<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/NCT04439188</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2020-03143</org_study_id>
    <secondary_id>NCI-2020-03143</secondary_id>
    <secondary_id>EAY131-P</secondary_id>
    <secondary_id>EAY131-P</secondary_id>
    <secondary_id>U10CA180820</secondary_id>
    <secondary_id>U24CA196172</secondary_id>
    <nct_id>NCT04439188</nct_id>
  </id_info>
  <brief_title>Testing GSK2636771 as a Potential Targeted Treatment in Cancers With PTEN Loss of Expression (MATCH-Subprotocol P)</brief_title>
  <official_title>MATCH Treatment Subprotocol P: Phase II Study of PI3K Beta Specific Inhibitor, GSK2636771, in Patients With Tumors With PTEN Loss by IHC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II MATCH treatment trial identifies the effects of GSK2636771 in patients whose&#xD;
      cancer has a complete loss of PTEN expression. GSK2636771 may block a protein called&#xD;
      PI3K-beta, which may be needed for growth of cancer cells with complete loss of PTEN&#xD;
      expression. Researchers hope to learn if GSK2636771 will shrink this type of cancer or stop&#xD;
      its growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the proportion of patients with objective response (OR) to targeted study&#xD;
      agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the proportion of patients alive and progression free at 6 months of treatment&#xD;
      with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple&#xD;
      myeloma.&#xD;
&#xD;
      II. To evaluate time until death or disease progression. III. To identify potential&#xD;
      predictive biomarkers beyond the genomic alteration by which treatment is assigned or&#xD;
      resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and&#xD;
      imaging-based assessment platforms.&#xD;
&#xD;
      IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes&#xD;
      from pre- through post-therapy imaging can predict objective response and progression free&#xD;
      survival and to evaluate the association between pre-treatment radiomic phenotypes and&#xD;
      targeted gene mutation patterns of tumor biopsy specimens.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive PI3K-beta inhibitor GSK2636771 (GSK2636771) orally (PO) once daily (QD) on&#xD;
      days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months if less than 2&#xD;
      years from study entry, and then every 6 months for year 3 from study entry.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 25, 2016</start_date>
  <primary_completion_date type="Anticipated">November 30, 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>Objective response rate (ORR)</measure>
    <time_frame>Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration</time_frame>
    <description>ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Assessed every 3 months for =&lt; 2 years and every 6 months for year 3</time_frame>
    <description>OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration</time_frame>
    <description>Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">35</enrollment>
  <condition>Advanced Lymphoma</condition>
  <condition>Advanced Malignant Solid Neoplasm</condition>
  <condition>Hematopoietic and Lymphoid Cell Neoplasm</condition>
  <condition>Refractory Lymphoma</condition>
  <condition>Refractory Malignant Solid Neoplasm</condition>
  <condition>Refractory Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Treatment (GSK2636771)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PI3K-beta Inhibitor GSK2636771</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (GSK2636771)</arm_group_label>
    <other_name>GSK-2636771</other_name>
    <other_name>GSK2636771</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have met applicable eligibility criteria in the Master MATCH Protocol&#xD;
             prior to registration to treatment subprotocol&#xD;
&#xD;
          -  Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment&#xD;
             assignment and must have no clinically important abnormalities in rhythm, conduction&#xD;
             or morphology of resting ECG (e.g. complete left bundle branch block, third degree&#xD;
             heart block)&#xD;
&#xD;
          -  Patients must have complete loss of cytoplasmic and nuclear PTEN staining on&#xD;
             immunohistochemistry as determined by the MATCH PTEN immunohistochemistry (IHC) assay&#xD;
             performed at MD Anderson. Patients can have any PTEN mutation or deletion status, but&#xD;
             MUST have PTEN loss by IHC&#xD;
&#xD;
          -  Patients must have hemoglobin &gt;= 9 g/dL&#xD;
&#xD;
          -  Patients must have a serum creatinine that is &lt; 1.5 x upper limit of normal (ULN) or&#xD;
             have a 24-hour creatinine clearance of &gt; 50 mL/min&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients must not have known hypersensitivity to GSK2636771 or compounds of similar&#xD;
             chemical or biologic composition&#xD;
&#xD;
          -  Patients must not have tumors harboring co-existing aberrations activating the&#xD;
             PI3K/MTOR and MAPK pathways, such as PIK3CA, PIK3R1, BRAF, KRAS and AKT1, TSC1/2,&#xD;
             mTOR, NF2, NRAS, HRAS, NF1&#xD;
&#xD;
          -  Patients must not have received prior treatment with agents targeting the PI3K beta,&#xD;
             AKT, or mTOR:&#xD;
&#xD;
               -  This includes (but is not limited to):&#xD;
&#xD;
                    -  mTOR inhibitors: temsirolimus, everolimus, ridaforolimus, sirolimus,&#xD;
                       salirasib, CC-223, INK128, DS-3078, CC-115, AZD-2014&#xD;
&#xD;
               -  Dual PI3K/mTOR inhibitors: BEZ235, XL-765, GDC 0980, PF-04691502, GSK 2126458,&#xD;
                  Quinacrine, PKI-587, P-P7170, LY3023414, GDC 0084, DS 7423, CBLC-137&#xD;
&#xD;
                    -  Pan-PI3K inhibitors: BKM-120 (buparlisib), PX-866, XL-147, GDC-0941&#xD;
                       (pictilisib), BAY-806946, ZSTK-474, WX 037, SRX5000, SRX2523, AMG511,&#xD;
                       PQR308, BAY 94-9343&#xD;
&#xD;
                    -  PI3K inhibitors with beta isoform activity: prior GSK2636771 is not allowed,&#xD;
                       nor is GS-9820, PQR3XX, KAR4139&#xD;
&#xD;
               -  The following previous treatments are allowed:&#xD;
&#xD;
                    -  BYL719 (PI3Kalpha inhibitor)&#xD;
&#xD;
                    -  GDC-0032 (PI3Kalpha inhibitor)&#xD;
&#xD;
                    -  INK1117 (PI3Kalpha inhibitor)&#xD;
&#xD;
                    -  Idelalisib (PI3Kdelta inhibitor)&#xD;
&#xD;
                    -  IPI-125 (PI3K gamma delta inhibitor)&#xD;
&#xD;
                    -  TGR1202 (PI3Kdelta inhibitor)&#xD;
&#xD;
                    -  SRX2558 (PI3Kdelta inhibitor)&#xD;
&#xD;
                    -  RP6530 (PI3K gamma delta inhibitor)&#xD;
&#xD;
                    -  PWT143 (PI3Kdelta inhibitor)&#xD;
&#xD;
                    -  IPI443 (PI3K gamma delta inhibitor)&#xD;
&#xD;
                    -  GNE293 (PI3Kdelta inhibitor)&#xD;
&#xD;
          -  Patients with a history of interstitial lung disease or pneumonitis are excluded&#xD;
&#xD;
          -  Patients must not have any congenital platelet function defects and cannot be on any&#xD;
             of the following anti-platelet drugs: clopidogrel, ticlopidine, prasugrel, that act at&#xD;
             platelet purinergic receptors&#xD;
&#xD;
               -  Any need for starting anti-platelet therapy in a patient enrolled to this arm&#xD;
                  will have to be evaluated by the subprotocol chair&#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>Filip Janku</last_name>
    <role>Principal Investigator</role>
    <affiliation>ECOG-ACRIN Cancer Research Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ECOG-ACRIN Cancer Research Group</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19103</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>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>June 6, 2023</last_update_submitted>
  <last_update_submitted_qc>June 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2023</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>Neoplasms</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>GSK2636771</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 6, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT04439188/Prot_001.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/NCT04439188
org study id: NCI-2020-03143
secondary id: NCI-2020-03143
secondary id: EAY131-P
secondary id: EAY131-P
secondary id: U10CA180820
secondary id: U24CA196172
nct id: NCT04439188
lead sponsor: 
has dmc: Yes
This phase II MATCH treatment trial identifies the effects of GSK2636771 in patients whose
      cancer has a complete loss of PTEN expression. GSK2636771 may block a protein called
      PI3K-beta, which may be needed for growth of cancer cells with complete loss of PTEN
      expression. Researchers hope to learn if GSK2636771 will shrink this type of cancer or stop
      its growth.
PRIMARY OBJECTIVE:

      I. To evaluate the proportion of patients with objective response (OR) to targeted study
      agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

      SECONDARY OBJECTIVES:

      I. To evaluate the proportion of patients alive and progression free at 6 months of treatment
      with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple
      myeloma.

      II. To evaluate time until death or disease progression. III. To identify potential
      predictive biomarkers beyond the genomic alteration by which treatment is assigned or
      resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and
      imaging-based assessment platforms.

      IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes
      from pre- through post-therapy imaging can predict objective response and progression free
      survival and to evaluate the association between pre-treatment radiomic phenotypes and
      targeted gene mutation patterns of tumor biopsy specimens.

      OUTLINE:

      Patients receive PI3K-beta inhibitor GSK2636771 (GSK2636771) orally (PO) once daily (QD) on
      days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up every 3 months if less than 2
      years from study entry, and then every 6 months for year 3 from study entry.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
description: ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.
measure: Overall survival (OS)
time frame: Assessed every 3 months for =< 2 years and every 6 months for year 3
description: OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.
measure: Progression free survival (PFS)
time frame: Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
description: Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.
arm group label: Treatment (GSK2636771)
arm group type: Experimental
description: Patients receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: PI3K-beta Inhibitor GSK2636771
description: Given PO
arm group label: Treatment (GSK2636771)
other name: GSK-2636771
other name: GSK2636771
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Filip Janku
role: Principal Investigator
affiliation: ECOG-ACRIN Cancer Research Group
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Neoplasms
mesh term: Multiple Myeloma
mesh term: GSK2636771
provided document: 