<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/NCT04504331</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-53650</org_study_id>
    <secondary_id>BRS0113</secondary_id>
    <secondary_id>K08CA252457</secondary_id>
    <secondary_id>NCI-2020-13784</secondary_id>
    <nct_id>NCT04504331</nct_id>
  </id_info>
  <brief_title>Study of Infigratinib in Combination With Tamoxifen in Hormone Receptor Positive, HER2 Negative, FGFR Altered Advanced Breast Cancer</brief_title>
  <official_title>A Phase 1B Study of Infigratinib in Combination With Tamoxifen in Hormone Receptor Positive, HER2 Negative, FGFR Altered Advanced Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jennifer Lee Caswell-Jin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>QED Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is identify the dose(s) of infigratinib to use in combination with&#xD;
      tamoxifen to treat patients with a particular type of advanced breast cancer (hormone&#xD;
      receptor-positive, HER2-negative, FGFR-altered breast cancer)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objective: Determine the maximum (no greater than 125 mg) dose of infigratinib used&#xD;
      in combination with the FDA-approved dose and schedule of tamoxifen (Cohort 1) in terms of&#xD;
      the number of dose-limiting toxicities observed in the first 2 cycles of therapy in subjects&#xD;
      with hormone receptor-positive, HER2-negative advanced breast cancer.&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
        -  Estimate the incidence of treatment-emergent adverse events (serious and non-serious).&#xD;
&#xD;
        -  Estimate the objective tumor response rate (ORR) in subjects with measurable disease.&#xD;
&#xD;
        -  Estimate the progression-free survival (PFS).&#xD;
&#xD;
        -  Estimate the durable clinical benefit rate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Drug manufacturer decision to terminate development.&#xD;
  </why_stopped>
  <start_date type="Actual">October 13, 2020</start_date>
  <completion_date type="Actual">October 22, 2021</completion_date>
  <primary_completion_date type="Actual">October 22, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Dose-limiting Toxicities (DLTs)</measure>
    <time_frame>8 weeks</time_frame>
    <description>The primary outcome for this study is dose-limiting toxicities (DLTs) during the first 2 cycles of therapy. All grades per the Common Terminology Criteria for Adverse Events (CTCAE). DLT is defined as a related and clinically significant adverse event (AE), including missed doses due to a related AE.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Treatment Emergent Adverse Events (TEAE)</measure>
    <time_frame>From first dose to 30 days after the last dose of study drug (up to 94 days)</time_frame>
    <description>Treatment emergent adverse events (TEAEs) are defined as adverse events of any grade with initial onset or increasing in severity after the first dose of study treatment until 30 days after last dose of study drug. Pregnancy during the reporting period will be classified as a serious adverse event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Tumor Response Rate</measure>
    <time_frame>From enrollment to day of scan (up to 64 days)</time_frame>
    <description>Objective tumor response will be assessed as achieving a Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete Response (CR) or a Partial Response (PR). The outcome will be reported as the number of subjects that achieve an overall response (OR) to treatment, ie, CR or PR, within 18 months of starting treatment. RECIST criteria are:&#xD;
CR = Disappearance of all target lesions&#xD;
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions&#xD;
Overall Response (OR) = CR + PR&#xD;
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)&#xD;
Stable disease (SD) = Small changes that do not meet any of the above criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>up to 9 months</time_frame>
    <description>Progression free survival (PFS) means the participant remains alive without return or relapse of the tumor. The outcome is defined as the number of days to either progressive disease as defined per RECIST v1.1 or death. RECIST criteria are:&#xD;
CR = Disappearance of all target lesions&#xD;
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions&#xD;
Overall Response (OR) = CR + PR&#xD;
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)&#xD;
Stable disease (SD) = Small changes that do not meet any of the above criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate</measure>
    <time_frame>6 months</time_frame>
    <description>Clinical benefit (CB) is defined as achieving a Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete Response (CR) ; Partial Response (PR); or Stable Disease (SD). The outcome will be reported as the number of subjects that achieve CR, PR, or SD. RECIST criteria are:&#xD;
CR = Disappearance of all target lesions&#xD;
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions&#xD;
SD = Small changes that do not meet any of the above criteria&#xD;
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Breast Cancer</condition>
  <condition>HER2-negative Breast Cancer</condition>
  <condition>ER Positive Breast Cancer</condition>
  <condition>PR-Positive Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Cohort 1: Infigratinib (100mg) + Tamoxifen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In study part 1 (dose exploration), participants will receive up to infigratinib 100 mg. 100 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: Infigratinib (125mg) + Tamoxifen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In study part 1 (dose exploration), participants will receive up to infigratinib 125 mg. 125 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3: Infigratinib (75mg) + Tamoxifen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In study part 1 (dose exploration), participants will receive up to infigratinib 75 mg. 75 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Infigratinib</intervention_name>
    <description>Oral dose</description>
    <arm_group_label>Cohort 1: Infigratinib (100mg) + Tamoxifen</arm_group_label>
    <arm_group_label>Cohort 2: Infigratinib (125mg) + Tamoxifen</arm_group_label>
    <arm_group_label>Cohort 3: Infigratinib (75mg) + Tamoxifen</arm_group_label>
    <other_name>FGFR 1-3-Selective Tyrosine Kinase Inhibitor</other_name>
    <other_name>872511-34-7</other_name>
    <other_name>NVP-BGJ398</other_name>
    <other_name>BGJ-398</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tamoxifen</intervention_name>
    <description>Oral Dose</description>
    <arm_group_label>Cohort 1: Infigratinib (100mg) + Tamoxifen</arm_group_label>
    <arm_group_label>Cohort 2: Infigratinib (125mg) + Tamoxifen</arm_group_label>
    <arm_group_label>Cohort 3: Infigratinib (75mg) + Tamoxifen</arm_group_label>
    <other_name>Nolvadex</other_name>
    <other_name>Soltamox</other_name>
    <other_name>Apo-Tamox</other_name>
    <other_name>Tamofen</other_name>
    <other_name>Tamone</other_name>
    <other_name>ICI-46474</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omnipaque 350</intervention_name>
    <description>IV contrast agent</description>
    <arm_group_label>Cohort 1: Infigratinib (100mg) + Tamoxifen</arm_group_label>
    <arm_group_label>Cohort 2: Infigratinib (125mg) + Tamoxifen</arm_group_label>
    <arm_group_label>Cohort 3: Infigratinib (75mg) + Tamoxifen</arm_group_label>
    <other_name>Iohexol</other_name>
    <other_name>Hexopaque</other_name>
    <other_name>Nycodenz</other_name>
    <other_name>Exypaque</other_name>
    <other_name>Compound 545</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Iopamidol</intervention_name>
    <description>IV contrast agent</description>
    <arm_group_label>Cohort 1: Infigratinib (100mg) + Tamoxifen</arm_group_label>
    <arm_group_label>Cohort 2: Infigratinib (125mg) + Tamoxifen</arm_group_label>
    <arm_group_label>Cohort 3: Infigratinib (75mg) + Tamoxifen</arm_group_label>
    <other_name>Isovue 300</other_name>
    <other_name>Isovue 370</other_name>
    <other_name>Iopamiro</other_name>
    <other_name>Iopamiron</other_name>
    <other_name>Scanlux</other_name>
    <other_name>Niopam</other_name>
    <other_name>Jopamidol</other_name>
    <other_name>Solutrast</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Computed tomography (CT)</intervention_name>
    <description>Computed tomography (CT) to assess disease state using Iopamidol and/or Omnipaque 350.</description>
    <arm_group_label>Cohort 1: Infigratinib (100mg) + Tamoxifen</arm_group_label>
    <arm_group_label>Cohort 2: Infigratinib (125mg) + Tamoxifen</arm_group_label>
    <arm_group_label>Cohort 3: Infigratinib (75mg) + Tamoxifen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  History of biopsy proven ER positive and/or PR positive, HER2 negative breast cancer&#xD;
             and radiographic evidence of metastatic disease, or locally recurrent unresectable&#xD;
             disease. ER positivity and PR positivity are defined as ≥ 1% cells staining positive&#xD;
             by immunohistochemistry. HER2 negativity is defined by immunohistochemistry (IHC) or&#xD;
             Fluorescence in situ hybridization (FISH).&#xD;
&#xD;
          -  Cancer subtype: Predicted integrative subtype classification of IC2 or IC6 according&#xD;
             classifier on targeted sequencing data from FoundationOne.&#xD;
&#xD;
          -  Evaluable or measurable disease, by cohort. Cohort 1 only: Evaluable or measurable&#xD;
             disease, as defined by RECIST v1.1. Bone only disease is acceptable.&#xD;
&#xD;
        Cohort 2 only: Measurable disease, as defined by RECIST v1.1.&#xD;
&#xD;
          -  ≥ 18 years old&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) 0 to 2&#xD;
&#xD;
          -  Prior cancer therapy (except for endocrine therapy, denosumab, or bisphosphonates)&#xD;
             must be discontinued for 2 weeks prior to initiation of study drugs. Recovery from&#xD;
             adverse events of previous cancer therapies to baseline or Grade 1 except for alopecia&#xD;
             or stable Grade 2 neuropathy. Radiotherapy must also be completed at least 2 weeks&#xD;
             prior to initiation of study drugs&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1,000/mm3&#xD;
&#xD;
          -  Platelets ≥ 75,000/mm3&#xD;
&#xD;
          -  Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
          -  Total bilirubin ≤ 1.8 mg/dL (unless documented Gilbert's disease)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) &lt; 90 U/L&#xD;
&#xD;
          -  Estimated glomerular filtration rate (GFR) ≥ 45 mL/min&#xD;
&#xD;
          -  Phosphorus between 2.5 and 4.5 mg/dL, inclusive&#xD;
&#xD;
          -  Total corrected (for albumin) serum calcium between 8.5 and 10.5 mg/dL, inclusive&#xD;
&#xD;
          -  Amylase &lt; 200 U/L&#xD;
&#xD;
          -  Lipase &lt; 120 U/L&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
          -  Agrees to take sevelamer, if indicated, and has no contraindications to use of this&#xD;
             medication (that is: known hypersensitivity to sevelamer or component of the&#xD;
             formulation; bowel obstruction; active bowel mucosal injury such as ulcerative colitis&#xD;
             or gastrointestinal bleeding).&#xD;
&#xD;
          -  Agrees to follow low phosphate diet, if indicated&#xD;
&#xD;
          -  Able to swallow and retain oral medication&#xD;
&#xD;
          -  Women must be postmenopausal, defined as (at least one of):&#xD;
&#xD;
               -  ≥ 60 years of age;&#xD;
&#xD;
               -  amenorrhea for at least 24 months;&#xD;
&#xD;
               -  amenorrhea for at least 12 months with serum estradiol &lt; 20 pg/mL;&#xD;
&#xD;
               -  prior bilateral oophorectomy; OR&#xD;
&#xD;
               -  treatment with a luteinizing hormone (LH) releasing hormone agonist (such as&#xD;
                  goserelin acetate or leuprolide acetate) initiated at least 28 days prior to&#xD;
                  study enrollment.&#xD;
&#xD;
          -  Women being treated with a LH releasing agonist but who are otherwise of childbearing&#xD;
             potential (did not undergo total hysterectomy or bilateral tubal ligation at least 6&#xD;
             weeks before first dose of study drug) must have a negative pregnancy test within 7&#xD;
             days of the first dose of study drug.&#xD;
&#xD;
          -  Women who are being treated with a LH releasing agonist but are otherwise of&#xD;
             childbearing potential must agree to use barrier contraception or an intrauterine&#xD;
             device while taking study drug and for 3 months following their last dose of study&#xD;
             drug. Alternatively, total abstinence is acceptable if preferred by the subject.&#xD;
&#xD;
          -  Sexually active men must agree to use a condom during intercourse while taking drug&#xD;
             and for 3 months after the last dose of the study drug and should not father a child&#xD;
             during this period. A condom is required to be used also by vasectomized men as well&#xD;
             as during intercourse with a male partner to prevent delivery of the drug via seminal&#xD;
             fluid.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of another primary malignancy within 3 years except adequately treated in situ&#xD;
             carcinoma of the cervix or non melanoma carcinoma of the skin or any other curatively&#xD;
             treated malignancy that is not expected to require treatment for recurrence during the&#xD;
             course of the study.&#xD;
&#xD;
          -  Neurologic symptoms related to central nervous system metastases requiring increasing&#xD;
             doses of corticosteroids. Note that subjects with central nervous system metastases&#xD;
             are eligible if they are on a stable corticosteroid dose for at least 2 weeks&#xD;
             preceding study entry.&#xD;
&#xD;
          -  Current evidence of corneal or retinal disorder/keratopathy including, but not limited&#xD;
             to, bullous/band keratopathy, corneal abrasion, inflammation/ulceration,&#xD;
             keratoconjunctivitis, confirmed by ophthalmologic examination. Subjects with&#xD;
             asymptomatic ophthalmologic conditions assessed by the investigator to pose minimal&#xD;
             risk for study participation may be enrolled in the study.&#xD;
&#xD;
          -  Current evidence of extensive tissue calcification including, but not limited to, the&#xD;
             soft tissue, kidneys, intestine, myocardium, and lung with the exception of calcified&#xD;
             lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary&#xD;
             calcification.&#xD;
&#xD;
          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly&#xD;
             alter the absorption of oral infigratinib (eg, ulcerative diseases, uncontrolled&#xD;
             nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).&#xD;
&#xD;
          -  Current evidence of endocrine alterations of calcium/phosphate homeostasis, eg,&#xD;
             parathyroid disorders, history of parathyroidectomy, tumor lysis, or tumoral&#xD;
             calcinosis.&#xD;
&#xD;
          -  Currently receiving or planning during study participation to receive treatment with&#xD;
             agents that are known strong inducers or inhibitors of CYP3A4 and medications which&#xD;
             increase serum phosphorus and/or calcium concentration. Subjects are not permitted to&#xD;
             receive enzyme inducing anti epileptic drugs, including carbamazepine, phenytoin,&#xD;
             phenobarbital, and primidone. See Appendix B for a list of prohibited concomitant&#xD;
             medications and supplements.&#xD;
&#xD;
          -  Has consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star&#xD;
             fruits, pomelos, Seville oranges, or products containing juice of these fruits within&#xD;
             7 days prior to first dose of study drug.&#xD;
&#xD;
          -  Have used amiodarone within 90 days prior to first dose of study drug.&#xD;
&#xD;
          -  Has used medications known to prolong the QT interval and/or are associated with a&#xD;
             risk of Torsades de Pointes (TdP) 7 days prior to first dose of study drug. See&#xD;
             Appendix B for a list of prohibited concomitant medications and supplements.&#xD;
&#xD;
          -  Has used calcium or vitamin D within 3 days prior to first dose of study drug. Calcium&#xD;
             supplementation may subsequently be used as clinically indicated (for hypocalcemia) on&#xD;
             study.&#xD;
&#xD;
          -  Have clinically significant cardiac disease including any of the following:&#xD;
&#xD;
               1. Congestive heart failure requiring treatment (New York Heart Association Grade ≥&#xD;
                  2), left ventricular ejection fraction (LVEF) &lt; 50% or local lower limit of&#xD;
                  normal as determined by multiple gated acquisition (MUGA) scan or echocardiogram&#xD;
                  (ECHO), or uncontrolled hypertension (refer to the European Society of Cardiology&#xD;
                  and European Society of Hypertension guidelines [Williams et al., 2018])&#xD;
&#xD;
               2. Presence of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade ≥ 2&#xD;
                  ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction&#xD;
                  abnormality&#xD;
&#xD;
               3. Unstable angina pectoris or acute myocardial infarction ≤ 3 months prior to first&#xD;
                  dose of study drug&#xD;
&#xD;
               4. Corrected QT interval Fredericia (QTcF) &gt; 470 msec (males and females). Note: If&#xD;
                  the QTcF is &gt; 470 msec in the first electrocardiogram (ECG), a total of 3 ECGs&#xD;
                  separated by at least 5 minutes should be performed. If the average of these 3&#xD;
                  consecutive results for QTcF is ≤ 470 msec, the subject meets eligibility in this&#xD;
                  regard.&#xD;
&#xD;
               5. Known history of congenital long QT syndrome&#xD;
&#xD;
          -  Have had a recent (≤ 3 months) transient ischemic attack or stroke.&#xD;
&#xD;
          -  Pregnant or nursing woman.&#xD;
&#xD;
               -  All subject files must include supporting documentation to confirm subject&#xD;
                  eligibility. The method of confirmation can include, but is not limited to,&#xD;
                  laboratory test results, radiology test results, subject self report, and medical&#xD;
                  record review.&#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>Jennifer Lee Caswell-Jin</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford Universiy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 5, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <results_first_submitted>April 4, 2023</results_first_submitted>
  <results_first_submitted_qc>May 30, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 1, 2023</results_first_posted>
  <disposition_first_submitted>October 21, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>October 21, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">October 25, 2022</disposition_first_posted>
  <last_update_submitted>May 30, 2023</last_update_submitted>
  <last_update_submitted_qc>May 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Jennifer Lee Caswell-Jin</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine (Oncology)</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tamoxifen</mesh_term>
    <mesh_term>Infigratinib</mesh_term>
    <mesh_term>Tyrosine Protein Kinase Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 11, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT04504331/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 11, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT04504331/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Enrollment was closed before any participants were enrolled in Cohort 3 (Infigratinib (75 mg) + Tamoxifen).</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1: Infigratinib (100mg) + Tamoxifen</title>
          <description>In study part 1 (dose exploration), participants receive infigratinib up to 100 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2: Infigratinib (125mg) + Tamoxifen</title>
          <description>In study part 1 (dose exploration), participants receive infigratinib up to 125 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen</description>
        </group>
        <group group_id="P3">
          <title>Cohort 3: Infigratinib (75mg) + Tamoxifen</title>
          <description>In study part 1 (dose exploration), participants receive infigratinib up to 75 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Dose Level 1 (up to 18 28-day Cycles+FU)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed at Least 6 Treatment Cycles</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Dose Level 2 (up to 18 28-day Cycles+FU)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed at Least 6 Treatment Cycles</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1: Infigratinib (100mg) + Tamoxifen</title>
          <description>In study part 1 (dose exploration), participants receive infigratinib up to 100 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2: Infigratinib (125mg) + Tamoxifen</title>
          <description>In study part 1 (dose exploration), participants receive infigratinib up to 125 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="4"/>
          </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.2" spread="9.6"/>
                    <measurement group_id="B2" value="38.5" spread="NA">Not calculable for a single value</measurement>
                    <measurement group_id="B3" value="53.9" spread="13.0"/>
                  </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="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Dose-limiting Toxicities (DLTs)</title>
        <description>The primary outcome for this study is dose-limiting toxicities (DLTs) during the first 2 cycles of therapy. All grades per the Common Terminology Criteria for Adverse Events (CTCAE). DLT is defined as a related and clinically significant adverse event (AE), including missed doses due to a related AE.</description>
        <time_frame>8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Infigratinib (100mg) + Tamoxifen</title>
            <description>In study part 1 (dose exploration), participants receive infigratinib up to 100 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Infigratinib (125mg) + Tamoxifen</title>
            <description>In study part 1 (dose exploration), participants receive infigratinib up to 125 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Dose-limiting Toxicities (DLTs)</title>
          <description>The primary outcome for this study is dose-limiting toxicities (DLTs) during the first 2 cycles of therapy. All grades per the Common Terminology Criteria for Adverse Events (CTCAE). DLT is defined as a related and clinically significant adverse event (AE), including missed doses due to a related AE.</description>
          <units>DLTs</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Treatment Emergent Adverse Events (TEAE)</title>
        <description>Treatment emergent adverse events (TEAEs) are defined as adverse events of any grade with initial onset or increasing in severity after the first dose of study treatment until 30 days after last dose of study drug. Pregnancy during the reporting period will be classified as a serious adverse event.</description>
        <time_frame>From first dose to 30 days after the last dose of study drug (up to 94 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Infigratinib (100mg) + Tamoxifen</title>
            <description>In study part 1 (dose exploration), participants receive infigratinib up to 100 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Infigratinib (125mg) + Tamoxifen</title>
            <description>In study part 1 (dose exploration), participants receive infigratinib up to 125 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment Emergent Adverse Events (TEAE)</title>
          <description>Treatment emergent adverse events (TEAEs) are defined as adverse events of any grade with initial onset or increasing in severity after the first dose of study treatment until 30 days after last dose of study drug. Pregnancy during the reporting period will be classified as a serious adverse event.</description>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Tumor Response Rate</title>
        <description>Objective tumor response will be assessed as achieving a Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete Response (CR) or a Partial Response (PR). The outcome will be reported as the number of subjects that achieve an overall response (OR) to treatment, ie, CR or PR, within 18 months of starting treatment. RECIST criteria are:&#xD;
CR = Disappearance of all target lesions&#xD;
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions&#xD;
Overall Response (OR) = CR + PR&#xD;
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)&#xD;
Stable disease (SD) = Small changes that do not meet any of the above criteria</description>
        <time_frame>From enrollment to day of scan (up to 64 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Infigratinib (100mg) + Tamoxifen</title>
            <description>In study part 1 (dose exploration), participants receive infigratinib up to 100 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Infigratinib (125mg) + Tamoxifen</title>
            <description>In study part 1 (dose exploration), participants receive infigratinib up to 125 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Tumor Response Rate</title>
          <description>Objective tumor response will be assessed as achieving a Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete Response (CR) or a Partial Response (PR). The outcome will be reported as the number of subjects that achieve an overall response (OR) to treatment, ie, CR or PR, within 18 months of starting treatment. RECIST criteria are:&#xD;
CR = Disappearance of all target lesions&#xD;
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions&#xD;
Overall Response (OR) = CR + PR&#xD;
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)&#xD;
Stable disease (SD) = Small changes that do not meet any of the above criteria</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>CR</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>PR</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>OR (CR + PR)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>PD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>SD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>Progression free survival (PFS) means the participant remains alive without return or relapse of the tumor. The outcome is defined as the number of days to either progressive disease as defined per RECIST v1.1 or death. RECIST criteria are:&#xD;
CR = Disappearance of all target lesions&#xD;
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions&#xD;
Overall Response (OR) = CR + PR&#xD;
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)&#xD;
Stable disease (SD) = Small changes that do not meet any of the above criteria</description>
        <time_frame>up to 9 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Infigratinib (100mg) + Tamoxifen</title>
            <description>In study part 1 (dose exploration), participants receive infigratinib up to 100 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Infigratinib (125mg) + Tamoxifen</title>
            <description>In study part 1 (dose exploration), participants receive infigratinib up to 125 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>Progression free survival (PFS) means the participant remains alive without return or relapse of the tumor. The outcome is defined as the number of days to either progressive disease as defined per RECIST v1.1 or death. RECIST criteria are:&#xD;
CR = Disappearance of all target lesions&#xD;
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions&#xD;
Overall Response (OR) = CR + PR&#xD;
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)&#xD;
Stable disease (SD) = Small changes that do not meet any of the above criteria</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61" spread="5.3"/>
                    <measurement group_id="O2" value="NA">Not evaluable due to insufficient number of events</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Rate</title>
        <description>Clinical benefit (CB) is defined as achieving a Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete Response (CR) ; Partial Response (PR); or Stable Disease (SD). The outcome will be reported as the number of subjects that achieve CR, PR, or SD. RECIST criteria are:&#xD;
CR = Disappearance of all target lesions&#xD;
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions&#xD;
SD = Small changes that do not meet any of the above criteria&#xD;
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)</description>
        <time_frame>6 months</time_frame>
        <population>Participants who completed at least 6 treatment cycles are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Infigratinib (100mg) + Tamoxifen</title>
            <description>In study part 1 (dose exploration), participants receive infigratinib up to 100 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Infigratinib (125mg) + Tamoxifen</title>
            <description>In study part 1 (dose exploration), participants receive infigratinib up to 125 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate</title>
          <description>Clinical benefit (CB) is defined as achieving a Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete Response (CR) ; Partial Response (PR); or Stable Disease (SD). The outcome will be reported as the number of subjects that achieve CR, PR, or SD. RECIST criteria are:&#xD;
CR = Disappearance of all target lesions&#xD;
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions&#xD;
SD = Small changes that do not meet any of the above criteria&#xD;
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)</description>
          <population>Participants who completed at least 6 treatment cycles are included in the analysis.</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="3"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CB (CR + PR +SD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 9 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1: Infigratinib (100mg) + Tamoxifen</title>
          <description>In study part 1 (dose exploration), participants receive infigratinib up to 100 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2: Infigratinib (125mg) + Tamoxifen</title>
          <description>In study part 1 (dose exploration), participants receive infigratinib up to 125 mg administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen</description>
        </group>
      </group_list>
      <serious_events>
        <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="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrioventricular block complete</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Retinopathy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry Eye</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Other - corneal endothelial cell count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Immune system disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperphosphataemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypophosphtaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Myalgia of lower extremities</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Other - pulling sensation in uterus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Other - yeast infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry nose</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Other - Eyelash thickening</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nail discoloration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Retinopathy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </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>Jennifer Lee Caswell-Jin, MD</name_or_title>
      <organization>Stanford Medicine at Stanford University</organization>
      <phone>1-310-332-6541</phone>
      <email>caswell@stanford.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/NCT04504331
org study id: IRB-53650
secondary id: BRS0113
secondary id: K08CA252457
secondary id: NCI-2020-13784
nct id: NCT04504331
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of the study is identify the dose(s) of infigratinib to use in combination with
      tamoxifen to treat patients with a particular type of advanced breast cancer (hormone
      receptor-positive, HER2-negative, FGFR-altered breast cancer)
Primary Objective: Determine the maximum (no greater than 125 mg) dose of infigratinib used
      in combination with the FDA-approved dose and schedule of tamoxifen (Cohort 1) in terms of
      the number of dose-limiting toxicities observed in the first 2 cycles of therapy in subjects
      with hormone receptor-positive, HER2-negative advanced breast cancer.

      Secondary Objective:

        -  Estimate the incidence of treatment-emergent adverse events (serious and non-serious).

        -  Estimate the objective tumor response rate (ORR) in subjects with measurable disease.

        -  Estimate the progression-free survival (PFS).

        -  Estimate the durable clinical benefit rate.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Dose-limiting Toxicities (DLTs)
time frame: 8 weeks
description: The primary outcome for this study is dose-limiting toxicities (DLTs) during the first 2 cycles of therapy. All grades per the Common Terminology Criteria for Adverse Events (CTCAE). DLT is defined as a related and clinically significant adverse event (AE), including missed doses due to a related AE.
measure: Number of Treatment Emergent Adverse Events (TEAE)
time frame: From first dose to 30 days after the last dose of study drug (up to 94 days)
description: Treatment emergent adverse events (TEAEs) are defined as adverse events of any grade with initial onset or increasing in severity after the first dose of study treatment until 30 days after last dose of study drug. Pregnancy during the reporting period will be classified as a serious adverse event.
measure: Objective Tumor Response Rate
time frame: From enrollment to day of scan (up to 64 days)
description: Objective tumor response will be assessed as achieving a Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete Response (CR) or a Partial Response (PR). The outcome will be reported as the number of subjects that achieve an overall response (OR) to treatment, ie, CR or PR, within 18 months of starting treatment. RECIST criteria are:
CR = Disappearance of all target lesions
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions
Overall Response (OR) = CR + PR
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)
Stable disease (SD) = Small changes that do not meet any of the above criteria
measure: Progression-free Survival (PFS)
time frame: up to 9 months
description: Progression free survival (PFS) means the participant remains alive without return or relapse of the tumor. The outcome is defined as the number of days to either progressive disease as defined per RECIST v1.1 or death. RECIST criteria are:
CR = Disappearance of all target lesions
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions
Overall Response (OR) = CR + PR
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)
Stable disease (SD) = Small changes that do not meet any of the above criteria
measure: Clinical Benefit Rate
time frame: 6 months
description: Clinical benefit (CB) is defined as achieving a Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete Response (CR) ; Partial Response (PR); or Stable Disease (SD). The outcome will be reported as the number of subjects that achieve CR, PR, or SD. RECIST criteria are:
CR = Disappearance of all target lesions
PR = ≥ 30% decrease in the sum of the longest diameter of target lesions
SD = Small changes that do not meet any of the above criteria
Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)
arm group label: Cohort 1: Infigratinib (100mg) + Tamoxifen
arm group type: Experimental
description: In study part 1 (dose exploration), participants will receive up to infigratinib 100 mg. 100 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen
arm group label: Cohort 2: Infigratinib (125mg) + Tamoxifen
arm group type: Experimental
description: In study part 1 (dose exploration), participants will receive up to infigratinib 125 mg. 125 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen
arm group label: Cohort 3: Infigratinib (75mg) + Tamoxifen
arm group type: Experimental
description: In study part 1 (dose exploration), participants will receive up to infigratinib 75 mg. 75 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen
intervention type: Drug
intervention name: Infigratinib
description: Oral dose
arm group label: Cohort 1: Infigratinib (100mg) + Tamoxifen
arm group label: Cohort 2: Infigratinib (125mg) + Tamoxifen
arm group label: Cohort 3: Infigratinib (75mg) + Tamoxifen
other name: FGFR 1-3-Selective Tyrosine Kinase Inhibitor
other name: 872511-34-7
other name: NVP-BGJ398
other name: BGJ-398
intervention type: Drug
intervention name: Tamoxifen
description: Oral Dose
arm group label: Cohort 1: Infigratinib (100mg) + Tamoxifen
arm group label: Cohort 2: Infigratinib (125mg) + Tamoxifen
arm group label: Cohort 3: Infigratinib (75mg) + Tamoxifen
other name: Nolvadex
other name: Soltamox
other name: Apo-Tamox
other name: Tamofen
other name: Tamone
other name: ICI-46474
intervention type: Drug
intervention name: Omnipaque 350
description: IV contrast agent
arm group label: Cohort 1: Infigratinib (100mg) + Tamoxifen
arm group label: Cohort 2: Infigratinib (125mg) + Tamoxifen
arm group label: Cohort 3: Infigratinib (75mg) + Tamoxifen
other name: Iohexol
other name: Hexopaque
other name: Nycodenz
other name: Exypaque
other name: Compound 545
intervention type: Drug
intervention name: Iopamidol
description: IV contrast agent
arm group label: Cohort 1: Infigratinib (100mg) + Tamoxifen
arm group label: Cohort 2: Infigratinib (125mg) + Tamoxifen
arm group label: Cohort 3: Infigratinib (75mg) + Tamoxifen
other name: Isovue 300
other name: Isovue 370
other name: Iopamiro
other name: Iopamiron
other name: Scanlux
other name: Niopam
other name: Jopamidol
other name: Solutrast
intervention type: Diagnostic Test
intervention name: Computed tomography (CT)
description: Computed tomography (CT) to assess disease state using Iopamidol and/or Omnipaque 350.
arm group label: Cohort 1: Infigratinib (100mg) + Tamoxifen
arm group label: Cohort 2: Infigratinib (125mg) + Tamoxifen
arm group label: Cohort 3: Infigratinib (75mg) + Tamoxifen
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer Lee Caswell-Jin
role: Principal Investigator
affiliation: Stanford Universiy
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Stanford University
investigator full name: Jennifer Lee Caswell-Jin
investigator title: Assistant Professor of Medicine (Oncology)
mesh term: Breast Neoplasms
mesh term: Tamoxifen
mesh term: Infigratinib
mesh term: Tyrosine Protein Kinase Inhibitors
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 