<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/NCT03263429</url>
  </required_header>
  <id_info>
    <org_study_id>VICC GI 1703</org_study_id>
    <secondary_id>NCI-2017-01461</secondary_id>
    <nct_id>NCT03263429</nct_id>
  </id_info>
  <brief_title>Novel PET/CT Imaging Biomarkers of CB-839 in Combination With Panitumumab and Irinotecan in Patients With Metastatic and Refractory RAS Wildtype Colorectal Cancer</brief_title>
  <official_title>Phase I/II Study to Evaluate the Safety, Efficacy, and Novel PET/CT Imaging Biomarkers of CB-839 in Combination With Panitumumab and Irinotecan in Patients With Metastatic and Refractory RAS Wildtype Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt-Ingram Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Calithera Biosciences, Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt-Ingram Cancer Center</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I/II trial studies the best dose and side effects of glutaminase inhibitor CB-839&#xD;
      and how well it works with panitumumab and irinotecan hydrochloride (phase I only) in&#xD;
      treating patients with RAS wildtype colorectal cancer that has spread to other places in the&#xD;
      body and does not respond to treatment. Glutaminase inhibitor CB-839 may stop the growth of&#xD;
      tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies,&#xD;
      such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Drugs&#xD;
      used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the&#xD;
      growth of tumor cells, either by killing the cells, by stopping them from dividing, or by&#xD;
      stopping them from spreading. Giving glutaminase inhibitor CB-839 with panitumumab and&#xD;
      irinotecan hydrochloride may work better in treating patients with colorectal cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives:&#xD;
&#xD;
      Primary Objective of Phase I:&#xD;
&#xD;
      • Determine the safety and tolerability of CB-839 in combination with panitumumab and&#xD;
      irinotecan.&#xD;
&#xD;
      Exploratory Objective of Phase I (Optional Imaging Sub-study):&#xD;
&#xD;
      • Correlate radiological features of pre- and post-treatment 11C-Glutamine PET/CT and&#xD;
      18F-FSPG PET/CT with clinical outcome.&#xD;
&#xD;
      Primary Objective of Phase II:&#xD;
&#xD;
      • Determine the efficacy of CB-839 in combination with panitumumab as measured by the&#xD;
      response rate (RR).&#xD;
&#xD;
      Secondary Objectives of Phase II:&#xD;
&#xD;
        -  Determine the disease control rate (DCR), progression-free survival (PFS), and overall&#xD;
           survival (OS).&#xD;
&#xD;
        -  Perform the following correlative studies (in the phase 2 component):&#xD;
&#xD;
        -  Correlate radiological features of pre- and post-treatment 18F-FSPG PET/CT with clinical&#xD;
           outcome and biological correlates (tissue gene signature, exosomes).&#xD;
&#xD;
        -  Collect blood samples during each radiotracer injection to assess pharmacokinetics.&#xD;
&#xD;
        -  Collect pre-treatment biopsy tissue and prospectively correlate clinical outcome with a&#xD;
           glutamine metabolism gene signature.&#xD;
&#xD;
        -  Quantify exosomal content in the plasma.&#xD;
&#xD;
      Exploratory Objective of Phase II:&#xD;
&#xD;
      • Development of patient-derived organoids from pre-treatment tissue biopsy&#xD;
&#xD;
      OUTLINE: Phase I is a dose-escalation study of glutaminase inhibitor CB-839 in combination&#xD;
      with standard doses of panitumumab and irinotecan hydrochloride. Phase II will study efficacy&#xD;
      of glutaminase inhibitor CB-839 in combination with standard doses of panitumumab.&#xD;
&#xD;
      Patients receive glutaminase inhibitor CB-839 orally (PO) twice daily (BID) on days 1-28,&#xD;
      panitumumab intravenously (IV) over 60-90 minutes on days 1 and 15, and irinotecan&#xD;
      hydrochloride IV over 90 minutes on day 1 and 15 (Phase I only). Courses repeat every 28 days&#xD;
      in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed at 28 days and then every 3 months&#xD;
      for up to 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 23, 2017</start_date>
  <completion_date type="Anticipated">December 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2023</primary_completion_date>
  <phase>Phase 1/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>Maximum tolerated dose (Phase I) B-839 in combination with panitumumab and irinotecan hydrochloride</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>The maximum tolerated dose will be determined</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response rate (Phase II)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Will use Simon's optimal 2-stage design to monitor efficacy in this trial.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended phase 2 dose of CB-839 in combination with panitumumab and irinotecan hydrochloride (Phase I)</measure>
    <time_frame>Up to 12 months.</time_frame>
    <description>The recommended phase 2 dose will be determined.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>The disease control rate will be evaluated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Standardized Uptake Value (SUVmax) of fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) uptake (Phase II)</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>evaluate the relationship between 18F-FSPG uptake at baseline and change in tumor size at the time of objective response assessment using a standard linear regression analysis. The slope will describe the shape of the relationship between SUVmax and change in tumor size, while the coefficient of determination (R2) describes the strength of the relationship between the two measures. A similar linear regression analysis will be conducted to quantify the relationship between the change in SUVmax as measured from baseline to after one cycle of therapy and change in tumor size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma exosomal content (phase II)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Plasma exosomal content will be assessed at pre-treatment, after one cycle of treatment, and at disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (phase II)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>will use Cox proportional hazards model to estimate the association between PET SUVmax and OS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>will use Cox proportional hazards model to estimate the association between PET SUVmax and OS.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Colorectal Cancer</condition>
  <condition>Metastatic Colorectal Cancer</condition>
  <condition>RAS Wild Type Colorectal Cancer</condition>
  <condition>Refractory Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Panitumumab/Irinotecan/CB-839</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive glutaminase inhibitor CB-839 PO BID on days 1-28, panitumumab IV over 60-90 minutes on days 1 and 15, and irinotecan hydrochloride IV over 90 minutes on day 1 and 15 (Phase I only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glutaminase Inhibitor CB-839</intervention_name>
    <description>Given by mouth</description>
    <arm_group_label>Panitumumab/Irinotecan/CB-839</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Panitumumab</intervention_name>
    <description>Given by vein</description>
    <arm_group_label>Panitumumab/Irinotecan/CB-839</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan Hydrochloride (phase I only)</intervention_name>
    <description>Given by vein</description>
    <arm_group_label>Panitumumab/Irinotecan/CB-839</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Panitumumab/Irinotecan/CB-839</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Panitumumab/Irinotecan/CB-839</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Imaging with 11C-Glutamine PET/CT scans and 18F-FSPG PET/CT scans</intervention_name>
    <description>During phase II at baseline and day 28 of cycle 1</description>
    <arm_group_label>Panitumumab/Irinotecan/CB-839</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed and dated written informed consent&#xD;
&#xD;
          -  Histologically or cytologically-confirmed diagnosis of metastatic KRAS wildtype&#xD;
             colorectal cancer (CRC)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  In dose escalation, patients must have had at least one prior line of chemotherapy for&#xD;
             advanced disease or progressed within 6 months of adjuvant therapy (prior chemotherapy&#xD;
             and/or anti-EGFR therapy is permitted)&#xD;
&#xD;
          -  In dose expansion, patients must have received prior anti-EGFR therapy and achieved at&#xD;
             least stable disease on at least one scan as their best response&#xD;
&#xD;
          -  In dose expansion, patients must be willing to undergo a pre-treatment biopsy, and&#xD;
             four research PET imaging techniques (11C-Glutamine and 18F-FSPG), two pre-treatment&#xD;
             and two after one cycle of treatment&#xD;
&#xD;
          -  In dose expansion, at least one measurable lesion as defined by Response Evaluation&#xD;
             Criteria in Solid Tumors (RECIST) 1.1 which can be followed by CT or magnetic&#xD;
             resonance imaging (MRI)&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500/uL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/uL&#xD;
&#xD;
          -  Serum albumin &gt;= 3.0 g/dL&#xD;
&#xD;
          -  Serum creatinine =&lt; 2 mg/dL, or calculated creatinine clearance &gt; 50 mL/min (per the&#xD;
             Cockcroft-Gault formula)&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 times upper limit of normal (ULN)&#xD;
&#xD;
          -  Aspartate transaminase (AST) and alanine aminotransferase (ALT) =&lt; 5.0 x ULN&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP) must have a negative serum pregnancy test&#xD;
             within 14 days prior to receiving first dose of protocol-indicated treatment; and&#xD;
             additionally agree to use at least 2 methods of acceptable contraception or abstain&#xD;
             from heterosexual intercourse from the time of signing consent, and until 2 months&#xD;
             after patient's last dose of protocol-indicated treatment; WOCBP of childbearing&#xD;
             potential are defined as those not surgically sterile or not post-menopausal (i.e. if&#xD;
             a female patient has not had a bilateral tubal ligation, a bilateral oophorectomy, or&#xD;
             a complete hysterectomy; or has not been amenorrheic for 12 months in the absence of&#xD;
             an alternative medical cause, then patient will be considered a female of childbearing&#xD;
             potential); postmenopausal status in females under 55 years of age should be confirmed&#xD;
             with a serum follicle-stimulating hormone (FSH) level within laboratory reference&#xD;
             range for postmenopausal women&#xD;
&#xD;
          -  Men able to father children who are sexually active with WOCBP must agree to use at&#xD;
             least 2 methods of acceptable contraception from the time of signing consent and until&#xD;
             2 months after patient's last dose of protocol-indicated treatment; men able to father&#xD;
             children are defined as those who are not surgically sterile (i.e. patient has not had&#xD;
             a vasectomy)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Within 28 days before first dose of protocol-indicated treatment:&#xD;
&#xD;
               -  Anti-cancer treatment including chemotherapy, radiation, hormonal therapy,&#xD;
                  targeted therapy, immunotherapy, or biological therapy&#xD;
&#xD;
               -  Major surgery requiring general anesthesia; (Note: within this time frame,&#xD;
                  placement of a central line or portacath is acceptable and does not exclude)&#xD;
&#xD;
               -  Receipt of an investigational agent&#xD;
&#xD;
          -  Within 14 days before first dose of protocol-indicated treatment:&#xD;
&#xD;
             * Active uncontrolled infection; patients with infection under active treatment and&#xD;
             controlled with antibiotics initiated at least 14 days prior to initiation of&#xD;
             protocol-indicated treatment are not excluded (e.g. urinary tract infection controlled&#xD;
             with antibiotics)&#xD;
&#xD;
          -  Dose escalation only: known grade 4 toxicity probably or definitely attributed to past&#xD;
             irinotecan treatment&#xD;
&#xD;
          -  Active inflammatory bowel disease, other bowel disease causing chronic diarrhea&#xD;
             (defined as &gt; 4 loose stools per day), or bowel obstruction&#xD;
&#xD;
          -  History of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial&#xD;
             pneumonitis or pulmonary fibrosis on baseline chest CT scan&#xD;
&#xD;
          -  Unable to receive oral medication&#xD;
&#xD;
          -  Central nervous system (CNS) metastasis, unless asymptomatic or previously treated and&#xD;
             stable; and no evidence of CNS progression for at least 30 days prior to initiating&#xD;
             protocol-indicated treatment; anticonvulsant and/or corticosteroid therapy will be&#xD;
             allowed if patient is on a stable or decreasing dose of such treatment for at least 30&#xD;
             days prior to initiating protocol-indicated treatment&#xD;
&#xD;
          -  Patients with known Gilbert's disease&#xD;
&#xD;
          -  Patient is pregnant or breastfeeding&#xD;
&#xD;
          -  Current or previous malignant disease (other than colorectal cancer) within the last 5&#xD;
             years; with the exception of the following if considered curatively treated:&#xD;
             non-melanoma skin cancer(s), carcinoma in situ of the cervix, and ductal carcinoma in&#xD;
             situ; subjects with another active malignancy requiring concurrent anti-cancer&#xD;
             intervention are excluded; (Note the following does not exclude: effectively treated&#xD;
             malignancy that has been in remission for more than 5 years and is considered to be&#xD;
             cured AND no additional anti-cancer therapy is ongoing and required during the study&#xD;
             period)&#xD;
&#xD;
          -  Known positive test for human immunodeficiency virus (HIV), acquired immunodeficiency&#xD;
             syndrome (AIDS), hepatitis A, hepatitis B, hepatitis C, or cytomegalovirus (CMV)&#xD;
&#xD;
          -  Known psychiatric condition, social circumstance, or other medical condition&#xD;
             reasonably judged by the patient's study physician to unacceptably increase the risk&#xD;
             of study participation; or to prohibit the understanding or rendering of informed&#xD;
             consent or anticipated compliance with scheduled visits, treatment schedule,&#xD;
             laboratory tests and other study requirements.&#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>Jordan Berlin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt-Ingram Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt-Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>March 2, 2023</last_update_submitted>
  <last_update_submitted_qc>March 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt-Ingram Cancer Center</investigator_affiliation>
    <investigator_full_name>Jordan Berlin, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irinotecan</mesh_term>
    <mesh_term>Panitumumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <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>January 18, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT03263429/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03263429
org study id: VICC GI 1703
secondary id: NCI-2017-01461
nct id: NCT03263429
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I/II trial studies the best dose and side effects of glutaminase inhibitor CB-839
      and how well it works with panitumumab and irinotecan hydrochloride (phase I only) in
      treating patients with RAS wildtype colorectal cancer that has spread to other places in the
      body and does not respond to treatment. Glutaminase inhibitor CB-839 may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies,
      such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Drugs
      used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the
      growth of tumor cells, either by killing the cells, by stopping them from dividing, or by
      stopping them from spreading. Giving glutaminase inhibitor CB-839 with panitumumab and
      irinotecan hydrochloride may work better in treating patients with colorectal cancer.
Objectives:

      Primary Objective of Phase I:

      • Determine the safety and tolerability of CB-839 in combination with panitumumab and
      irinotecan.

      Exploratory Objective of Phase I (Optional Imaging Sub-study):

      • Correlate radiological features of pre- and post-treatment 11C-Glutamine PET/CT and
      18F-FSPG PET/CT with clinical outcome.

      Primary Objective of Phase II:

      • Determine the efficacy of CB-839 in combination with panitumumab as measured by the
      response rate (RR).

      Secondary Objectives of Phase II:

        -  Determine the disease control rate (DCR), progression-free survival (PFS), and overall
           survival (OS).

        -  Perform the following correlative studies (in the phase 2 component):

        -  Correlate radiological features of pre- and post-treatment 18F-FSPG PET/CT with clinical
           outcome and biological correlates (tissue gene signature, exosomes).

        -  Collect blood samples during each radiotracer injection to assess pharmacokinetics.

        -  Collect pre-treatment biopsy tissue and prospectively correlate clinical outcome with a
           glutamine metabolism gene signature.

        -  Quantify exosomal content in the plasma.

      Exploratory Objective of Phase II:

      • Development of patient-derived organoids from pre-treatment tissue biopsy

      OUTLINE: Phase I is a dose-escalation study of glutaminase inhibitor CB-839 in combination
      with standard doses of panitumumab and irinotecan hydrochloride. Phase II will study efficacy
      of glutaminase inhibitor CB-839 in combination with standard doses of panitumumab.

      Patients receive glutaminase inhibitor CB-839 orally (PO) twice daily (BID) on days 1-28,
      panitumumab intravenously (IV) over 60-90 minutes on days 1 and 15, and irinotecan
      hydrochloride IV over 90 minutes on day 1 and 15 (Phase I only). Courses repeat every 28 days
      in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed at 28 days and then every 3 months
      for up to 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (Phase I) B-839 in combination with panitumumab and irinotecan hydrochloride
time frame: Up to 12 months
description: The maximum tolerated dose will be determined
measure: Response rate (Phase II)
time frame: Up to 12 months
description: Will use Simon's optimal 2-stage design to monitor efficacy in this trial.
measure: Recommended phase 2 dose of CB-839 in combination with panitumumab and irinotecan hydrochloride (Phase I)
time frame: Up to 12 months.
description: The recommended phase 2 dose will be determined.
measure: Disease control rate
time frame: Up to 12 months
description: The disease control rate will be evaluated.
measure: Maximum Standardized Uptake Value (SUVmax) of fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) uptake (Phase II)
time frame: Up to 8 weeks
description: evaluate the relationship between 18F-FSPG uptake at baseline and change in tumor size at the time of objective response assessment using a standard linear regression analysis. The slope will describe the shape of the relationship between SUVmax and change in tumor size, while the coefficient of determination (R2) describes the strength of the relationship between the two measures. A similar linear regression analysis will be conducted to quantify the relationship between the change in SUVmax as measured from baseline to after one cycle of therapy and change in tumor size.
measure: Plasma exosomal content (phase II)
time frame: Up to 12 months
description: Plasma exosomal content will be assessed at pre-treatment, after one cycle of treatment, and at disease progression.
measure: Progression free survival (phase II)
time frame: Up to 12 months
description: will use Cox proportional hazards model to estimate the association between PET SUVmax and OS.
measure: Overall Survival
time frame: Up to 12 months
description: will use Cox proportional hazards model to estimate the association between PET SUVmax and OS.
arm group label: Panitumumab/Irinotecan/CB-839
arm group type: Experimental
description: Patients receive glutaminase inhibitor CB-839 PO BID on days 1-28, panitumumab IV over 60-90 minutes on days 1 and 15, and irinotecan hydrochloride IV over 90 minutes on day 1 and 15 (Phase I only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Glutaminase Inhibitor CB-839
description: Given by mouth
arm group label: Panitumumab/Irinotecan/CB-839
intervention type: Biological
intervention name: Panitumumab
description: Given by vein
arm group label: Panitumumab/Irinotecan/CB-839
intervention type: Drug
intervention name: Irinotecan Hydrochloride (phase I only)
description: Given by vein
arm group label: Panitumumab/Irinotecan/CB-839
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Panitumumab/Irinotecan/CB-839
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Panitumumab/Irinotecan/CB-839
intervention type: Device
intervention name: Imaging with 11C-Glutamine PET/CT scans and 18F-FSPG PET/CT scans
description: During phase II at baseline and day 28 of cycle 1
arm group label: Panitumumab/Irinotecan/CB-839
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jordan Berlin, MD
role: Principal Investigator
affiliation: Vanderbilt-Ingram Cancer Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt-Ingram Cancer Center
investigator full name: Jordan Berlin, MD
investigator title: Principal Investigator
mesh term: Colorectal Neoplasms
mesh term: Irinotecan
mesh term: Panitumumab
provided document: 