xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05993455</url>
    </required_header>
    <id_info>
      <org_study_id>KRAUS</org_study_id>
      <nct_id>NCT05993455</nct_id>
    </id_info>
    <brief_title>A Phase 2 Basket Trial in Which Patients With Advanced Solid Tumors Carrying the KRAS G12C mUtation Receive Treatment With a Combination of Sotorasib and Panitumumab</brief_title>
    <official_title>A Phase 2 Basket Trial in Which Patients With Advanced Solid Tumors Carrying the KRAS G12C mUtation Receive Treatment With a Combination of Sotorasib and Panitumumab (KRAUS)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Korea University Anam Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Korea University Anam Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</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>
        Kirsten rat sarcoma (KRAS) mutation is one of the most common genetic mutations associated&#xD;
        with tumor development in various human cancers, including pancreatic cancer, non-small cell&#xD;
        lung cancer, and colorectal cancer. Previous studies have shown that KRAS mutations are&#xD;
        present in approximately 70% of pancreatic cancer patients, 35% of colorectal cancer&#xD;
        patients, 20% of non-small cell lung cancer patients, and 15% of cervical cancer patients.&#xD;
        Patients with KRAS mutations generally have a shorter overall survival and increased&#xD;
        resistance to treatment compared to wild-type tumors. KRAS mutations have been known for&#xD;
        decades, but they have been considered &quot;undruggable&quot; as effective therapies targeting them&#xD;
        were lacking.&#xD;
  &#xD;
        Preclinical studies focusing on colorectal and non-small cell lung cancer cell lines have&#xD;
        suggested that colorectal cancer cell lines exhibit a stronger response to EGFR signaling and&#xD;
        activation of multiple RTKs (Receptor Tyrosine Kinases) than non-small cell lung cancer cell&#xD;
        lines. As a result, they show poorer responses to KRAS G12C inhibitors, leading to the&#xD;
        development of initial and acquired resistance to KRAS G12C inhibition. Based on this&#xD;
        hypothesis, a phase 1-2 clinical trial, known as the KRYSTAL-1 study, was conducted in&#xD;
        patients with metastatic colorectal cancer. The study demonstrated that the objective&#xD;
        response rate was 19% with adagrasib monotherapy and 46% with the combination of adagrasib&#xD;
        and cetuximab (an EGFR inhibitor), indicating that the addition of an EGFR inhibitor can&#xD;
        overcome resistance. Building on this hypothesis, a phase 3 trial is currently underway for&#xD;
        KRAS G12C inhibition plus EGFR blockade in metastatic colorectal cancer (ClinicalTrials.gov&#xD;
        identifiers: NCT04793958, NCT05198934).&#xD;
  &#xD;
        In this study, the aim is to investigate the efficacy of sotorasib (KRAS G12C inhibitor) plus&#xD;
        panitumumab (EGFR inhibitor) in patients with advanced solid tumors harboring KRAS G12C&#xD;
        mutations, who have failed standard treatments.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">July 3, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">September 4, 2023</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Objective response rate based on RECIST v1.1</measure>
      <time_frame>Imaging tumor assessment time point after Cycle 1 Day 1 (each cycle is 14 days).</time_frame>
      <description>Imaging tumor assessment time point after Cycle 1 Day 1 (each cycle is 14 days).</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">24</enrollment>
    <condition>Efficacy</condition>
    <arm_group>
      <arm_group_label>Oral sotorasib + IV Panitumumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Oral sotorasib at a dose of 960 mg once daily with Panitumumab is administered intravenously (IV) at a dose of 6 mg/kg every 14 days, infused over 60 minutes (≤ 1,000 mg) or 90 minutes (&gt; 1,000 mg).</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Oral sotorasib + IV Panitumumab</intervention_name>
      <description>Oral sotorasib at a dose of 960 mg once daily with Panitumumab is administered intravenously (IV) at a dose of 6 mg/kg every 14 days, infused over 60 minutes (≤ 1,000 mg) or 90 minutes (&gt; 1,000 mg).</description>
      <arm_group_label>Oral sotorasib + IV Panitumumab</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients who have consented to participate in the KOSMOS-II observational master&#xD;
               study.&#xD;
  &#xD;
            -  Age of 19 years or older.&#xD;
  &#xD;
            -  Histologically confirmed locally advanced or metastatic solid tumors (excluding&#xD;
               non-small cell lung cancer and colorectal cancer) with KRAS G12C mutation detected&#xD;
               through local next-generation sequencing analysis.&#xD;
  &#xD;
            -  Local advanced or metastatic disease with disease progression or unavailability of&#xD;
               standard treatment options for the first-line anti-cancer therapy.&#xD;
  &#xD;
            -  Measurable lesions according to RECIST v1.1 (lesions that have not experienced disease&#xD;
               progression after radiation therapy are excluded).&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.&#xD;
  &#xD;
            -  Adequate bone marrow and organ function as described below:&#xD;
  &#xD;
               ① Bone Marrow: - Absolute neutrophil count (ANC) ≥ 1,500/mm3 - Platelet count (PLT) ≥&#xD;
               100,000/mm3 - Hemoglobin (Hb) ≥ 9 g/dL&#xD;
  &#xD;
               ② Liver Function:&#xD;
  &#xD;
            -  Total bilirubin ≤ 1.5 X upper limit of normal (ULN). If liver metastasis is present,&#xD;
               total bilirubin up to ≤ 3 X ULN is allowed. For patients with Gilbert's syndrome,&#xD;
               total bilirubin up to ≤ 3 X ULN and direct bilirubin within the normal range is&#xD;
               allowed.&#xD;
  &#xD;
            -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 X ULN (or ≤ 5&#xD;
               X ULN if liver metastasis is present).&#xD;
  &#xD;
               ③ Renal Function: - Creatinine clearance ≥ 30 mL/min/1.73m2 (using the Cockcroft-Gault&#xD;
               formula).&#xD;
  &#xD;
            -  Estimated life expectancy of at least 3 months according to the investigator's&#xD;
               judgment.&#xD;
  &#xD;
            -  Ability to take oral medications.&#xD;
  &#xD;
            -  Understanding and compliance with the clinical trial protocol and ability to provide&#xD;
               informed consent by signing the informed consent form.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients who have not received previous sotorasib treatment or monoclonal antibodies&#xD;
               against epidermal growth factor receptor (EGFR) such as cetuximab or panitumumab.&#xD;
  &#xD;
            -  Absence of active brain metastasis or leptomeningeal metastasis (Patients with&#xD;
               previously treated brain metastasis or leptomeningeal metastasis with radiation&#xD;
               therapy and/or surgery [including radiosurgery] and are neurologically stable can be&#xD;
               eligible for enrollment).&#xD;
  &#xD;
            -  No significant cardiovascular events within the past 6 months, such as:&#xD;
  &#xD;
          .NYHA Class 3 or higher congestive heart failure. .Unstable angina or myocardial&#xD;
          infarction. .Uncontrolled or symptomatic atrial fibrillation. .QTc prolongation (&gt; 480&#xD;
          milliseconds).&#xD;
  &#xD;
            -  No history of stroke within the past 6 months (including transient ischemic attack).&#xD;
  &#xD;
            -  No diagnosis of another malignancy within 2 years prior to enrollment (excluding&#xD;
               superficial basal cell carcinoma or squamous cell carcinoma, cervical intraepithelial&#xD;
               neoplasia, prostate cancer under active surveillance, and well-differentiated thyroid&#xD;
               cancer that has undergone definitive surgery).&#xD;
  &#xD;
            -  Pregnant or breastfeeding women.&#xD;
  &#xD;
            -  Participants who do not agree to effective contraception* during the clinical trial.&#xD;
  &#xD;
            -  Sexually active female participants of childbearing potential and their partners must&#xD;
               agree to use medically acceptable contraception (e.g., male condoms, female condoms,&#xD;
               or the combined use of barrier methods and spermicidal gel) during the clinical trial&#xD;
               period and for up to 6 months after the last administration of the investigational&#xD;
               drug.&#xD;
  &#xD;
            -  Male participants who have not undergone vasectomy must agree to use barrier&#xD;
               contraception (condoms) and are prohibited from providing sperm donations until 6&#xD;
               months after the last administration of the investigational drug.&#xD;
  &#xD;
            -  Participants with active hepatitis B, hepatitis C, or human immunodeficiency virus&#xD;
               (HIV) infection, except under the following conditions:&#xD;
  &#xD;
            -  Participants who are positive for HBsAg (Hepatitis B surface antigen) can be enrolled&#xD;
               if ALT is within the normal range and HBV DNA is &lt;2,000 IU/ml while receiving&#xD;
               antiviral prophylaxis for hepatitis B reactivation.&#xD;
  &#xD;
            -  Participants who are negative for HBsAg but positive for Hepatitis B core antibody&#xD;
               (IgG anti-HBc) can be enrolled if HBV DNA is quantifiable but below the limit of&#xD;
               quantification.&#xD;
  &#xD;
            -  Participants who are positive for anti-HCV Ab can be enrolled if HCV RNA is&#xD;
               quantifiable but below the limit of quantification.&#xD;
  &#xD;
            -  Participants with planned major surgery during the clinical trial.&#xD;
  &#xD;
            -  Other clinically significant disorders deemed unsuitable for the clinical trial by the&#xD;
               investigator.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>19 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Korea University Anam Hospital</name>
        <address>
          <city>Seoul</city>
          <zip>02841</zip>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Korea, Republic of</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 3, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Korea University Anam Hospital</investigator_affiliation>
      <investigator_full_name>Lee, Soo Hyeon</investigator_full_name>
      <investigator_title>Associate professor</investigator_title>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Panitumumab</mesh_term>
      <mesh_term>Sotorasib</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05993455
  org study id: KRAUS
  nct id: NCT05993455
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Kirsten rat sarcoma (KRAS) mutation is one of the most common genetic mutations associated
        with tumor development in various human cancers, including pancreatic cancer, non-small cell
        lung cancer, and colorectal cancer. Previous studies have shown that KRAS mutations are
        present in approximately 70% of pancreatic cancer patients, 35% of colorectal cancer
        patients, 20% of non-small cell lung cancer patients, and 15% of cervical cancer patients.
        Patients with KRAS mutations generally have a shorter overall survival and increased
        resistance to treatment compared to wild-type tumors. KRAS mutations have been known for
        decades, but they have been considered "undruggable" as effective therapies targeting them
        were lacking.
  
        Preclinical studies focusing on colorectal and non-small cell lung cancer cell lines have
        suggested that colorectal cancer cell lines exhibit a stronger response to EGFR signaling and
        activation of multiple RTKs (Receptor Tyrosine Kinases) than non-small cell lung cancer cell
        lines. As a result, they show poorer responses to KRAS G12C inhibitors, leading to the
        development of initial and acquired resistance to KRAS G12C inhibition. Based on this
        hypothesis, a phase 1-2 clinical trial, known as the KRYSTAL-1 study, was conducted in
        patients with metastatic colorectal cancer. The study demonstrated that the objective
        response rate was 19% with adagrasib monotherapy and 46% with the combination of adagrasib
        and cetuximab (an EGFR inhibitor), indicating that the addition of an EGFR inhibitor can
        overcome resistance. Building on this hypothesis, a phase 3 trial is currently underway for
        KRAS G12C inhibition plus EGFR blockade in metastatic colorectal cancer (ClinicalTrials.gov
        identifiers: NCT04793958, NCT05198934).
  
        In this study, the aim is to investigate the efficacy of sotorasib (KRAS G12C inhibitor) plus
        panitumumab (EGFR inhibitor) in patients with advanced solid tumors harboring KRAS G12C
        mutations, who have failed standard treatments.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective response rate based on RECIST v1.1
  time frame: Imaging tumor assessment time point after Cycle 1 Day 1 (each cycle is 14 days).
  description: Imaging tumor assessment time point after Cycle 1 Day 1 (each cycle is 14 days).
  arm group label: Oral sotorasib + IV Panitumumab
  arm group type: Experimental
  description: Oral sotorasib at a dose of 960 mg once daily with Panitumumab is administered intravenously (IV) at a dose of 6 mg/kg every 14 days, infused over 60 minutes (≤ 1,000 mg) or 90 minutes (> 1,000 mg).
  intervention type: Drug
  intervention name: Oral sotorasib + IV Panitumumab
  description: Oral sotorasib at a dose of 960 mg once daily with Panitumumab is administered intravenously (IV) at a dose of 6 mg/kg every 14 days, infused over 60 minutes (≤ 1,000 mg) or 90 minutes (> 1,000 mg).
  arm group label: Oral sotorasib + IV Panitumumab
  criteria: 
  gender: All
  minimum age: 19 Years
  maximum age: N/A
  healthy volunteers: No
  facility: 
  country: Korea, Republic of
  responsible party type: Principal Investigator
  investigator affiliation: Korea University Anam Hospital
  investigator full name: Lee, Soo Hyeon
  investigator title: Associate professor
  mesh term: Panitumumab
  mesh term: Sotorasib