<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/NCT03795610</url>
  </required_header>
  <id_info>
    <org_study_id>172058</org_study_id>
    <nct_id>NCT03795610</nct_id>
  </id_info>
  <brief_title>Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma</brief_title>
  <official_title>Phase 2 Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ezra Cohen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The V Foundation for Cancer Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Diego</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>
      The purpose of this study is to investigate how effective the study drug IPI-549 is against&#xD;
      types of cancers. IPI-549 is considered experimental because it is not approved by the US&#xD;
      Food and Drug Administration (FDA) for the treatment of cancer.&#xD;
&#xD;
      Patients will be treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue&#xD;
      for research purposes through core biopsies will be obtained prior to initiation of IPI-549&#xD;
      and at surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 2 window of opportunity trial in patients with locally advanced head and neck&#xD;
      cancer. A key objective is to provide the first proof that macrophage phenotype switching can&#xD;
      be accomplished in humans and lay the groundwork for future trials of this novel approach to&#xD;
      immune therapy. Patients who are candidates for surgical resection will be enrolled and&#xD;
      treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue for research&#xD;
      purposes through core biopsies will be obtained prior to initiation of IPI-549 and at&#xD;
      surgery.&#xD;
&#xD;
      The study team hypothesizes that mRNA signatures of immune response will be increased in&#xD;
      IPI-549-treated patients. For the efficacy endpoints, RECISTv1.1 will be used.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 6, 2020</start_date>
  <completion_date type="Anticipated">June 2023</completion_date>
  <primary_completion_date type="Anticipated">June 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <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>PI3K-y changes</measure>
    <time_frame>2 years</time_frame>
    <description>To detect IPI-549-induced changes in PI3Kγ-regulated signatures of immune suppression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes of Myeloid composition</measure>
    <time_frame>2 years</time_frame>
    <description>Compare pre- vs. post-treatment tumor tissue</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in T cell composition</measure>
    <time_frame>2 years</time_frame>
    <description>T cell receptor (TCR) sequencing at baseline, surgery, end of treatment or at time of disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v5.0</measure>
    <time_frame>2 years</time_frame>
    <description>To determine safety and tolerability of IPI-549 and change in tumor size in patients with locally advanced HNSCC</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Head and Neck Cancer</condition>
  <condition>Head and Neck Carcinoma</condition>
  <condition>Head and Neck Cancer Stage IV</condition>
  <condition>Head and Neck Cancer Stage III</condition>
  <condition>HPV-Related Carcinoma</condition>
  <condition>HPV-Related Malignancy</condition>
  <condition>HPV-Related Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm A: IPI-549 40 mg PO qdaily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients enrolled in Arm A will receive IPI-549 40 mg by mouth daily for at least 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IPI-549</intervention_name>
    <description>40mg by mouth (PO) every day (QD) for at least 14 days</description>
    <arm_group_label>Arm A: IPI-549 40 mg PO qdaily</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have locally advanced that is amenable to surgical resection&#xD;
&#xD;
          -  Must be able to swallow tablets&#xD;
&#xD;
          -  Must be able to undergo a core tumor biopsy.&#xD;
&#xD;
          -  Must have adequate organ function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of cutaneous squamous cell carcinoma (SCC) or Epstein-Barr virus (EBV)&#xD;
             related nasopharynx cancer.&#xD;
&#xD;
          -  Planned major surgery within 4 weeks prior to initiation of study drug&#xD;
&#xD;
          -  Patients treated with chemotherapy, biologic therapy, or other investigational agent&#xD;
             within &lt; 28 days of starting study drug&#xD;
&#xD;
          -  History of infection with human immunodeficiency virus (HIV), hepatitis B, or&#xD;
             hepatitis C virus (HCV)&#xD;
&#xD;
          -  On going treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic&#xD;
             steroids&#xD;
&#xD;
          -  Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g.&#xD;
             gastric bypass surgery, gastrectomy)&#xD;
&#xD;
          -  Female subjects who are pregnant or breastfeeding&#xD;
&#xD;
          -  Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of&#xD;
             the cervix, or prostate intraepithelial neoplasia&#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>Ezra Cohen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Diego</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Debanjali Ghosh, MA</last_name>
    <phone>858-246-0357</phone>
    <email>d1ghosh@health.ucsd.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Elaine Eng</last_name>
    <email>e1eng@ucsd.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UC San Diego Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Kaneda MM, Cappello P, Nguyen AV, Ralainirina N, Hardamon CR, Foubert P, Schmid MC, Sun P, Mose E, Bouvet M, Lowy AM, Valasek MA, Sasik R, Novelli F, Hirsch E, Varner JA. Macrophage PI3Kgamma Drives Pancreatic Ductal Adenocarcinoma Progression. Cancer Discov. 2016 Aug;6(8):870-85. doi: 10.1158/2159-8290.CD-15-1346. Epub 2016 May 13.</citation>
    <PMID>27179037</PMID>
  </reference>
  <reference>
    <citation>Kaneda MM, Messer KS, Ralainirina N, Li H, Leem CJ, Gorjestani S, Woo G, Nguyen AV, Figueiredo CC, Foubert P, Schmid MC, Pink M, Winkler DG, Rausch M, Palombella VJ, Kutok J, McGovern K, Frazer KA, Wu X, Karin M, Sasik R, Cohen EE, Varner JA. PI3Kgamma is a molecular switch that controls immune suppression. Nature. 2016 Nov 17;539(7629):437-442. doi: 10.1038/nature19834. Epub 2016 Sep 19. Erratum In: Nature. 2017 Feb 2;542(7639):124.</citation>
    <PMID>27642729</PMID>
  </reference>
  <reference>
    <citation>De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell. 2013 Mar 18;23(3):277-86. doi: 10.1016/j.ccr.2013.02.013.</citation>
    <PMID>23518347</PMID>
  </reference>
  <reference>
    <citation>Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012 Mar 22;12(4):253-68. doi: 10.1038/nri3175.</citation>
    <PMID>22437938</PMID>
  </reference>
  <reference>
    <citation>Schmid MC, Avraamides CJ, Dippold HC, Franco I, Foubert P, Ellies LG, Acevedo LM, Manglicmot JR, Song X, Wrasidlo W, Blair SL, Ginsberg MH, Cheresh DA, Hirsch E, Field SJ, Varner JA. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kgamma, a single convergent point promoting tumor inflammation and progression. Cancer Cell. 2011 Jun 14;19(6):715-27. doi: 10.1016/j.ccr.2011.04.016.</citation>
    <PMID>21665146</PMID>
  </reference>
  <reference>
    <citation>Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.</citation>
    <PMID>19097774</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <last_update_submitted>March 8, 2023</last_update_submitted>
  <last_update_submitted_qc>March 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Ezra Cohen</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>HPV positive</keyword>
  <keyword>HPV negative</keyword>
  <keyword>HPV-</keyword>
  <keyword>HPV+</keyword>
  <keyword>PI3K-γ</keyword>
  <keyword>microenvironment</keyword>
  <keyword>immunotherapy</keyword>
  <keyword>tumor</keyword>
  <keyword>resection</keyword>
  <keyword>PI3K</keyword>
  <keyword>cancer</keyword>
  <keyword>carcinoma</keyword>
  <keyword>malignancy</keyword>
  <keyword>head</keyword>
  <keyword>neck</keyword>
  <keyword>throat</keyword>
  <keyword>esophageal</keyword>
  <keyword>nasopharyngeal</keyword>
  <keyword>nasopharynx</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <!-- 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/NCT03795610
org study id: 172058
nct id: NCT03795610
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to investigate how effective the study drug IPI-549 is against
      types of cancers. IPI-549 is considered experimental because it is not approved by the US
      Food and Drug Administration (FDA) for the treatment of cancer.

      Patients will be treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue
      for research purposes through core biopsies will be obtained prior to initiation of IPI-549
      and at surgery.
This is a phase 2 window of opportunity trial in patients with locally advanced head and neck
      cancer. A key objective is to provide the first proof that macrophage phenotype switching can
      be accomplished in humans and lay the groundwork for future trials of this novel approach to
      immune therapy. Patients who are candidates for surgical resection will be enrolled and
      treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue for research
      purposes through core biopsies will be obtained prior to initiation of IPI-549 and at
      surgery.

      The study team hypothesizes that mRNA signatures of immune response will be increased in
      IPI-549-treated patients. For the efficacy endpoints, RECISTv1.1 will be used.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PI3K-y changes
time frame: 2 years
description: To detect IPI-549-induced changes in PI3Kγ-regulated signatures of immune suppression.
measure: Changes of Myeloid composition
time frame: 2 years
description: Compare pre- vs. post-treatment tumor tissue
measure: changes in T cell composition
time frame: 2 years
description: T cell receptor (TCR) sequencing at baseline, surgery, end of treatment or at time of disease progression.
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
time frame: 2 years
description: To determine safety and tolerability of IPI-549 and change in tumor size in patients with locally advanced HNSCC
arm group label: Arm A: IPI-549 40 mg PO qdaily
arm group type: Experimental
description: Patients enrolled in Arm A will receive IPI-549 40 mg by mouth daily for at least 14 days
intervention type: Drug
intervention name: IPI-549
description: 40mg by mouth (PO) every day (QD) for at least 14 days
arm group label: Arm A: IPI-549 40 mg PO qdaily
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ezra Cohen, MD
role: Principal Investigator
affiliation: University of California, San Diego
last name: Debanjali Ghosh, MA
phone: 858-246-0357
email: d1ghosh@health.ucsd.edu
last name: Elaine Eng
email: e1eng@ucsd.edu
facility: 
status: Recruiting
country: United States
citation: Kaneda MM, Cappello P, Nguyen AV, Ralainirina N, Hardamon CR, Foubert P, Schmid MC, Sun P, Mose E, Bouvet M, Lowy AM, Valasek MA, Sasik R, Novelli F, Hirsch E, Varner JA. Macrophage PI3Kgamma Drives Pancreatic Ductal Adenocarcinoma Progression. Cancer Discov. 2016 Aug;6(8):870-85. doi: 10.1158/2159-8290.CD-15-1346. Epub 2016 May 13.
PMID: 27179037
citation: Kaneda MM, Messer KS, Ralainirina N, Li H, Leem CJ, Gorjestani S, Woo G, Nguyen AV, Figueiredo CC, Foubert P, Schmid MC, Pink M, Winkler DG, Rausch M, Palombella VJ, Kutok J, McGovern K, Frazer KA, Wu X, Karin M, Sasik R, Cohen EE, Varner JA. PI3Kgamma is a molecular switch that controls immune suppression. Nature. 2016 Nov 17;539(7629):437-442. doi: 10.1038/nature19834. Epub 2016 Sep 19. Erratum In: Nature. 2017 Feb 2;542(7639):124.
PMID: 27642729
citation: De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell. 2013 Mar 18;23(3):277-86. doi: 10.1016/j.ccr.2013.02.013.
PMID: 23518347
citation: Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012 Mar 22;12(4):253-68. doi: 10.1038/nri3175.
PMID: 22437938
citation: Schmid MC, Avraamides CJ, Dippold HC, Franco I, Foubert P, Ellies LG, Acevedo LM, Manglicmot JR, Song X, Wrasidlo W, Blair SL, Ginsberg MH, Cheresh DA, Hirsch E, Field SJ, Varner JA. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kgamma, a single convergent point promoting tumor inflammation and progression. Cancer Cell. 2011 Jun 14;19(6):715-27. doi: 10.1016/j.ccr.2011.04.016.
PMID: 21665146
citation: Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PMID: 19097774
responsible party type: Sponsor-Investigator
investigator affiliation: University of California, San Diego
investigator full name: Ezra Cohen
investigator title: Professor of Medicine
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Neoplasms
mesh term: Head and Neck Neoplasms
mesh term: Squamous Cell Carcinoma of Head and Neck