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/NCT06008275</url>
    </required_header>
    <id_info>
      <org_study_id>NerRux</org_study_id>
      <nct_id>NCT06008275</nct_id>
    </id_info>
    <brief_title>Neratinib in Combination With Ruxolitinib in Patients With mTNBC</brief_title>
    <official_title>Pilot Clinical Trial Examining the Safety and Efficacy of Neratinib in Combination With Ruxolitinib in Patients With Chemotherapy-pretreated Metastatic Triple Negative Breast Cancer With Chest Wall Recurrence</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Baylor Research Institute</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Baylor Research Institute</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this clinical trial is to assess the safety and efficacy of combined ruxolitinib&#xD;
        and neratinib in patients with chemotherapy-pretreated metastatic triple negative breast&#xD;
        cancer. This trial will evaluate one dosing schedule of neratinib in ruxolitinib in patients&#xD;
        with metTNBC with locoregional recurrence.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Metastatic triple negative breast cancer (metTNBC) lacks expression of estrogen receptor&#xD;
        (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), making&#xD;
        it unresponsive to both endocrine and HER2-targeted therapies. Chest wall recurrence is&#xD;
        common in patients with treatment resistant metTNBC and leads to substantial morbidity as no&#xD;
        successful therapeutic options exist. Patients suffer with escalated progression of disease&#xD;
        across the entire chest wall with substantial wound control issues. Chest wall recurrence&#xD;
        generally occurs within one year following chemotherapy or immunotherapy given with curative&#xD;
        intent, and in general signifies metTNBC that is primary resistant to standard therapy.&#xD;
  &#xD;
        There is long standing evidence that EGFR is an important signaling pathway in metTNBC as&#xD;
        this cancer overexpresses EGFR compared to other breast cancer subtypes. This exposes a&#xD;
        pathway that is targetable for treatment, making EGFR a compelling molecular therapeutic&#xD;
        target in metTNBC. Another key contributor to progression of TNBC is the JAK/STAT3 signaling&#xD;
        pathway and assessments of EGFR have shown that it is a positive regulator of STAT3 that&#xD;
        drives proliferation and survival of metTNBC.&#xD;
  &#xD;
        The investigators hypothesize that combined inhibition of EGFR and JAK/STAT3 using neratinib&#xD;
        and ruxolitinib will lead to greater inhibition of the critically important EGFR pathway in&#xD;
        TNBC with greater efficacy than targeting EGFR or JAK/STAT3 alone.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 2023</start_date>
    <completion_date type="Anticipated">December 2025</completion_date>
    <primary_completion_date type="Anticipated">June 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>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Health Services Research</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Objective Response Rate</measure>
      <time_frame>18 months</time_frame>
      <description>Calculate objective response rate (CR+PR) associated with neratinib in combination ruxolitinib. Objective response rate will be calculated by defining the proportion of patients who have a complete or partial response to the study therapy, as determined by the treating physician.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Duration of Response</measure>
      <time_frame>18 months</time_frame>
      <description>Calculate duration of response associated with neratinib in combination with ruxolitinib. Duration of response will be calculated from the time of tumor response to disease progression in patients responding to study therapy</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Genetic Evaluation</measure>
      <time_frame>18 months</time_frame>
      <description>Signaling signatures of research biopsies will be analyzed via Next Generation Sequencing and Reverse Phase Protein Array</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Metastatic Triple-Negative Breast Carcinoma</condition>
    <condition>Breast Cancer</condition>
    <arm_group>
      <arm_group_label>neratinib + ruxolitinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>There is only one arm</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Neratinib Oral Tablet</intervention_name>
      <description>240mg oral daily. Dosing will follow standard dose escalation procedures</description>
      <arm_group_label>neratinib + ruxolitinib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ruxolitinib Oral Tablet</intervention_name>
      <description>20mg oral twice daily. Dosing will follow standard initial dose recommendation procedure</description>
      <arm_group_label>neratinib + ruxolitinib</arm_group_label>
      <other_name>Jakafi</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  A patient will be considered for enrollment in this study if all the following&#xD;
               criteria are met:&#xD;
  &#xD;
                 1. Female patients ≥18 years of age&#xD;
  &#xD;
                 2. Have a diagnosis of metastatic TNBC previously treated with standard&#xD;
                    anthracycline, cyclophosphamide, and taxane chemotherapy, unless there was a&#xD;
                    contraindication to doxorubicin, in which case prior treatment with this agent is&#xD;
                    not required.&#xD;
  &#xD;
                    Note. TNBC defined as ER-negative tumors with ≤10% tumor nuclei immunoreactivity,&#xD;
                    or &quot;ER Low Positive&quot; as defined by the updated ASCO/CAP guidelines 2020.&#xD;
  &#xD;
                 3. Have not received more than 4 prior chemotherapy regimens for metastatic disease.&#xD;
                    Prior platinum and/or taxane therapy in the adjuvant or metastatic setting is&#xD;
                    permitted. Patients with more than 4 prior regimens may be allowed on study per&#xD;
                    physician discretion, if ECOG PS is 0-1.&#xD;
  &#xD;
                 4. Have locoregional (e.g., breast, chest wall, regional lymphatic) or pulmonary or&#xD;
                    hepatic metastatic disease that is amenable to core needle biopsy. If a research&#xD;
                    biopsy from a patient's metastatic disease cannot be safely obtained, a skin&#xD;
                    biopsy is permitted. If a skin biopsy cannot be safely obtained, patients may&#xD;
                    still be eligible, per physician discretion.&#xD;
  &#xD;
                 5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1&#xD;
  &#xD;
                 6. Have adequate hematologic function, defined by:&#xD;
  &#xD;
                      1. Absolute neutrophil count (ANC) &gt;1500/µL&#xD;
  &#xD;
                      2. Platelet count ≥100,000/ µL&#xD;
  &#xD;
                      3. Hemoglobin ≥9 g/dL or ≥5.6 mmol/L&#xD;
  &#xD;
                 7. Have adequate liver function, defined by:&#xD;
  &#xD;
                      1. AST and ALT ≤2.5 x the upper limit of normal (ULN) or ≤5 x ULN in presence&#xD;
                         of liver metastases&#xD;
  &#xD;
                      2. Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for patients with total&#xD;
                         bilirubin levels &gt;1.5 × ULN&#xD;
  &#xD;
                 8. Have adequate renal function, defined by:&#xD;
  &#xD;
                    a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥30 mL/min&#xD;
  &#xD;
                 9. Patients who have a history of brain metastasis are eligible for the study&#xD;
                    provided that all the following criteria are met:&#xD;
  &#xD;
                10. Brain metastases which have been treated&#xD;
  &#xD;
                11. Off-treatment with steroids before administration of the first dose of treatment&#xD;
  &#xD;
                12. No ongoing requirement for dexamethasone or anti-epileptic drugs&#xD;
  &#xD;
                13. No clinical or radiological evidence of progression of brain metastases&#xD;
  &#xD;
                14. Patients must be accessible for treatment and follow-up.&#xD;
  &#xD;
                15. All patients must be able to understand the investigational nature of the study&#xD;
                    and give written informed consent prior to study entry.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  A patient will be ineligible for inclusion in this study any of the following criteria&#xD;
               are met:&#xD;
  &#xD;
                 1. Has received a live vaccine or live-attenuated vaccine within 30 days of the&#xD;
                    first dose of study treatment. Administration of killed vaccines is allowed.&#xD;
  &#xD;
                 2. Has peripheral neuropathy ≥grade 2&#xD;
  &#xD;
                 3. Has completed previous radiotherapy for metastatic disease &lt;2 weeks prior to&#xD;
                    study treatment initiation&#xD;
  &#xD;
                 4. Has an active infection requiring systemic therapy&#xD;
  &#xD;
                 5. Has significant cardiovascular disease, such as:&#xD;
  &#xD;
                      1. History of myocardial infarction, acute coronary syndrome, or coronary&#xD;
                         angioplasty/stenting/bypass grafting within the last 6 months&#xD;
  &#xD;
                      2. Congestive heart failure (CHF) New York Heart Association (NYHA) Class&#xD;
                         II-IV, or history of CHF NYHA class III or IV.&#xD;
  &#xD;
                 6. Has a known history of active tuberculosis&#xD;
  &#xD;
                 7. Women who are pregnant or lactating. All patients with reproductive potential&#xD;
                    must agree to use effective contraception from time of study entry until at least&#xD;
                    3 months after the last administration of study drug.&#xD;
  &#xD;
                 8. Patients who have any severe and/or uncontrolled medical conditions or other&#xD;
                    conditions that could affect their participation such as:&#xD;
  &#xD;
                      1. severe impaired lung functions as defined as spirometry and DLCO that is 50%&#xD;
                         of the normal predicted value and/or O2 saturation that is 88% or less at&#xD;
                         rest on room air&#xD;
  &#xD;
                      2. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh&#xD;
                         class C).&#xD;
  &#xD;
                 9. Has a history or current evidence of any condition, therapy, or laboratory&#xD;
                    abnormality that might confound the results of the study, interfere with the&#xD;
                    patient's full participation for the full duration of the study, or is not in the&#xD;
                    best interest of the patient to participate, in the opinion of the Treating&#xD;
                    Physician.&#xD;
  &#xD;
                10. Has received prior systemic anti-cancer therapy within 2 weeks prior to study&#xD;
                    treatment.&#xD;
  &#xD;
                11. Has received investigational agents within 4 weeks prior to study treatment.&#xD;
                    Monoclonal antibody agents should have a 4-week (28 day) washout period.&#xD;
  &#xD;
                12. Any other investigational or anti-cancer treatments while participating in this&#xD;
                    study&#xD;
  &#xD;
                13. Any other active malignancy&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Joyce A O'Shaughnessy, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Baylor Scott and White Research Institute</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Page E Blas, MA</last_name>
      <phone>214-820-5424</phone>
      <email>page.blas@bswhealth.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>Baylor University Medical Center, Baylor Charles A Sammons Cancer Center</name>
        <address>
          <city>Dallas</city>
          <state>Texas</state>
          <zip>75246</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Page E Blas, MA</last_name>
        <phone>214-820-5424</phone>
        <email>page.blas@bswhealth.org</email>
      </contact>
      <investigator>
        <last_name>Joyce A O'Shaughnessy, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 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>Breast Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</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/NCT06008275
  org study id: NerRux
  nct id: NCT06008275
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  The goal of this clinical trial is to assess the safety and efficacy of combined ruxolitinib
        and neratinib in patients with chemotherapy-pretreated metastatic triple negative breast
        cancer. This trial will evaluate one dosing schedule of neratinib in ruxolitinib in patients
        with metTNBC with locoregional recurrence.
  Metastatic triple negative breast cancer (metTNBC) lacks expression of estrogen receptor
        (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), making
        it unresponsive to both endocrine and HER2-targeted therapies. Chest wall recurrence is
        common in patients with treatment resistant metTNBC and leads to substantial morbidity as no
        successful therapeutic options exist. Patients suffer with escalated progression of disease
        across the entire chest wall with substantial wound control issues. Chest wall recurrence
        generally occurs within one year following chemotherapy or immunotherapy given with curative
        intent, and in general signifies metTNBC that is primary resistant to standard therapy.
  
        There is long standing evidence that EGFR is an important signaling pathway in metTNBC as
        this cancer overexpresses EGFR compared to other breast cancer subtypes. This exposes a
        pathway that is targetable for treatment, making EGFR a compelling molecular therapeutic
        target in metTNBC. Another key contributor to progression of TNBC is the JAK/STAT3 signaling
        pathway and assessments of EGFR have shown that it is a positive regulator of STAT3 that
        drives proliferation and survival of metTNBC.
  
        The investigators hypothesize that combined inhibition of EGFR and JAK/STAT3 using neratinib
        and ruxolitinib will lead to greater inhibition of the critically important EGFR pathway in
        TNBC with greater efficacy than targeting EGFR or JAK/STAT3 alone.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Health Services Research
  masking: None (Open Label)
  measure: Objective Response Rate
  time frame: 18 months
  description: Calculate objective response rate (CR+PR) associated with neratinib in combination ruxolitinib. Objective response rate will be calculated by defining the proportion of patients who have a complete or partial response to the study therapy, as determined by the treating physician.
  measure: Duration of Response
  time frame: 18 months
  description: Calculate duration of response associated with neratinib in combination with ruxolitinib. Duration of response will be calculated from the time of tumor response to disease progression in patients responding to study therapy
  measure: Genetic Evaluation
  time frame: 18 months
  description: Signaling signatures of research biopsies will be analyzed via Next Generation Sequencing and Reverse Phase Protein Array
  arm group label: neratinib + ruxolitinib
  arm group type: Experimental
  description: There is only one arm
  intervention type: Drug
  intervention name: Neratinib Oral Tablet
  description: 240mg oral daily. Dosing will follow standard dose escalation procedures
  arm group label: neratinib + ruxolitinib
  intervention type: Drug
  intervention name: Ruxolitinib Oral Tablet
  description: 20mg oral twice daily. Dosing will follow standard initial dose recommendation procedure
  arm group label: neratinib + ruxolitinib
  other name: Jakafi
  criteria: 
  gender: Female
  gender based: Yes
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Joyce A O'Shaughnessy, MD
  role: Principal Investigator
  affiliation: Baylor Scott and White Research Institute
  last name: Page E Blas, MA
  phone: 214-820-5424
  email: page.blas@bswhealth.org
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Breast Neoplasms
  sharing ipd: Undecided