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/NCT06017323</url>
    </required_header>
    <id_info>
      <org_study_id>STUDY00001899</org_study_id>
      <nct_id>NCT06017323</nct_id>
    </id_info>
    <brief_title>Proglumide With Gemcitabine and Nab-Paclitaxel in PatientsWith Metastatic Pancreatic Ductal Adenocarcinoma</brief_title>
    <acronym>ProglumidePanc</acronym>
    <official_title>Phase I Study of Proglumide With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic DuctalAdenocarcinoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Georgetown University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Georgetown University</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 is a Phase I open labelled study to treat patients with metastatic pancreatic cancer&#xD;
        with combination therapy using standard of care first line therapy with gemcitabine and&#xD;
        nab-paclitaxel given days 1, 8, and 15 every 28 days, and proglumide. This is a phase 1 study&#xD;
        with 3+3 design, enrolling3-12 patients over 2 planned dose levels of proglumide(maximum 6&#xD;
        patients per dose level). Proglumide will be tested at the daily dose of 1200 mg orally (PO)&#xD;
        given as 400mg three times daily (TID) (dose level 1) or 1600 mg orally(PO) given as 800 mg&#xD;
        twice a day (BID) (dose level 2). All cycles are 28 days. Patients will be monitored for&#xD;
        safety and toxicity by laboratory blood testing and physical examinations.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">July 2026</completion_date>
    <primary_completion_date type="Anticipated">July 2026</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Proglumide Recommended Phase II dose and schedule (RP2D)</measure>
      <time_frame>2 years</time_frame>
      <description>Determination of the recommended phase II dose and schedule (RP2D) of proglumide in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>through 2 years after end of treatment</time_frame>
      <description>median overall survival will be estimated using Kaplan-Meier curves.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival</measure>
      <time_frame>2 years</time_frame>
      <description>median progression free survival will be estimated using Kaplan-Meier curves.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective response rate by RECIST v. 1.1</measure>
      <time_frame>2 years</time_frame>
      <description>Every 8 weeks (± 7 days) radiographic imaging (CT or MRI) will be done to assess tumor burden according to RECIST v. 1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in tumor marker (CA19-9)</measure>
      <time_frame>2 years</time_frame>
      <description>Maximum percent decrease in CA19-9 will be analyzed.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">12</enrollment>
    <condition>Metastatic Pancreatic Cancer</condition>
    <arm_group>
      <arm_group_label>Dose Level 1:Proglumide TID with Gemcitabine and Nab-Paclitaxel</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Proglumide given three times a day with gemcitabine and nab-paclitaxel</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose Level 2:Proglumide BID with Gemcitabine and Nab-Paclitaxel</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Proglumide given two times a day with gemcitabine and nab-paclitaxel</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Gemcitabine</intervention_name>
      <description>1000mg/m2 IV given days 1, 8, and 15every 28 days (1 cycle)</description>
      <arm_group_label>Dose Level 1:Proglumide TID with Gemcitabine and Nab-Paclitaxel</arm_group_label>
      <arm_group_label>Dose Level 2:Proglumide BID with Gemcitabine and Nab-Paclitaxel</arm_group_label>
      <other_name>Gemzar</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Nab paclitaxel</intervention_name>
      <description>125 mg/m2 given days 1, 8, and 15every 28 days (1 cycle)</description>
      <arm_group_label>Dose Level 1:Proglumide TID with Gemcitabine and Nab-Paclitaxel</arm_group_label>
      <arm_group_label>Dose Level 2:Proglumide BID with Gemcitabine and Nab-Paclitaxel</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Proglumide Dose level 1</intervention_name>
      <description>Daily dose of 1200 mg orally given as400 mg orally (PO), three times a day(TID) (dose level 1)</description>
      <arm_group_label>Dose Level 1:Proglumide TID with Gemcitabine and Nab-Paclitaxel</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Proglumide Dose level 2</intervention_name>
      <description>Daily dose of 1600 mg orally given as800 mg orally (PO) twice a day (BID)(dose level 2).</description>
      <arm_group_label>Dose Level 2:Proglumide BID with Gemcitabine and Nab-Paclitaxel</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Written informed consent and any locally-required authorization (e.g., HIPAA in the&#xD;
               USA) obtained from the patient prior to performing any protocol-related procedures,&#xD;
               including screening evaluations&#xD;
  &#xD;
            2. Age &gt; 18 years at time of study entry.&#xD;
  &#xD;
            3. Adequate normal organ and marrow function as defined below:&#xD;
  &#xD;
                 -  Hemoglobin ≥ 9.0 g/dL&#xD;
  &#xD;
                 -  Absolute neutrophil count (ANC) &gt; 1500 permm3&#xD;
  &#xD;
                 -  Platelet count ≥100,000 per mm3)&#xD;
  &#xD;
                 -  Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).&#xD;
  &#xD;
                 -  Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤2.5 x ULN of&#xD;
                    normal unless liver metastases are present, in which case it must be ≤5x ULN&#xD;
  &#xD;
                 -  Creatinine clearance (CL) &gt;60 mL/min using the Cockcroft-Gault formula.&#xD;
  &#xD;
            4. Evidence of post-menopausal status or negative urine or serum pregnancy test for&#xD;
               female pre-menopausal patients. Women will be considered post-menopausal if they have&#xD;
               been amenorrheic for 12 months without an alternative medical cause. The following&#xD;
               age-specific requirements apply:&#xD;
  &#xD;
               -Women &lt;50 years of age would be considered post-menopausal if they have been&#xD;
               amenorrheic for 12 months or more following cessation of exogenous hormonal&#xD;
               treatments, or if they have luteinizing hormone and follicle-stimulating hormone&#xD;
               levels in the post-menopausal range for the institution or underwent surgical&#xD;
               sterilization(bilateral oophorectomy or hysterectomy).&#xD;
  &#xD;
            5. Patients must have measurable disease by RECIST v1.1 and disease amenable to serial&#xD;
               biopsy.&#xD;
  &#xD;
            6. Subjects may not have received prior therapy with Gemcitabine (GEM)/Nab-paclitaxel&#xD;
               (NAB-P).&#xD;
  &#xD;
            7. Patients must have metastatic pancreatic ductal adenocarcinoma with adenocarcinoma as&#xD;
               the dominant histology (biopsy-proven, primary tumor biopsy is acceptable for&#xD;
               eligibility)&#xD;
  &#xD;
            8. No prior systemic treatment for metastatic disease(neoadjuvant/adjuvant therapy is&#xD;
               allowable but could not contain GEM or NAB-P).&#xD;
  &#xD;
            9. Patient is willing and able to comply with the protocol for the duration of the study&#xD;
               including undergoing treatment and scheduled visits and examinations including follow&#xD;
               up.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Subjects with a concurrent malignancy or malignancy within 3 years prior to starting&#xD;
               study drug, with the exception of adequately treated basal or squamous cell carcinoma,&#xD;
               non-melanomatous skin cancer or curatively resected cervical cancer, or localized&#xD;
               prostate cancer following definitive therapy.&#xD;
  &#xD;
            2. Subjects with uncontrolled cardiovascular diseases(congestive heart failure, symptoms&#xD;
               of coronary artery disease, cardiac arrhythmias) or who have suffered a myocardial&#xD;
               infarction in the preceding 6months.&#xD;
  &#xD;
            3. Blood anticoagulation that cannot be safely stopped for biopsy.&#xD;
  &#xD;
            4. Subjects with poorly controlled medical conditions including asthma, chronic&#xD;
               obstructive pulmonary disease, diabetes, seizure disorders, hepatic or renal failure.&#xD;
  &#xD;
            5. Pregnant or nursing women.&#xD;
  &#xD;
            6. Men or women of childbearing potential who are unwilling to employ adequate&#xD;
               contraception(condoms, diaphragm, birth control pills, injections, intrauterine device&#xD;
               [IUD], or abstinence) prior to study entry, for the duration of study participation,&#xD;
               and for 6 months thereafter.&#xD;
  &#xD;
            7. Any concurrent chemotherapy, Investigational Product (IP), biologic, or hormonal&#xD;
               therapy for cancer treatment.&#xD;
  &#xD;
            8. Major surgical procedure (as defined by the Investigator) within 28 days prior to the&#xD;
               first dose of IP. Note: Local surgery of isolated lesions for palliative intent is&#xD;
               acceptable.&#xD;
  &#xD;
            9. History of allogenic organ transplantation.&#xD;
  &#xD;
           10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active&#xD;
               infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable&#xD;
               angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic&#xD;
               gastrointestinal conditions associated with diarrhea or inability to digest and absorb&#xD;
               pills, or psychiatric illness/social situations that would limit compliance with study&#xD;
               requirement, substantially increase risk of incurring Adverse Events (AEs) or&#xD;
               compromise the ability of the patient to give written informed consent&#xD;
  &#xD;
           11. Active infection including tuberculosis (clinical evaluation that includes clinical&#xD;
               history, physical examination and radiographic findings, and Tuberculosis (TB) testing&#xD;
               in line with local practice), hepatitis B (HBV) (known positive HBV surface antigen&#xD;
               (HBsAg) result), hepatitis C (HCV), or human immunodeficiency virus (positive HIV 1/2&#xD;
               antibodies).&#xD;
  &#xD;
                 -  Patients with a past or resolved HBV infection(defined as the presence of&#xD;
                    hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.&#xD;
  &#xD;
                 -  Patients positive for hepatitis C (HCV)antibody are eligible only if polymerase&#xD;
                    chain reaction is negative for HCV RNA.&#xD;
  &#xD;
                 -  Testing for tuberculosis, hepatitis B and C and HIV is not a requirement for&#xD;
                    screening for the clinical trial.&#xD;
  &#xD;
           12. Receipt of live attenuated vaccine within 30 days prior to the first dose of&#xD;
               investigational drug. Note: Patients, if enrolled, should not receive live vaccine&#xD;
               while receiving IP and up to 30 days after the last dose of IP.&#xD;
  &#xD;
           13. Female patients who are pregnant or breastfeeding or male or female patients of&#xD;
               reproductive potential who are not willing to employ effective birth control from&#xD;
               screening to 90 days after the last dose of proglumide therapy.&#xD;
  &#xD;
           14. Known allergy or hypersensitivity to any of the study drugs or any of the study drug&#xD;
               excipients.&#xD;
  &#xD;
           15. Patient is unable to swallow pills or has a malabsorption syndrome that would not&#xD;
               enable the patient to properly absorb proglumide.&#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>Benjamin WE, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Georgetown University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Nicole Swanson</last_name>
      <phone>202-687-9194</phone>
      <email>ns1209@georgetown.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Lombardi Comprehensive Cancer Center, Georgetown University</name>
        <address>
          <city>Washington</city>
          <state>District of Columbia</state>
          <zip>20007</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>September 15, 2023</last_update_submitted>
    <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Proglumide</keyword>
    <keyword>Pancreatic Cancer</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pancreatic Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Paclitaxel</mesh_term>
      <mesh_term>Gemcitabine</mesh_term>
      <mesh_term>Proglumide</mesh_term>
    </intervention_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/NCT06017323
  org study id: STUDY00001899
  nct id: NCT06017323
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a Phase I open labelled study to treat patients with metastatic pancreatic cancer
        with combination therapy using standard of care first line therapy with gemcitabine and
        nab-paclitaxel given days 1, 8, and 15 every 28 days, and proglumide. This is a phase 1 study
        with 3+3 design, enrolling3-12 patients over 2 planned dose levels of proglumide(maximum 6
        patients per dose level). Proglumide will be tested at the daily dose of 1200 mg orally (PO)
        given as 400mg three times daily (TID) (dose level 1) or 1600 mg orally(PO) given as 800 mg
        twice a day (BID) (dose level 2). All cycles are 28 days. Patients will be monitored for
        safety and toxicity by laboratory blood testing and physical examinations.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Proglumide Recommended Phase II dose and schedule (RP2D)
  time frame: 2 years
  description: Determination of the recommended phase II dose and schedule (RP2D) of proglumide in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma
  measure: Overall survival (OS)
  time frame: through 2 years after end of treatment
  description: median overall survival will be estimated using Kaplan-Meier curves.
  measure: Progression-free survival
  time frame: 2 years
  description: median progression free survival will be estimated using Kaplan-Meier curves.
  measure: Objective response rate by RECIST v. 1.1
  time frame: 2 years
  description: Every 8 weeks (± 7 days) radiographic imaging (CT or MRI) will be done to assess tumor burden according to RECIST v. 1.1
  measure: Change in tumor marker (CA19-9)
  time frame: 2 years
  description: Maximum percent decrease in CA19-9 will be analyzed.
  arm group label: Dose Level 1:Proglumide TID with Gemcitabine and Nab-Paclitaxel
  arm group type: Experimental
  description: Proglumide given three times a day with gemcitabine and nab-paclitaxel
  arm group label: Dose Level 2:Proglumide BID with Gemcitabine and Nab-Paclitaxel
  arm group type: Experimental
  description: Proglumide given two times a day with gemcitabine and nab-paclitaxel
  intervention type: Drug
  intervention name: Gemcitabine
  description: 1000mg/m2 IV given days 1, 8, and 15every 28 days (1 cycle)
  arm group label: Dose Level 1:Proglumide TID with Gemcitabine and Nab-Paclitaxel
  arm group label: Dose Level 2:Proglumide BID with Gemcitabine and Nab-Paclitaxel
  other name: Gemzar
  intervention type: Drug
  intervention name: Nab paclitaxel
  description: 125 mg/m2 given days 1, 8, and 15every 28 days (1 cycle)
  arm group label: Dose Level 1:Proglumide TID with Gemcitabine and Nab-Paclitaxel
  arm group label: Dose Level 2:Proglumide BID with Gemcitabine and Nab-Paclitaxel
  intervention type: Drug
  intervention name: Proglumide Dose level 1
  description: Daily dose of 1200 mg orally given as400 mg orally (PO), three times a day(TID) (dose level 1)
  arm group label: Dose Level 1:Proglumide TID with Gemcitabine and Nab-Paclitaxel
  intervention type: Drug
  intervention name: Proglumide Dose level 2
  description: Daily dose of 1600 mg orally given as800 mg orally (PO) twice a day (BID)(dose level 2).
  arm group label: Dose Level 2:Proglumide BID with Gemcitabine and Nab-Paclitaxel
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Benjamin WE, MD
  role: Principal Investigator
  affiliation: Georgetown University
  last name: Nicole Swanson
  phone: 202-687-9194
  email: ns1209@georgetown.edu
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: Pancreatic Neoplasms
  mesh term: Paclitaxel
  mesh term: Gemcitabine
  mesh term: Proglumide
  sharing ipd: No