xml: <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/NCT05988918</url>
    </required_header>
    <id_info>
      <org_study_id>UMCC 2023.005</org_study_id>
      <secondary_id>HUM00233810</secondary_id>
      <nct_id>NCT05988918</nct_id>
    </id_info>
    <brief_title>Multicenter Trial of ESK981 in Patients With Select Solid Tumors</brief_title>
    <official_title>A Phase II Multicenter Trial of ESK981 in Patients With Select Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Michigan Rogel Cancer Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </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>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This protocol will enroll patients with pancreatic adenocarcinoma and adenosquamous carcinoma&#xD;
        (Cohort 1), gastrointestinal/pancreatic neuroendocrine neoplasms with Ki-67 &gt; 20% (Cohort 2)&#xD;
        and neuroendocrine prostate carcinoma (Cohort 3)). Each cohort will have its own interim&#xD;
        analysis after enrollment of 10 patients.&#xD;
  &#xD;
        Subjects will be given a one-month (28 day) supply of study drug (ESK981). Subjects will be&#xD;
        instructed to take 4 capsules, with or without food, once per day for 5 consecutive calendar&#xD;
        days, then take a drug holiday for 2 consecutive days before repeating the 5 days on-2 days&#xD;
        off cycle in sets of 4 weeks or 28 calendar days. Subjects will be asked to keep a pill diary&#xD;
        noting the date they take their study drug.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">September 2028</completion_date>
    <primary_completion_date type="Anticipated">August 2026</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Progression Free Survival</measure>
      <time_frame>4 months after initiating study drug</time_frame>
      <description>Determining efficacy using proportion of patients alive and progression-free at 4 months within each cancer subtype</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall Response Rate (ORR) within each cancer subtype</measure>
      <time_frame>up to 18 months from treatment discontinuation</time_frame>
      <description>The ORR will be assessed per RECIST v1.1 criteria (Cohort 1 and 2) or combined RECIST v1.1 + PCWG3 criteria (Cohort 3). Partial or complete response will require confirmation on repeat scan at least 4 weeks from initial radiologic response</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DoR) within each cancer subtype</measure>
      <time_frame>up to 18 months from treatment discontinuation</time_frame>
      <description>DoR will be measured from the start date of the best response achieved until the date of relapse (i.e., progression). Continuing responders will be right-censored as of the most recent date on which their response status had been assessed. DoR applies to only the patients who achieve either a complete response or a partial response.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS) within each cancer subtype</measure>
      <time_frame>up to 18 months from treatment discontinuation</time_frame>
      <description>The OS will be defined from the date of treatment to either date of death or censoring and estimated using the product-limit method of Kaplan and Meier. Follow-up time will be censored at the date of last disease evaluation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety and tolerability in each cancer subtype</measure>
      <time_frame>up to 30 days from treatment discontinuation</time_frame>
      <description>Adverse events (AEs) will be defined per the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v5.0.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Progression- Free Survival (PFS) within each cancer subtype</measure>
      <time_frame>up to 18 months from treatment discontinuation</time_frame>
      <description>The PFS will be defined as time from date of initial treatment to date of radiological or clinical progression (leading to withdrawal from the study treatment), or death from any cause on study treatment, whichever comes first. Follow-up time will be censored at the date of last disease evaluation.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">66</enrollment>
    <condition>Pancreatic Adenocarcinoma</condition>
    <condition>Adenosquamous Carcinoma</condition>
    <condition>Pancreatic Neuroendocrine Tumor</condition>
    <condition>Pancreatic Neuroendocrine Carcinoma</condition>
    <condition>Gastrointestinal Neuroendocrine Tumor</condition>
    <condition>Gastrointestinal Neuroendocrine Carcinoma</condition>
    <condition>Neuroendocrine Prostate Carcinoma</condition>
    <arm_group>
      <arm_group_label>Cohort 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pancreatic adenocarcinoma</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pancreatic or gastrointestinal neuroendocrine neoplasms with Ki-67 &gt; 20%</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Neuroendocrine prostate carcinoma with Ki-67 &gt; 20%</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ESK981</intervention_name>
      <description>160 mg, PO, Once daily 5 days on and 2 days off</description>
      <arm_group_label>Cohort 1</arm_group_label>
      <arm_group_label>Cohort 2</arm_group_label>
      <arm_group_label>Cohort 3</arm_group_label>
      <other_name>CEP-11981</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Eligibility Criteria:&#xD;
  &#xD;
            -  Patients with histological or cytological confirmation of advanced cancer per specific&#xD;
               cohort.&#xD;
  &#xD;
                 -  Cohort 1: Pancreatic adenocarcinoma or adenosquamous carcinoma who have&#xD;
                    progressed or deemed intolerant of the standard of care chemotherapy regimens.&#xD;
  &#xD;
                 -  Cohort 2: Pancreatic or gastrointestinal neuroendocrine tumor or carcinoma with&#xD;
                    Ki-67 &gt; 20% who have progressed or deemed intolerant of at least first-line&#xD;
                    standard of care systemic therapy.&#xD;
  &#xD;
                 -  Cohort 3: The subject has histologically proven prostate cancer who have&#xD;
                    progressed or deemed intolerant of at least first-line standard of care systemic&#xD;
                    therapy with radiologic evidence of metastases and at least one of the following:&#xD;
  &#xD;
                      -  Small cell or neuroendocrine morphology on the basis of tissue sample.&#xD;
  &#xD;
                      -  Prostate adenocarcinoma with IHC staining for neuroendocrine markers (e.g.,&#xD;
                         chromogranin and synaptophysin).&#xD;
  &#xD;
                      -  Presence of visceral metastases or high-volume disease (&gt; 4 sites of&#xD;
                         metastases) with a PSA ≤ 5.&#xD;
  &#xD;
                      -  Serum chromogranin A level ≥ 5x upper limit of normal (ULN) and/or serum&#xD;
                         neuron specific enolase (NSE) ≥ 2x ULN.&#xD;
  &#xD;
                      -  Trans-differentiated carcinoma or poorly-differentiated carcinoma&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2&#xD;
  &#xD;
            -  Must be ≥ 18 years of age.&#xD;
  &#xD;
            -  Evaluable disease determined using guidelines of Response Evaluation Criteria in Solid&#xD;
               Tumors (RECIST version 1.1)&#xD;
  &#xD;
            -  Ability to understand and willingness to sign IRB-approved informed consent.&#xD;
  &#xD;
            -  Willing to provide archived tissue, if available, from a previous diagnostic biopsy.&#xD;
  &#xD;
            -  Must be able to tolerate CT and/or MRI with contrast.&#xD;
  &#xD;
            -  At least 4 weeks from major surgery with resolution of any sequela to date of&#xD;
               enrollment&#xD;
  &#xD;
            -  Laboratory values ≤2 weeks during screening must be:&#xD;
  &#xD;
                 -  Platelet count ≥ 75,000 cells/mm3&#xD;
  &#xD;
                 -  Absolute neutrophil count ≥ 1500 cells/mm3&#xD;
  &#xD;
                 -  Hemoglobin ≥ 9 g/dL&#xD;
  &#xD;
                 -  AST/ALT ≤ 3x upper limit of normal [ULN], or (≤ 5x ULN if liver metastasis&#xD;
                    present)&#xD;
  &#xD;
                 -  Bilirubin ≤ 1.5x ULN, or (≤ 2.5 x ULN for subjects with Gilbert's syndrome)&#xD;
  &#xD;
                 -  Albumin ≥ 3 g/dL&#xD;
  &#xD;
                 -  Serum creatinine clearance CrCl ≥ 50 mL/min per Cockcroft-Gault Formula&#xD;
  &#xD;
                 -  INR ≤ 1.5 (or &lt;2.0 if on anticoagulants)&#xD;
  &#xD;
            -  Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically&#xD;
               sterile) must agree to use acceptable highly effective contraceptive methods&#xD;
               (abstinence, intrauterine device [IUD], oral contraceptive(s), intrauterine hormone&#xD;
               releasing system (IUS), bilateral tubal occlusion or vasectomized partner) during and&#xD;
               for 9 months after last study dose and must have a negative serum or urine pregnancy&#xD;
               test during screening.&#xD;
  &#xD;
            -  Males with female partners (of childbearing potential) and female partners (of&#xD;
               childbearing potential) with male partners must agree to use double barrier&#xD;
               contraceptive measure (a combination of male condom with either cap, diaphragm or&#xD;
               sponge with spermicide) in addition to oral contraception, or avoidance of intercourse&#xD;
               during the study and for 6 months after last study dose is received.&#xD;
  &#xD;
            -  Female patients must not be pregnant, have a positive pregnancy test, breastfeeding or&#xD;
               planning to become pregnant or breastfeed during treatment and for an additional 9&#xD;
               months after the last dose of study treatment.&#xD;
  &#xD;
            -  Male patients must be willing to abstain from donating sperm during treatment and for&#xD;
               6 months after completion of study treatment.&#xD;
  &#xD;
            -  No evidence of active infection and no serious infection within the past 30 days.&#xD;
               Patient must have completed antibiotic course.&#xD;
  &#xD;
            -  No known cerebral metastasis, central nervous system (CNS), or epidural tumor (unless&#xD;
               previously treated, asymptomatic and stable for at least 3 months).&#xD;
  &#xD;
            -  No active heart disease including but not limited to myocardial infarction that is &lt;3&#xD;
               months prior to registration, symptomatic congestive heart failure (NYHA class 3 or&#xD;
               4), symptomatic coronary artery disease, symptomatic angina pectoris.&#xD;
  &#xD;
            -  No history of acute cerebrovascular disease, arterial embolism, pulmonary embolism,&#xD;
               percutaneous angioplasty, or coronary artery bypass surgery within 6 months prior to&#xD;
               registration.&#xD;
  &#xD;
            -  No pre-existing coagulopathy, or serious bleeding within 3 months prior to&#xD;
               registration.&#xD;
  &#xD;
            -  No prior malignancy except for the following: adequately treated basal or squamous&#xD;
               cell skin cancer, in situ cancer, localized prostate cancer (Gleason score &lt;8), or&#xD;
               adequately treated cancer from which the patient has been disease-free for at least 3&#xD;
               years prior to registration.&#xD;
  &#xD;
            -  Must not have uncontrolled diarrhea at the time of enrollment.&#xD;
  &#xD;
            -  Patients must not use a chronic daily medication known to be a strong or moderate&#xD;
               inhibitor of CYP1A2, CYP2C8 or CYP3A4 at registration (as per Appendix II).&#xD;
  &#xD;
            -  Patients must have recovered to baseline or ≤ grade 1 CTCAE v5.0 from toxicities&#xD;
               related to any prior treatments, unless adverse event(s) is deemed clinically&#xD;
               non-significant and/or stable on supportive therapy.&#xD;
  &#xD;
            -  Patients must not have uncontrolled hypertension defined as blood pressure &gt;150/90&#xD;
               despite optimal medical management.&#xD;
  &#xD;
            -  No known hypersensitivity to gelatin or lactose monohydrate.&#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>Vaibhav Sahai</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Michigan</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Cancer AnswerLine</last_name>
      <phone>1-800-865-1125</phone>
      <email>CancerAnswerLine@med.umich.edu</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 4, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 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>Carcinoma</mesh_term>
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Neuroendocrine Tumors</mesh_term>
      <mesh_term>Carcinoma, Neuroendocrine</mesh_term>
      <mesh_term>Carcinoma, Adenosquamous</mesh_term>
      <mesh_term>Carcinoma, Islet Cell</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05988918
  org study id: UMCC 2023.005
  secondary id: HUM00233810
  nct id: NCT05988918
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  This protocol will enroll patients with pancreatic adenocarcinoma and adenosquamous carcinoma
        (Cohort 1), gastrointestinal/pancreatic neuroendocrine neoplasms with Ki-67 > 20% (Cohort 2)
        and neuroendocrine prostate carcinoma (Cohort 3)). Each cohort will have its own interim
        analysis after enrollment of 10 patients.
  
        Subjects will be given a one-month (28 day) supply of study drug (ESK981). Subjects will be
        instructed to take 4 capsules, with or without food, once per day for 5 consecutive calendar
        days, then take a drug holiday for 2 consecutive days before repeating the 5 days on-2 days
        off cycle in sets of 4 weeks or 28 calendar days. Subjects will be asked to keep a pill diary
        noting the date they take their study drug.
  allocation: Non-Randomized
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression Free Survival
  time frame: 4 months after initiating study drug
  description: Determining efficacy using proportion of patients alive and progression-free at 4 months within each cancer subtype
  measure: Overall Response Rate (ORR) within each cancer subtype
  time frame: up to 18 months from treatment discontinuation
  description: The ORR will be assessed per RECIST v1.1 criteria (Cohort 1 and 2) or combined RECIST v1.1 + PCWG3 criteria (Cohort 3). Partial or complete response will require confirmation on repeat scan at least 4 weeks from initial radiologic response
  measure: Duration of Response (DoR) within each cancer subtype
  time frame: up to 18 months from treatment discontinuation
  description: DoR will be measured from the start date of the best response achieved until the date of relapse (i.e., progression). Continuing responders will be right-censored as of the most recent date on which their response status had been assessed. DoR applies to only the patients who achieve either a complete response or a partial response.
  measure: Overall Survival (OS) within each cancer subtype
  time frame: up to 18 months from treatment discontinuation
  description: The OS will be defined from the date of treatment to either date of death or censoring and estimated using the product-limit method of Kaplan and Meier. Follow-up time will be censored at the date of last disease evaluation.
  measure: Safety and tolerability in each cancer subtype
  time frame: up to 30 days from treatment discontinuation
  description: Adverse events (AEs) will be defined per the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v5.0.
  measure: Median Progression- Free Survival (PFS) within each cancer subtype
  time frame: up to 18 months from treatment discontinuation
  description: The PFS will be defined as time from date of initial treatment to date of radiological or clinical progression (leading to withdrawal from the study treatment), or death from any cause on study treatment, whichever comes first. Follow-up time will be censored at the date of last disease evaluation.
  arm group label: Cohort 1
  arm group type: Experimental
  description: Pancreatic adenocarcinoma
  arm group label: Cohort 2
  arm group type: Experimental
  description: Pancreatic or gastrointestinal neuroendocrine neoplasms with Ki-67 > 20%
  arm group label: Cohort 3
  arm group type: Experimental
  description: Neuroendocrine prostate carcinoma with Ki-67 > 20%
  intervention type: Drug
  intervention name: ESK981
  description: 160 mg, PO, Once daily 5 days on and 2 days off
  arm group label: Cohort 1
  arm group label: Cohort 2
  arm group label: Cohort 3
  other name: CEP-11981
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Vaibhav Sahai
  role: Principal Investigator
  affiliation: University of Michigan
  last name: Cancer AnswerLine
  phone: 1-800-865-1125
  email: CancerAnswerLine@med.umich.edu
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Neoplasms
  mesh term: Neuroendocrine Tumors
  mesh term: Carcinoma, Neuroendocrine
  mesh term: Carcinoma, Adenosquamous
  mesh term: Carcinoma, Islet Cell
  sharing ipd: No