<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/NCT03781986</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2018.127</org_study_id>
    <secondary_id>APG-115SG101</secondary_id>
    <secondary_id>HUM00155822</secondary_id>
    <nct_id>NCT03781986</nct_id>
  </id_info>
  <brief_title>APG-115 in Salivary Gland Cancer Trial</brief_title>
  <official_title>A Multicenter Phase I/II Trial of a Novel MDM2 Inhibitor (APG-115) in p53 Wild-type Salivary Gland Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan Rogel Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ascentage Pharma Group Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan Rogel Cancer Center</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>
      This is a phase I/II trial to evaluate the efficacy of APG-115 +/- Carboplatin for the&#xD;
      treatment p53 wild-type malignant salivary gland cancer.&#xD;
&#xD;
      Part 1 consisted of 2 arms, arm A (APG-115 monotherapy) and arm B (APG-115 + Carboplatin) and&#xD;
      was terminated early.&#xD;
&#xD;
      Part 2 is a single arm study (APG-115 monotherapy).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The current single arm study design was originally part of a study with a parallel arm given&#xD;
      combination APG-115 + Carboplatin. In the initial phase of that previous iteration, the&#xD;
      combination arm was closed early for issues related to tolerability of the combination&#xD;
      therapy. This study will continue as a single arm, monotherapy alone, Phase I/II study as&#xD;
      approved by the UM Institutional Review Board as of June 2021.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 28, 2019</start_date>
  <completion_date type="Anticipated">January 2025</completion_date>
  <primary_completion_date type="Anticipated">July 2024</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Part 1 -- Parallel assignment [terminated early]:&#xD;
Arm A: APG-115 Monotherapy&#xD;
Arm B: APG-115 + Carboplatin&#xD;
Part 2 -- Single arm (Arm A only): APG-115 Monotherapy</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Toxicity Endpoint: dose-limiting toxicity (DLT)</measure>
    <time_frame>42 days</time_frame>
    <description>DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 6 weeks (2 cycles) of study treatment. These will be assessed via CTCAE version 5.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximally tolerated dose (MTD)</measure>
    <time_frame>42 days</time_frame>
    <description>MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Overall response rate will be defined as the proportion of patients achieving either complete response (CR) or partial response (PR). Response will be assessed via RECIST v1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate by tumor histology</measure>
    <time_frame>Until death or end of study; up to approximately 5 years</time_frame>
    <description>Overall response rate will be defined as the proportion of patients achieving either complete response (CR) or partial response (PR), assessed via RECIST v1.1 and reported separately for those with histologically confirmed adenoid cystic carcinoma (ACC) versus other malignant salivary gland tumors (non-ACC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Until death or end of study; up to approximately 5 years</time_frame>
    <description>The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Until death or end of study; up to approximately 5 years</time_frame>
    <description>Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever is earlier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Until death or end of study; up to approximately 5 years</time_frame>
    <description>Overall survival (OS) is defined as the duration of time from start of treatment to time of death or end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>Until death or end of study; up to approximately 5 years</time_frame>
    <description>Defined as the proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD). Response will be assessed via RECIST v1.1</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">34</enrollment>
  <condition>Malignant Salivary Gland Cancer</condition>
  <condition>Salivary Gland Cancer</condition>
  <arm_group>
    <arm_group_label>APG-115 monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>APG-115 will be administered in an open label fashion until progression, intolerance, or patient preference.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>APG-115 + Carboplatin [terminated]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>APG-115 and Carboplatin will be administered in an open label fashion until progression, intolerance, or patient preference. [Phase 1 was terminated early and this arm was discontinued. An MTD was not established during Phase 1.]</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>APG-115</intervention_name>
    <description>APG-115 at 150mg (or lower, if dose is reduced) is taken orally every other day through day 13 of each cycle. Cycle length 21 days.</description>
    <arm_group_label>APG-115 + Carboplatin [terminated]</arm_group_label>
    <arm_group_label>APG-115 monotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin is given IV at AUC=4.5 on day 1 of each cycle. Cycle length 21 days.</description>
    <arm_group_label>APG-115 + Carboplatin [terminated]</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically documented malignant salivary gland cancers (including secretory glands&#xD;
             of the aerodigestive tract) with or without metastases, not amenable to curative&#xD;
             treatment; or there is documentation of patient refusal of curative treatment.&#xD;
&#xD;
          -  Previous mutational testing with no evidence of a p53 mutation&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1&#xD;
&#xD;
          -  Presence of measurable disease by CT scan per RECIST v1.1 with ≥ 20% increase in tumor&#xD;
             burden in the preceding 12 months&#xD;
&#xD;
          -  Life expectancy of ≥12 weeks&#xD;
&#xD;
          -  Signed and dated informed consent document indicating that the patient (or legally&#xD;
             acceptable representative) has been informed of all pertinent aspects of the trial&#xD;
             prior to enrollment&#xD;
&#xD;
          -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory&#xD;
             tests, and other study procedures&#xD;
&#xD;
          -  Patients must be able to take oral medication without breaking/opening, crushing,&#xD;
             dissolving, or chewing capsules&#xD;
&#xD;
          -  Adequate organ and marrow function obtained ≤ 2 weeks prior to enrollment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with MDM2 inhibitors&#xD;
&#xD;
          -  Patients are not eligible if they have received any systemic anti-cancer therapy&#xD;
             (including chemotherapy and/or hormone therapy) for salivary gland cancer within 4&#xD;
             weeks of the start of study therapy&#xD;
&#xD;
          -  Patients are not eligible if they have received any of the following within 4 weeks of&#xD;
             the start of study therapy: live vaccines, antiretroviral drugs&#xD;
&#xD;
          -  Progressive disease within 6 months of the last dose of platinum-based chemotherapy&#xD;
&#xD;
          -  Patients with active brain metastases are excluded because of unknown penetration into&#xD;
             the central nervous system (CNS). A confirmatory scan for asymptomatic patients is not&#xD;
             required. Patients with a history of treated CNS metastases are eligible provided they&#xD;
             meet all of the following criteria: disease outside the CNS is present, no clinical&#xD;
             evidence of progression since completion of CNS-directed therapy, minimum 4 weeks&#xD;
             between completion of radiotherapy and enrollment, and recovery from significant&#xD;
             (Grade ≥ 3) acute toxicity.&#xD;
&#xD;
          -  A serious uncontrolled medical disorder or active infection that would impair their&#xD;
             ability to receive study treatment&#xD;
&#xD;
          -  Patients (male and female) having procreative potential who are not willing or not&#xD;
             able to use 2 adequate methods of contraception or practicing abstinence during the&#xD;
             study and for 90 days following their last dose of treatment&#xD;
&#xD;
          -  Women who are pregnant or breast-feeding&#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>Paul L Swiecicki, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan Rogel Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Cancer AnswerLine</last_name>
    <phone>800-865-1125</phone>
    <email>CancerAnswerLine@med.umich.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Jameel Muzaffar, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Michigan Rogel Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cancer AnswerLine</last_name>
      <phone>800-865-1125</phone>
      <email>CancerAnswerLine@med.umich.edu</email>
    </contact>
    <investigator>
      <last_name>Paul Swiecicki, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>April 5, 2023</last_update_submitted>
  <last_update_submitted_qc>April 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>p53 wild-type</keyword>
  <keyword>Adenoid cystic carcinoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Salivary Gland Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03781986
org study id: UMCC 2018.127
secondary id: APG-115SG101
secondary id: HUM00155822
nct id: NCT03781986
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This is a phase I/II trial to evaluate the efficacy of APG-115 +/- Carboplatin for the
      treatment p53 wild-type malignant salivary gland cancer.

      Part 1 consisted of 2 arms, arm A (APG-115 monotherapy) and arm B (APG-115 + Carboplatin) and
      was terminated early.

      Part 2 is a single arm study (APG-115 monotherapy).
The current single arm study design was originally part of a study with a parallel arm given
      combination APG-115 + Carboplatin. In the initial phase of that previous iteration, the
      combination arm was closed early for issues related to tolerability of the combination
      therapy. This study will continue as a single arm, monotherapy alone, Phase I/II study as
      approved by the UM Institutional Review Board as of June 2021.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Part 1 -- Parallel assignment [terminated early]:
Arm A: APG-115 Monotherapy
Arm B: APG-115 + Carboplatin
Part 2 -- Single arm (Arm A only): APG-115 Monotherapy
primary purpose: Treatment
masking: None (Open Label)
measure: Primary Toxicity Endpoint: dose-limiting toxicity (DLT)
time frame: 42 days
description: DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 6 weeks (2 cycles) of study treatment. These will be assessed via CTCAE version 5.0
measure: Maximally tolerated dose (MTD)
time frame: 42 days
description: MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment.
measure: Overall response rate
time frame: up to 12 months
description: Overall response rate will be defined as the proportion of patients achieving either complete response (CR) or partial response (PR). Response will be assessed via RECIST v1.1.
measure: Overall response rate by tumor histology
time frame: Until death or end of study; up to approximately 5 years
description: Overall response rate will be defined as the proportion of patients achieving either complete response (CR) or partial response (PR), assessed via RECIST v1.1 and reported separately for those with histologically confirmed adenoid cystic carcinoma (ACC) versus other malignant salivary gland tumors (non-ACC)
measure: Duration of response
time frame: Until death or end of study; up to approximately 5 years
description: The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started.
measure: Progression-free survival
time frame: Until death or end of study; up to approximately 5 years
description: Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever is earlier.
measure: Overall survival
time frame: Until death or end of study; up to approximately 5 years
description: Overall survival (OS) is defined as the duration of time from start of treatment to time of death or end of study.
measure: Disease control rate
time frame: Until death or end of study; up to approximately 5 years
description: Defined as the proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD). Response will be assessed via RECIST v1.1
arm group label: APG-115 monotherapy
arm group type: Experimental
description: APG-115 will be administered in an open label fashion until progression, intolerance, or patient preference.
arm group label: APG-115 + Carboplatin [terminated]
arm group type: Experimental
description: APG-115 and Carboplatin will be administered in an open label fashion until progression, intolerance, or patient preference. [Phase 1 was terminated early and this arm was discontinued. An MTD was not established during Phase 1.]
intervention type: Drug
intervention name: APG-115
description: APG-115 at 150mg (or lower, if dose is reduced) is taken orally every other day through day 13 of each cycle. Cycle length 21 days.
arm group label: APG-115 + Carboplatin [terminated]
arm group label: APG-115 monotherapy
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin is given IV at AUC=4.5 on day 1 of each cycle. Cycle length 21 days.
arm group label: APG-115 + Carboplatin [terminated]
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paul L Swiecicki, MD
role: Principal Investigator
affiliation: University of Michigan Rogel Cancer Center
last name: Cancer AnswerLine
phone: 800-865-1125
email: CancerAnswerLine@med.umich.edu
facility: 
status: Recruiting
investigator: 
facility: 
status: Not yet recruiting
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Salivary Gland Neoplasms
mesh term: Carboplatin
sharing ipd: No