD;
        During the course of the trial, patient-related health outcomes using Kidney Cancer validated&#xD;
        questionnaires with FKSI-DRS and FKSI-19 will also be obtained. These are validated paper&#xD;
        questionnaires that will be given to each patient on study visits while receiving neoadjuvant&#xD;
        therapy.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 2023</start_date>
    <completion_date type="Anticipated">March 2029</completion_date>
    <primary_completion_date type="Anticipated">March 2027</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Evaluate IVC Tumor Thrombus Decrease Based on the Mayo Classification</measure>
      <time_frame>2 years</time_frame>
      <description>The combination therapy with Pembrolizumab and Axitinib is known to be active for advanced RCC. The Mayo classification is an established way of classifying the extent of the IVC TT which could be used as a parameter to evaluate response to therapy. The Mayo classification only quantifies the height of the TT which underestimates the response to therapy. Measuring the change in maximal anteroposterior and transverse diameter optimizes measurement of treatment response.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Evaluate a Decrease in IVC TT Size from Baseline</measure>
      <time_frame>2 years</time_frame>
      <description>The combination therapy with Pembrolizumab and Axitinib is known to be active for advanced RCC. The Mayo classification is an established way of classifying the extent of the IVC TT which could be used as a parameter to evaluate response to therapy. The Mayo classification only quantifies the height of the TT which underestimates the response to therapy. Measuring the change in maximal anteroposterior and transverse diameter optimizes measurement of treatment response.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Evaluate Surgical Complications after the Neoadjuvant Combination of Pembrolizumab and Axitinib Among Patients with RCC with IVC TT</measure>
      <time_frame>3 years</time_frame>
      <description>Surgical complication as defined by the Clavien-Dindo classification. The Clavien-Dindo classification is established and validated to describe surgical complications. This trial aims to evaluate improvement in surgical outcomes with neoadjuvant therapy making this method of describing at classifying perioperative morbidity.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety of the neoadjuvant therapy with the combination of Pembrolizumab and Axitinib among patients with RCCs with IVC TT by Adverse Events</measure>
      <time_frame>3 years</time_frame>
      <description>Evaluate the safety of the neoadjuvant therapy with the combination of Pembrolizumab and Axitinib among patients with RCCs with IVC TT by Adverse Events.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determine PFS</measure>
      <time_frame>1 year</time_frame>
      <description>Progression-free survival is defined as any clinical or radiographic progression or death from any cause one year after enrollment in the study</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival</measure>
      <time_frame>1 year</time_frame>
      <description>One year- Overall survival. Overall survival is defined as death from any cause one year after enrollment in the study</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Renal Cancer</condition>
    <condition>Kidney Cancer</condition>
    <condition>Renal Cell Carcinoma</condition>
    <condition>Inferior Vena Cava Thrombosis</condition>
    <arm_group>
      <arm_group_label>Combination Pembrolizumab and Axitinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Neoadjuvant therapy with the combination of Pembrolizumab and Axitinib will be given for eligible RCC patients with an IVC TT for a total of 12 weeks. Patients will then undergo imaging with a contrast enhanced, diffusion weighted imaging MRI of the abdomen to evaluate the IVC TT response. A CT chest will also be done to ensure there is no progression of disease. Patients can undergo definitive surgery per treating Urologist within 2 weeks (+/- 7 days) after end of treatment scan.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Axitinib</intervention_name>
      <description>Axitinib is a potent oral, vascular endothelial growth factor, c-kit and platelet derived growth factor inhibitor.</description>
      <arm_group_label>Combination Pembrolizumab and Axitinib</arm_group_label>
      <other_name>Inlyta</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pembrolizumab</intervention_name>
      <description>Pembrolizumab is a type of immunotherapy. It stimulates the body's immune system to fight cancer cells. Pembrolizumab targets and blocks a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells.</description>
      <arm_group_label>Combination Pembrolizumab and Axitinib</arm_group_label>
      <other_name>Keytruda</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Provision to sign and date the consent form.&#xD;
  &#xD;
            -  Stated willingness to comply with all study procedures and be available for the&#xD;
               duration of the study.&#xD;
  &#xD;
            -  Participant self-identified gender ages &gt;/= 18 years old is acceptable and appropriate&#xD;
               if they meet other inclusion criteria.&#xD;
  &#xD;
            -  Histologically proven clear cell component RCC.&#xD;
  &#xD;
            -  An upfront candidate for definitive surgery per treating Urologist.&#xD;
  &#xD;
            -  Suitable for and willing to undergo nephrectomy (either cytoreductive or with curative&#xD;
               intent) per treating urologist.&#xD;
  &#xD;
            -  T Stage of any of the following: cT3b, cT3c, cT4&#xD;
  &#xD;
            -  N stage of any of the following: cN0 or cN1&#xD;
  &#xD;
            -  M stage of any of the following: cM0 or cM1&#xD;
  &#xD;
            -  ECOG performance status 0 - 2.&#xD;
  &#xD;
            -  Urinalysis &lt;2+ protein. If dipstick is ≥2+ then a 24-hour urine collection should be&#xD;
               performed, and the patient may enter the trial if urinary protein is &lt;2g per 24 hours.&#xD;
  &#xD;
            -  All participants who have reproductive potential must have a negative serum or urine&#xD;
               pregnancy test within a maximum of 14 days prior to starting trial treatment.&#xD;
  &#xD;
          Reproductive potential is defined as the following:&#xD;
  &#xD;
            -  Women will be considered post-menopausal if they have been amenorrheic for 12 months&#xD;
               without an alternative medical cause. The following age-specific requirements apply:&#xD;
  &#xD;
                 -  Women &lt;50 years of age would be considered post-menopausal if they have been&#xD;
                    amenorrheic for 12 months or more following cessation of exogenous hormonal&#xD;
                    treatments and if they have luteinizing hormone and follicle-stimulating hormone&#xD;
                    levels in the post-menopausal range for the institution or underwent surgical&#xD;
                    sterilization (bilateral oophorectomy or hysterectomy)&#xD;
  &#xD;
                 -  Women ≥50 years of age would be considered post-menopausal if they have been&#xD;
                    amenorrheic for 12 months or more following cessation of all exogenous hormonal&#xD;
                    treatments, had radiation-induced menopause with last menses &gt;1 year ago, had&#xD;
                    chemotherapy-induced menopause with last menses &gt;1 year ago, or underwent&#xD;
                    surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or&#xD;
                    hysterectomy&#xD;
  &#xD;
                 -  For males with reproductive potential, use effective birth control during&#xD;
                    treatment with Axitinib and Pembrolizumab is recommended.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Is currently participating in or has participated in a study of an investigational&#xD;
               agent or has used an investigational device within 4 weeks prior to enrollment.&#xD;
  &#xD;
            -  Has had major surgery within 4 weeks or received radiation therapy within 1 week prior&#xD;
               to enrollment to the study.&#xD;
  &#xD;
            -  Has had prior treatment with any anti-programmed cell death (anti-PD-1) or programmed&#xD;
               cell death ligand 1 (PD-L1), or an antibody targeting any other immune-regulatory&#xD;
               receptors or mechanisms.&#xD;
  &#xD;
            -  Has received prior systemic anti-cancer therapy for RCC with vascular endothelial&#xD;
               growth factor (VEGF)/VEGF receptors (VEGFR).&#xD;
  &#xD;
            -  Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema,&#xD;
               hypotension, bronchospasm, angioedema, or anaphylaxis) to Axitinib.&#xD;
  &#xD;
            -  Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy greater&#xD;
               than Prednisone 10 mg daily or a steroid equivalent, or any other form of&#xD;
               immunosuppressive therapy within 7 days prior to enrollment to the study except in the&#xD;
               case of central nervous system (CNS) metastases.&#xD;
  &#xD;
            -  Has an active autoimmune disease requiring systemic treatment within the past 2 years&#xD;
               OR a documented history of clinically severe autoimmune disease. Note: Participants&#xD;
               with vitiligo, Sjogren's syndrome, Type 1 diabetes, resolved childhood asthma/atopy,&#xD;
               hypothyroidism or adrenal or pituitary insufficiency who are stable on hormone&#xD;
               replacement are not excluded.&#xD;
  &#xD;
            -  Has a known additional malignancy that has progressed or has required active treatment&#xD;
               in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma&#xD;
               of the skin, superficial bladder cancer, or carcinoma in situ such as breast cancer in&#xD;
               situ, thyroid cancer (papillary, hurthle cell or follicular), or localized prostate&#xD;
               cancer are acceptable if they have undergone potentially curative therapy.&#xD;
  &#xD;
            -  Has known active CNS metastases and/or carcinomatous meningitis.&#xD;
  &#xD;
            -  Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
               pneumonitis.&#xD;
  &#xD;
            -  ALT or AST above 3 times the upper limit of normal&#xD;
  &#xD;
            -  Has received a live virus vaccine within 30 days of enrollment to the study.&#xD;
  &#xD;
            -  Active GI bleeding, as evidenced by hematemesis, hematochezia, or melena in the past 3&#xD;
               months without evidence of resolution documented by endoscopy or colonoscopy.&#xD;
  &#xD;
            -  Intraluminal metastatic lesion with suspected bleeding, inflammatory bowel disease,&#xD;
               ulcerative colitis or other GI condition associated with increased risk of&#xD;
               perforation.&#xD;
  &#xD;
            -  Has QT interval corrected for heart rate (QTc) ≥480 msec.&#xD;
  &#xD;
            -  Has a history of any of the following cardiovascular conditions within 12 months of&#xD;
               enrollment to the study:&#xD;
  &#xD;
                 -  Myocardial infarction&#xD;
  &#xD;
                 -  Unstable angina pectoris&#xD;
  &#xD;
                 -  Cardiac angioplasty or stenting&#xD;
  &#xD;
                 -  Coronary/peripheral artery bypass graft&#xD;
  &#xD;
                 -  Class III or IV congestive heart failure per New York Heart Association&#xD;
  &#xD;
                 -  Cerebrovascular accident or transient ischemic attack&#xD;
  &#xD;
            -  Has poorly controlled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg&#xD;
               and/or diastolic blood pressure (DBP) ≥90 mm Hg on 3 or more dose optimized anti-&#xD;
               hypertensive medication.&#xD;
  &#xD;
            -  Has evidence of inadequate wound healing per treating physician discretion.&#xD;
  &#xD;
            -  Has active bleeding disorder or other history of significant bleeding episodes within&#xD;
               30 days of enrollment to the study.&#xD;
  &#xD;
            -  Has current use (within 7 days of enrollment) or anticipated need for treatment with&#xD;
               drugs or foods that are known to be strong cytochrome P450 (CYP3A4/5) inhibitors.&#xD;
  &#xD;
            -  Has current use (within 7 days of enrollment) or anticipated need for treatment with&#xD;
               drugs that are known strong CYP3A4/5 inducers, including but not limited to&#xD;
               carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort; or&#xD;
               drugs that are known with proarrhythmic potential.&#xD;
  &#xD;
            -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
               cooperation with the requirements of the study by subject self-report.&#xD;
  &#xD;
            -  Has had a prior solid organ transplant.&#xD;
  &#xD;
            -  Is pregnant or breastfeeding or expecting to conceive or father children within the&#xD;
               projected duration of the study, starting with the screening visit through 120 days&#xD;
               after the last dose of study drug.&#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>Elizabeth E Kessler, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Colorado, Denver</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Matthew Lee</last_name>
      <phone>720-848-0630</phone>
      <email>matthew.lee@cuanscutz.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>University of Colorado Cancer Center</name>
        <address>
          <city>Aurora</city>
          <state>Colorado</state>
          <zip>80045</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>July 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 24, 2023</last_update_submitted>
    <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 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>Carcinoma</mesh_term>
      <mesh_term>Carcinoma, Renal Cell</mesh_term>
      <mesh_term>Kidney Neoplasms</mesh_term>
      <mesh_term>Thrombosis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pembrolizumab</mesh_term>
      <mesh_term>Axitinib</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/NCT05969496
  org study id: 22-1669.cc
  nct id: NCT05969496
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The primary objective of this study is to evaluate whether the combination of Pembrolizumab
        and Axitinib given in the neoadjuvant setting can decrease the Inferior Vena Cava Tumor
        Thrombus burden. A decrease in the size of the tumor thrombus can potentially lead to
        decrease in surgical complications, improve patient related health outcomes, and improve long
        term outcomes such as progression free survival and overall survival.
  Patients will receive the combination of Axitinib 5 mg orally twice daily (can be increased
        to 7 mg twice daily after 2 weeks, and further to 10 mg twice daily as tolerated) and
        Pembrolizumab 200 mg IV every 21 days. This combination will be given for a total of 12 weeks
        (4 cycles). A radiographic assessment will be done up to 12 weeks (4 cycles of therapy) to
        evaluate the primary endpoint of IVC TT response. Patients will undergo a definitive surgery
        per treating urologist within 2 weeks (+/- 7 days) after the end of treatment scan.
  
        During the course of the trial, patient-related health outcomes using Kidney Cancer validated
        questionnaires with FKSI-DRS and FKSI-19 will also be obtained. These are validated paper
        questionnaires that will be given to each patient on study visits while receiving neoadjuvant
        therapy.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Evaluate IVC Tumor Thrombus Decrease Based on the Mayo Classification
  time frame: 2 years
  description: The combination therapy with Pembrolizumab and Axitinib is known to be active for advanced RCC. The Mayo classification is an established way of classifying the extent of the IVC TT which could be used as a parameter to evaluate response to therapy. The Mayo classification only quantifies the height of the TT which underestimates the response to therapy. Measuring the change in maximal anteroposterior and transverse diameter optimizes measurement of treatment response.
  measure: Evaluate a Decrease in IVC TT Size from Baseline
  time frame: 2 years
  description: The combination therapy with Pembrolizumab and Axitinib is known to be active for advanced RCC. The Mayo classification is an established way of classifying the extent of the IVC TT which could be used as a parameter to evaluate response to therapy. The Mayo classification only quantifies the height of the TT which underestimates the response to therapy. Measuring the change in maximal anteroposterior and transverse diameter optimizes measurement of treatment response.
  measure: Evaluate Surgical Complications after the Neoadjuvant Combination of Pembrolizumab and Axitinib Among Patients with RCC with IVC TT
  time frame: 3 years
  description: Surgical complication as defined by the Clavien-Dindo classification. The Clavien-Dindo classification is established and validated to describe surgical complications. This trial aims to evaluate improvement in surgical outcomes with neoadjuvant therapy making this method of describing at classifying perioperative morbidity.
  measure: Safety of the neoadjuvant therapy with the combination of Pembrolizumab and Axitinib among patients with RCCs with IVC TT by Adverse Events
  time frame: 3 years
  description: Evaluate the safety of the neoadjuvant therapy with the combination of Pembrolizumab and Axitinib among patients with RCCs with IVC TT by Adverse Events.
  measure: Determine PFS
  time frame: 1 year
  description: Progression-free survival is defined as any clinical or radiographic progression or death from any cause one year after enrollment in the study
  measure: Overall Survival
  time frame: 1 year
  description: One year- Overall survival. Overall survival is defined as death from any cause one year after enrollment in the study
  arm group label: Combination Pembrolizumab and Axitinib
  arm group type: Experimental
  description: Neoadjuvant therapy with the combination of Pembrolizumab and Axitinib will be given for eligible RCC patients with an IVC TT for a total of 12 weeks. Patients will then undergo imaging with a contrast enhanced, diffusion weighted imaging MRI of the abdomen to evaluate the IVC TT response. A CT chest will also be done to ensure there is no progression of disease. Patients can undergo definitive surgery per treating Urologist within 2 weeks (+/- 7 days) after end of treatment scan.
  intervention type: Drug
  intervention name: Axitinib
  description: Axitinib is a potent oral, vascular endothelial growth factor, c-kit and platelet derived growth factor inhibitor.
  arm group label: Combination Pembrolizumab and Axitinib
  other name: Inlyta
  intervention type: Drug
  intervention name: Pembrolizumab
  description: Pembrolizumab is a type of immunotherapy. It stimulates the body's immune system to fight cancer cells. Pembrolizumab targets and blocks a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells.
  arm group label: Combination Pembrolizumab and Axitinib
  other name: Keytruda
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Elizabeth E Kessler, MD
  role: Principal Investigator
  affiliation: University of Colorado, Denver
  last name: Matthew Lee
  phone: 720-848-0630
  email: matthew.lee@cuanscutz.edu
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Carcinoma, Renal Cell
  mesh term: Kidney Neoplasms
  mesh term: Thrombosis
  mesh term: Pembrolizumab
  mesh term: Axitinib
  sharing ipd: No