<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/NCT02215928</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-29525</org_study_id>
    <secondary_id>NCI-2014-01662</secondary_id>
    <secondary_id>VAR0114</secondary_id>
    <nct_id>NCT02215928</nct_id>
  </id_info>
  <brief_title>Genomic Profiling in Recommending Treatment for Patients With Metastatic Solid Tumors</brief_title>
  <official_title>Tumor Genomic Profiling: A Personalized Medicine Approach</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research trial studies using genomic profiling to recommend anticancer treatment to&#xD;
      patients with cancer that has spread beyond the original site of the tumor (metastatic&#xD;
      cancer). Genomic profiling studies the deoxyribonucleic acid (DNA) of a tumor to detect&#xD;
      genetic changes or abnormalities. This information can then be used to recommend treatments&#xD;
      that may be more likely to result in a beneficial response. It is not yet known whether&#xD;
      genomic profiling will detect abnormalities that can be used to make treatment&#xD;
      recommendations and whether treatment based on genomic profiling is more effective than&#xD;
      standard treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Assess the feasibility of integrating tumor genomic profiling in the adult oncology clinic&#xD;
      at the Stanford Cancer Institute.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Determine the percentage of tumors that harbor &quot;actionable&quot; genomic changes. II. Explore&#xD;
      effects of individual molecular profiling including the percent of time that profiling&#xD;
      changes the treatment.&#xD;
&#xD;
      III. Determine the number of cases in which a genomically identified targeted therapy is&#xD;
      available.&#xD;
&#xD;
      IV. Determine the clinical benefit of genomic based therapy, as defined by: response rate&#xD;
      (according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 response criteria);&#xD;
      the percent of patients with non-progression at 4 months, and overall survival, in patients&#xD;
      whose therapy is selected based on profiling.&#xD;
&#xD;
      V. Determine if circulating free tumor DNA (ctDNA) in the blood stream (liquid biopsy) yields&#xD;
      similar genomic results as the metastatic tumor analysis.&#xD;
&#xD;
      VI. Determine if ctDNA analysis during treatment correlates with RECIST 1.1 criteria in&#xD;
      predicting response.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Tissue samples are collected at baseline and blood for liquid biopsy is collected at baseline&#xD;
      and every 6-8 weeks during active treatment. Tissue samples are analyzed via sequencing for&#xD;
      tumor genomic profiling.&#xD;
&#xD;
      After completion of active treatment, participants are followed up at 4, 8, 12, 18, and 24&#xD;
      months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 28, 2014</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility, measured as the proportion of patients with at least one actionable alteration</measure>
    <time_frame>Baseline</time_frame>
    <description>An actionable alteration is defined as availability of targeted therapy, scored as: A) an FDA-approved drug, B) an FDA-approved drug in another tumor type, or C) a drug that is not yet approved but has a clinical trial open. The percentage of patients in the &quot;profile&quot; arm with successful profiling will be calculated and further characterized by availability category.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Drugs (if any) that target alterations found in a patient's tumor material at baseline, as identified by the Molecular Tumor Board</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drugs (if any) that target alterations found in a patient's peripheral blood at baseline, as identified by the Molecular Tumor Board</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Availability of targeted therapy from tumor material scored as category A, B, or C above or D) No target therapy available, or no genetic alterations found</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Number of days from enrollment to death, assessed up to 24 months</time_frame>
    <description>Overall survival of patients in each cohort will be characterized using Kaplan-Meier plots and the two cohorts will be compared using a Cox model to control for age and sex.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical response rate, assessed according to RECIST 1.1 criteria</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Response will be compared using logistic regression, adjusting for the same risk factors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 30 days after last dose of active treatment</time_frame>
    <description>Categorized by grade and MedDRA preferred term.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor-based genomics</measure>
    <time_frame>Baseline</time_frame>
    <description>Comparison of tumor-based genomics with peripheral-blood genomics will be carried out by comparing the list of genetic aberrations found in the two different samples (tumor vs ctDNA) and possible target drugs identified from each source. Agreement on success of profiling will be assessed using a kappa statistic.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral-blood genomics</measure>
    <time_frame>Baseline</time_frame>
    <description>Comparison of tumor-based genomics with peripheral-blood genomics will be carried out by comparing the list of genetic aberrations found in the two different samples (tumor vs ctDNA) and possible target drugs identified from each source. Agreement on success of profiling will be assessed using a kappa statistic.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Unspecified Adult Solid Tumor, Protocol Specific</condition>
  <arm_group>
    <arm_group_label>Ancillary-correlative (tumor genomic profiling)</arm_group_label>
    <description>Tissue samples are collected at baseline and blood for liquid biopsy is collected at baseline and every 6-8 weeks during active treatment. Tissue samples are analyzed via sequencing for tumor genomic profiling.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>mutation analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Ancillary-correlative (tumor genomic profiling)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>cytology specimen collection procedure</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Ancillary-correlative (tumor genomic profiling)</arm_group_label>
    <other_name>cytologic sampling</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Ancillary-correlative (tumor genomic profiling)</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      liquid biopsy&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        adult oncology clinic at the Stanford Cancer Institute&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Understand and provide written informed consent and Health Insurance Portability and&#xD;
             Accountability Act (HIPAA) authorization prior to initiation of any study-specific&#xD;
             procedures&#xD;
&#xD;
          -  Have a diagnosis of metastatic, incurable cancer and have progressed on at least one&#xD;
             line of systemic therapy OR a cancer with no standard 1st-line systemic therapy shown&#xD;
             to prolong survival (or where a clinical trial recommended as the 1st-line option)&#xD;
&#xD;
          -  Measurable disease (RECIST 1.1)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1&#xD;
&#xD;
          -  In the opinion of the investigator, be medically suitable for and willing to undergo a&#xD;
             biopsy or surgical procedure to obtain tissue as a part of routine care for their&#xD;
             malignancy OR have adequate archival tissue from a previous biopsy available for&#xD;
             profiling&#xD;
&#xD;
          -  Female patients of childbearing potential must have a negative pregnancy test and&#xD;
             agree to use at least one form of contraception during the study and for at least one&#xD;
             month after treatment discontinuation; for the purposes of this study, child-bearing&#xD;
             potential is defined as: all female patients that were not in post-menopause for at&#xD;
             least one year or are surgically sterile&#xD;
&#xD;
          -  Male patients must use a form of barrier contraception approved by the&#xD;
             investigator/treating physician during the study and for at least one month after&#xD;
             treatment discontinuation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have lesions that are not accessible to biopsy or not planned for biopsy as part of&#xD;
             routine care OR if archival tissue will be used for profiling, an insufficient amount&#xD;
             is available&#xD;
&#xD;
          -  Have diagnosis of a hematologic malignancy&#xD;
&#xD;
          -  Have symptomatic central nervous system (CNS) metastasis; patients with a history of&#xD;
             CNS metastases who have been treated with whole brain irradiation must be stable&#xD;
             without symptoms for 4 weeks after completion of treatment, with image documentation&#xD;
             required, and must be either off steroids or on a stable dose of steroids for &gt;= 2&#xD;
             weeks prior to enrollment&#xD;
&#xD;
          -  Have uncontrolled concurrent illness including, but not limited to, ongoing or active&#xD;
             serious infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             unstable cardiac arrhythmias, psychiatric illness, or situations that would limit&#xD;
             compliance with the study requirements or the ability to willingly give written&#xD;
             informed consent&#xD;
&#xD;
          -  Have known human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C&#xD;
             virus (HCV) infection&#xD;
&#xD;
          -  Are pregnant or breast-feeding patients or any patient with childbearing potential not&#xD;
             using adequate contraception&#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>James Ford</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University Hospitals and Clinics</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Meredith Mills</last_name>
    <phone>650-724-5223</phone>
    <email>bluett@stanford.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Stanford University Hospitals and Clinics</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Meredith Mills</last_name>
      <phone>650-724-5223</phone>
      <email>bluett@stanford.edu</email>
    </contact>
    <investigator>
      <last_name>James M. Ford</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>September 9, 2022</last_update_submitted>
  <last_update_submitted_qc>September 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT02215928
org study id: IRB-29525
secondary id: NCI-2014-01662
secondary id: VAR0114
nct id: NCT02215928
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This research trial studies using genomic profiling to recommend anticancer treatment to
      patients with cancer that has spread beyond the original site of the tumor (metastatic
      cancer). Genomic profiling studies the deoxyribonucleic acid (DNA) of a tumor to detect
      genetic changes or abnormalities. This information can then be used to recommend treatments
      that may be more likely to result in a beneficial response. It is not yet known whether
      genomic profiling will detect abnormalities that can be used to make treatment
      recommendations and whether treatment based on genomic profiling is more effective than
      standard treatment.
PRIMARY OBJECTIVES:

      I. Assess the feasibility of integrating tumor genomic profiling in the adult oncology clinic
      at the Stanford Cancer Institute.

      SECONDARY OBJECTIVES:

      I. Determine the percentage of tumors that harbor "actionable" genomic changes. II. Explore
      effects of individual molecular profiling including the percent of time that profiling
      changes the treatment.

      III. Determine the number of cases in which a genomically identified targeted therapy is
      available.

      IV. Determine the clinical benefit of genomic based therapy, as defined by: response rate
      (according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 response criteria);
      the percent of patients with non-progression at 4 months, and overall survival, in patients
      whose therapy is selected based on profiling.

      V. Determine if circulating free tumor DNA (ctDNA) in the blood stream (liquid biopsy) yields
      similar genomic results as the metastatic tumor analysis.

      VI. Determine if ctDNA analysis during treatment correlates with RECIST 1.1 criteria in
      predicting response.

      OUTLINE:

      Tissue samples are collected at baseline and blood for liquid biopsy is collected at baseline
      and every 6-8 weeks during active treatment. Tissue samples are analyzed via sequencing for
      tumor genomic profiling.

      After completion of active treatment, participants are followed up at 4, 8, 12, 18, and 24
      months.
observational model: Other
time perspective: Other
measure: Feasibility, measured as the proportion of patients with at least one actionable alteration
time frame: Baseline
description: An actionable alteration is defined as availability of targeted therapy, scored as: A) an FDA-approved drug, B) an FDA-approved drug in another tumor type, or C) a drug that is not yet approved but has a clinical trial open. The percentage of patients in the "profile" arm with successful profiling will be calculated and further characterized by availability category.
measure: Drugs (if any) that target alterations found in a patient's tumor material at baseline, as identified by the Molecular Tumor Board
time frame: Baseline
measure: Drugs (if any) that target alterations found in a patient's peripheral blood at baseline, as identified by the Molecular Tumor Board
time frame: Baseline
measure: Availability of targeted therapy from tumor material scored as category A, B, or C above or D) No target therapy available, or no genetic alterations found
time frame: Baseline
measure: Overall survival
time frame: Number of days from enrollment to death, assessed up to 24 months
description: Overall survival of patients in each cohort will be characterized using Kaplan-Meier plots and the two cohorts will be compared using a Cox model to control for age and sex.
measure: Clinical response rate, assessed according to RECIST 1.1 criteria
time frame: Up to 24 months
description: Response will be compared using logistic regression, adjusting for the same risk factors.
measure: Incidence of adverse events
time frame: Up to 30 days after last dose of active treatment
description: Categorized by grade and MedDRA preferred term.
measure: Tumor-based genomics
time frame: Baseline
description: Comparison of tumor-based genomics with peripheral-blood genomics will be carried out by comparing the list of genetic aberrations found in the two different samples (tumor vs ctDNA) and possible target drugs identified from each source. Agreement on success of profiling will be assessed using a kappa statistic.
measure: Peripheral-blood genomics
time frame: Baseline
description: Comparison of tumor-based genomics with peripheral-blood genomics will be carried out by comparing the list of genetic aberrations found in the two different samples (tumor vs ctDNA) and possible target drugs identified from each source. Agreement on success of profiling will be assessed using a kappa statistic.
arm group label: Ancillary-correlative (tumor genomic profiling)
description: Tissue samples are collected at baseline and blood for liquid biopsy is collected at baseline and every 6-8 weeks during active treatment. Tissue samples are analyzed via sequencing for tumor genomic profiling.
intervention type: Genetic
intervention name: mutation analysis
description: Correlative studies
arm group label: Ancillary-correlative (tumor genomic profiling)
intervention type: Other
intervention name: cytology specimen collection procedure
description: Correlative studies
arm group label: Ancillary-correlative (tumor genomic profiling)
other name: cytologic sampling
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative studies
arm group label: Ancillary-correlative (tumor genomic profiling)
liquid biopsy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James Ford
role: Principal Investigator
affiliation: Stanford University Hospitals and Clinics
last name: Meredith Mills
phone: 650-724-5223
email: bluett@stanford.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor