<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/NCT03775525</url>
  </required_header>
  <id_info>
    <org_study_id>GEN-602-CT-101</org_study_id>
    <nct_id>NCT03775525</nct_id>
  </id_info>
  <brief_title>Study Evaluating GZ17-6.02 in Patients With Advanced Solid Tumors or in Combination With Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer</brief_title>
  <acronym>GEN602</acronym>
  <official_title>A Phase I/Ib, Multicenter, Open-label, Dose-Escalation, Safety, Pharmacodynamic and Pharmacokinetic Study of GZ17-6.02 Monotherapy and in Combination With Capecitabine, Given Orally on a Daily Schedule in Patients With Advanced Solid Tumors or Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genzada Pharmaceuticals USA, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Translational Drug Development</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Genzada Pharmaceuticals USA, Inc.</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>
      This Phase I/Ib study is a Multicenter, Open-label, Dose-Escalation, Safety, Pharmacodynamic&#xD;
      and Pharmacokinetic Study of GZ17-6.02 Monotherapy and in Combination with Capecitabine,&#xD;
      Given Orally on a Daily Schedule in Patients with Advanced Solid Tumors or Lymphoma&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will evaluate the safety, pharmacokinetics, and pharmacodynamic effects of a novel&#xD;
      anti-cancer drug, GZ17-6.02 administered to patients with advanced solid tumors or lymphoma,&#xD;
      which have progressed after receiving standard/approved therapy or where there is no approved&#xD;
      therapy.&#xD;
&#xD;
      This study will determine the maximum tolerated dose (MTD) and the dose limiting toxicities&#xD;
      (DLT) of GZ17-6.02 monotherapy and in combination with standard-of-care oncology treatments&#xD;
      and to establish the dose of GZ17-6.02 recommended for future monotherapy and combination&#xD;
      therapies phase II oncology clinical studies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">May 2023</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>maximum tolerated dose (MTD)</measure>
    <time_frame>18 months</time_frame>
    <description>As assessed by CTCAE v4.03</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended dose of GZ17-6.02 for future phase II clinical studies</measure>
    <time_frame>18 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose-limiting toxicity</measure>
    <time_frame>18 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Antitumor effect</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under Concentration Curve</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax)</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Plasma Concentration (Tmax)</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Phase Half-Life (t1/2)</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Body Clearance (CL/F)</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution (Vd/F)</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">127</enrollment>
  <condition>Advanced Cancer</condition>
  <condition>Gastric Cancer</condition>
  <condition>Breast Cancer</condition>
  <condition>Pancreatic Cancer</condition>
  <condition>Prostate Cancer Metastatic</condition>
  <condition>Colo-rectal Cancer</condition>
  <condition>Solid Tumor</condition>
  <condition>Solid Carcinoma</condition>
  <condition>Solid Carcinoma of Stomach</condition>
  <condition>Cancer of Stomach</condition>
  <condition>Lymphoma</condition>
  <condition>Sarcoma</condition>
  <condition>Cutaneous T Cell Lymphoma</condition>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Basal Cell Carcinoma</condition>
  <condition>Cutaneous T-cell Lymphoma</condition>
  <condition>Cutaneous Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Experimental: monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GZ17-6.02 given orally on a daily x 28 day schedule. This will be a dose escalation study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 825 mg/m2 orally twice daily for 14 days x 21 day schedule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 850 mg/m2 orally twice daily for 14 days x 21 day schedule.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GZ17-6.02</intervention_name>
    <description>Super enhancer Inhibition</description>
    <arm_group_label>Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer</arm_group_label>
    <arm_group_label>Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer</arm_group_label>
    <arm_group_label>Experimental: monotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>antimetabolite</description>
    <arm_group_label>Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer</arm_group_label>
    <arm_group_label>Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer</arm_group_label>
    <other_name>Xeloda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        General Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a pathologically confirmed diagnosis of advanced solid tumors or&#xD;
             lymphoma.&#xD;
&#xD;
          -  Tumor progression after receiving standard/approved therapies which may include&#xD;
             chemotherapy, targeted agents, radio-immuno conjugates, check point inhibitors, where&#xD;
             there is no approved therapy; or the patient is intolerant of standard of care or the&#xD;
             patient declines standard of care treatment&#xD;
&#xD;
          -  One or more metastatic tumors measurable, or evaluable, per RECIST v1.1 Criteria for&#xD;
             solid tumors and Lugano Criteria for lymphoma&#xD;
&#xD;
          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1&#xD;
&#xD;
          -  Life expectancy of at least 3 months&#xD;
&#xD;
          -  Age 18 years&#xD;
&#xD;
          -  Signed, written IRB-approved informed consent&#xD;
&#xD;
          -  A negative pregnancy test (if female)&#xD;
&#xD;
          -  Acceptable liver function:&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 times upper limit of normal&#xD;
&#xD;
               -  AST (SGOT), ALT (SGPT) and Alkaline phosphatase ≤ 2.5 times upper limit of normal&#xD;
                  (if liver metastases are present, then ≤ 5 x ULN is allowed)&#xD;
&#xD;
          -  Acceptable renal function:&#xD;
&#xD;
             o Serum creatinine ≤ 1.5 times institutional ULN, OR calculated creatinine clearance ≥&#xD;
             60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.&#xD;
&#xD;
          -  Acceptable hematologic status:&#xD;
&#xD;
               -  Granulocyte ≥ 1500 cells/mm3&#xD;
&#xD;
               -  Platelet count ≥ 100,000 (plt/mm3)&#xD;
&#xD;
               -  Hemoglobin ≥ 9 g/dL&#xD;
&#xD;
          -  Urinalysis:&#xD;
&#xD;
             o No clinically significant abnormalities&#xD;
&#xD;
          -  Acceptable coagulation status (for patients on warfarin or other anti-coagulants, a&#xD;
             PT/PTT considered by the PI as therapeutically appropriate will be allowed):&#xD;
&#xD;
               -  PT within ≤ 1.5 times normal limits&#xD;
&#xD;
               -  PTT within ≤ 1.5 times normal limits&#xD;
&#xD;
          -  For men and women of child-producing potential, the use of effective contraceptive&#xD;
             methods during the study&#xD;
&#xD;
          -  Fasting glucose ≤ 180 mg/dL&#xD;
&#xD;
          -  Albumin ≥ 3.0 g/dL within seven days of initiating protocol treatment&#xD;
&#xD;
        For patients in the GZ17-6.02 plus capecitabine Phase 1b Expansion Cohort 2 (metastatic&#xD;
        breast cancer):&#xD;
&#xD;
          -  Pathologically confirmed diagnosis of HER2-negative and Hormone Receptor (HR)&#xD;
             (estrogen receptor [ER] and/or progesterone receptor)-positive metastatic breast&#xD;
             cancer;&#xD;
&#xD;
          -  Had ≤ 1 prior treatment (not including neoadjuvant or adjuvant treatment);&#xD;
&#xD;
          -  Are naïve to capecitabine but not necessarily to fluorouracil (5 FU);&#xD;
&#xD;
          -  Eligible for standard-of-care treatment with capecitabine monotherapy.&#xD;
&#xD;
          -  Patients in Expansion Cohort 2 with bone-only metastatic disease must have one or more&#xD;
             lytic or a mixed lytic-blastic lesions that can be assessed by computed tomography&#xD;
             (CT) scan or magnetic resonance imaging (MRI).&#xD;
&#xD;
        For patients in GZ17-6.02 plus capecitabine Phase 1b Expansion Cohort 3 (metastatic&#xD;
        colorectal cancer):&#xD;
&#xD;
          -  Pathologically confirmed diagnosis of metastatic colorectal cancer;&#xD;
&#xD;
          -  Had ≤ 2 prior treatments (not including neoadjuvant or adjuvant treatment);&#xD;
&#xD;
          -  Are naïve to capecitabine but not necessarily to 5 FU;&#xD;
&#xD;
          -  Eligible for standard-of-care treatment with capecitabine monotherapy.&#xD;
&#xD;
        General Exclusion Criteria: (All patients, unless otherwise specified):&#xD;
&#xD;
          -  New York Heart Association Class III or IV, cardiac disease, myocardial infarction&#xD;
             within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.&#xD;
&#xD;
          -  Currently taking MAOIs&#xD;
&#xD;
          -  Baseline QTc exceeding 450 msec in males, 470 msec in females (using the Fridericia's&#xD;
             formula) and/or patients receiving class 1A or class III antiarrhythmic agents;&#xD;
&#xD;
          -  Known active, uncontrolled bacterial, viral, or fungal infections requiring systemic&#xD;
             therapy;&#xD;
&#xD;
          -  Pregnant or nursing women.&#xD;
&#xD;
          -  NOTE: Women of child-bearing potential and men must agree to use adequate&#xD;
             contraception (hormonal or barrier method of birth control; or abstinence) prior to&#xD;
             study entry and for the duration of study participation. Should a woman become&#xD;
             pregnant or suspect she is pregnant while participating in this study, she should&#xD;
             inform her treating physician immediately.&#xD;
&#xD;
          -  Treatment with radiation therapy or surgery within 1 month prior to study entry.&#xD;
&#xD;
          -  Treatment with chemotherapy, targeted therapeutics (e.g. tyrosine kinase inhibitors,&#xD;
             therapeutic antibodies, etc), or investigational therapies within 1 month, or 5&#xD;
             half-lives (whichever is shorter), prior to study entry (6 weeks for nitrosoureas or&#xD;
             mitomycin C). For radiopharmaceuticals, within 1 month unless hematopoietic recovery&#xD;
             has not returned to pretreatment baseline;&#xD;
&#xD;
          -  Unwillingness or inability to comply with procedures required in this protocol;&#xD;
&#xD;
          -  Known active infection with HIV, HTLV-1, hepatitis B, hepatitis C or other chronic&#xD;
             viral infections that could interfere with the interpretation of study data;&#xD;
&#xD;
          -  Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other&#xD;
             conditions) that could compromise protocol objectives in the opinion of the&#xD;
             investigator and/or the sponsor.&#xD;
&#xD;
          -  Patients who are currently receiving any other investigational agent;&#xD;
&#xD;
          -  Primary Central Nervous System (CNS) malignancies;&#xD;
&#xD;
          -  Active CNS metastases requiring treatment or radiotherapy, or which have not been&#xD;
             confirmed stable on radiographic imaging for ≥30 days prior to C1D1;&#xD;
&#xD;
          -  Patients requiring steroids for neurological signs and symptom stabilization.&#xD;
&#xD;
          -  Patients who are unable to successfully discontinue all prohibited medications listed&#xD;
             in Appendix 6;&#xD;
&#xD;
          -  Patients must not have received a transfusion (platelets or red blood cells) ≤ 2 weeks&#xD;
             prior to initiating protocol therapy.&#xD;
&#xD;
        For patients in the GZ17-6.02 monotherapy Dose Escalation Cohort and patients in Expansion&#xD;
        Cohort 1:&#xD;
&#xD;
        • Patients with cow's milk allergy or with galactosemia&#xD;
&#xD;
        Phase 1b Expansion Cohort 2 (metastatic breast cancer) and Expansion Cohort 3 (metastatic&#xD;
        colorectal cancer):&#xD;
&#xD;
          -  Any history of coronary artery disease is exclusionary; New York Heart Association&#xD;
             Class III or IV, cardiac disease, myocardial infarction within the past 6 months,&#xD;
             unstable arrhythmia, or evidence of ischemia on the ECG.&#xD;
&#xD;
          -  Any conditions or medications that are contraindicated with capecitabine dosing;&#xD;
&#xD;
          -  Dihydropyrimidine dehydrogenase (DPD) deficiency;&#xD;
&#xD;
          -  Known sensitivity to capecitabine or any of its components or to 5-FU ;&#xD;
&#xD;
          -  Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other&#xD;
             conditions) that could compromise protocol objectives in the opinion of the&#xD;
             investigator and/or the sponsor&#xD;
&#xD;
             o This includes prior gastrointestinal surgery that would interfere with the oral drug&#xD;
             absorption.&#xD;
&#xD;
          -  Malignancy other than metastatic breast cancer (Expansion Cohort 2) or metastatic&#xD;
             colorectal cancer (Expansion Cohort 3) that required therapy within the preceding 5&#xD;
             years, other than adequately treated:&#xD;
&#xD;
               -  non-melanoma skin cancer or in situ cancer;&#xD;
&#xD;
               -  another cancer that has a very low risk of interfering with the safety or&#xD;
                  efficacy endpoints of the study, must be approved by the Sponsor medical team.&#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>Kathryn Gazarik</last_name>
    <role>Study Director</role>
    <affiliation>Translational Drug Development</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>HonorHealth Research Institute</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Clinic Foundation</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Charles A. Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <last_update_submitted>December 22, 2022</last_update_submitted>
  <last_update_submitted_qc>December 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 23, 2022</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>Lymphoma</mesh_term>
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Stomach Neoplasms</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Carcinoma, Basal Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Cutaneous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03775525
org study id: GEN-602-CT-101
nct id: NCT03775525
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This Phase I/Ib study is a Multicenter, Open-label, Dose-Escalation, Safety, Pharmacodynamic
      and Pharmacokinetic Study of GZ17-6.02 Monotherapy and in Combination with Capecitabine,
      Given Orally on a Daily Schedule in Patients with Advanced Solid Tumors or Lymphoma
This study will evaluate the safety, pharmacokinetics, and pharmacodynamic effects of a novel
      anti-cancer drug, GZ17-6.02 administered to patients with advanced solid tumors or lymphoma,
      which have progressed after receiving standard/approved therapy or where there is no approved
      therapy.

      This study will determine the maximum tolerated dose (MTD) and the dose limiting toxicities
      (DLT) of GZ17-6.02 monotherapy and in combination with standard-of-care oncology treatments
      and to establish the dose of GZ17-6.02 recommended for future monotherapy and combination
      therapies phase II oncology clinical studies.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: maximum tolerated dose (MTD)
time frame: 18 months
description: As assessed by CTCAE v4.03
measure: Recommended dose of GZ17-6.02 for future phase II clinical studies
time frame: 18 months
measure: Dose-limiting toxicity
time frame: 18 months
measure: Antitumor effect
time frame: 18 months
measure: Area Under Concentration Curve
time frame: 18 months
measure: Maximum Plasma Concentration (Cmax)
time frame: 18 months
measure: Time to Maximum Plasma Concentration (Tmax)
time frame: 18 months
measure: Terminal Phase Half-Life (t1/2)
time frame: 18 months
measure: Total Body Clearance (CL/F)
time frame: 18 months
measure: Apparent Volume of Distribution (Vd/F)
time frame: 18 months
arm group label: Experimental: monotherapy
arm group type: Experimental
description: GZ17-6.02 given orally on a daily x 28 day schedule. This will be a dose escalation study.
arm group label: Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer
arm group type: Experimental
description: GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 825 mg/m2 orally twice daily for 14 days x 21 day schedule.
arm group label: Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer
arm group type: Experimental
description: GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 850 mg/m2 orally twice daily for 14 days x 21 day schedule.
intervention type: Drug
intervention name: GZ17-6.02
description: Super enhancer Inhibition
arm group label: Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer
arm group label: Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer
arm group label: Experimental: monotherapy
intervention type: Drug
intervention name: Capecitabine
description: antimetabolite
arm group label: Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer
arm group label: Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer
other name: Xeloda
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kathryn Gazarik
role: Study Director
affiliation: Translational Drug Development
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Carcinoma
mesh term: Breast Neoplasms
mesh term: Carcinoma, Squamous Cell
mesh term: Stomach Neoplasms
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Carcinoma, Basal Cell
mesh term: Lymphoma, T-Cell, Cutaneous
mesh term: Capecitabine
sharing ipd: No