<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/NCT01660971</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2012-01290</org_study_id>
    <secondary_id>NCI-2012-01290</secondary_id>
    <secondary_id>VICCGI1173</secondary_id>
    <secondary_id>GI 1173</secondary_id>
    <secondary_id>CDR0000738551</secondary_id>
    <secondary_id>GI 1173</secondary_id>
    <secondary_id>9043</secondary_id>
    <secondary_id>P30CA068485</secondary_id>
    <nct_id>NCT01660971</nct_id>
  </id_info>
  <brief_title>Gemcitabine Hydrochloride, Dasatinib, and Erlotinib Hydrochloride in Treating Patients With Pancreatic Cancer That Is Metastatic or Cannot Be Removed by Surgery</brief_title>
  <official_title>A Phase 1 Study of Gemcitabine, Dasatinib and Erlotinib in Patients With Advanced Pancreatic Carcinoma</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>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of gemcitabine hydrochloride and&#xD;
      dasatinib when given together with erlotinib hydrochloride in treating patients with&#xD;
      pancreatic cancer that has spread to other places in the body or cannot be removed by&#xD;
      surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different&#xD;
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from&#xD;
      dividing. Dasatinib and erlotinib hydrochloride may stop the growth of tumor cells by&#xD;
      blocking some of the enzymes needed for cell growth. Giving gemcitabine hydrochloride and&#xD;
      dasatinib together with erlotinib hydrochloride may kill more tumor cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the maximum tolerated dose (also phase II recommended dose) of the&#xD;
      combination of gemcitabine (gemcitabine hydrochloride), erlotinib (erlotinib hydrochloride)&#xD;
      and dasatinib in patients with advanced pancreatic adenocarcinoma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the safety profile of the combination of gemcitabine, erlotinib and&#xD;
      dasatinib.&#xD;
&#xD;
      II. To evaluate the response rate and response duration of advanced pancreatic adenocarcinoma&#xD;
      treated with dasatinib, erlotinib and gemcitabine.&#xD;
&#xD;
      III. To determine progression-free survival and overall survival for this group of patients.&#xD;
&#xD;
      IV. To determine the utility of advanced magnetic resonance imaging techniques to assess in&#xD;
      vivo effects of therapy (changes in tumor vascularity, cellularity).&#xD;
&#xD;
      V. To assess the use of serum markers as predictors of response and outcome.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of gemcitabine hydrochloride and dasatinib.&#xD;
&#xD;
      Patients receive gemcitabine hydrochloride intravenously (IV) over 30-60 minutes on days 1,&#xD;
      8, and 15, and dasatinib orally (PO) once daily (QD) and erlotinib hydrochloride PO QD on&#xD;
      days 1-28. Courses 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 for 30 days and then every 4&#xD;
      weeks thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 30, 2012</start_date>
  <primary_completion_date type="Actual">September 6, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <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>Maximum tolerated dose of gemcitabine hydrochloride and dasatinib given together with erlotinib hydrochloride, determined by incidence of dose-limiting toxicity graded according to NCI CTCAE v 4.0</measure>
    <time_frame>Up to 4 weeks after completion of study treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>The time from enrollment until the time of death due to any cause, assessed up to 6 years</time_frame>
    <description>The OS curves will be estimated by the Kaplan-Meier method. Median OS and its 95% confidence intervals will be estimated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>The time from enrollment until the first occurrence of radiographic or clinical evidence of disease progression or death due to any cause, assessed up to 6 years</time_frame>
    <description>The PFS curves will be estimated by the Kaplan-Meier method. Median PFS and its 95% confidence intervals will be estimated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate, assessed according to RECIST</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The response rate and its 95% confidence interval will be calculated using the exact binominal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response duration</measure>
    <time_frame>The time from when measurement criteria are met for complete response or partial response (whichever is first recorded) until the date that recurrent or progressive disease is objectively documented, assessed up to 6 years</time_frame>
    <description>The response duration for the responders will be summarized using mean, median and standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious and other significant adverse events (AEs), graded according to NCI CTCAE v 4.0</measure>
    <time_frame>Up to 30 days after completion of study treatment</time_frame>
    <description>The patient incidence of AEs will be summarized by preferred term, severity and relationship to study drug. Cross tabulations will be provided to summarize frequencies of abnormalities.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Metastatic Pancreatic Adenocarcinoma</condition>
  <condition>Recurrent Pancreatic Carcinoma</condition>
  <condition>Stage III Pancreatic Cancer AJCC v6 and v7</condition>
  <condition>Stage IV Pancreatic Cancer AJCC v6 and v7</condition>
  <arm_group>
    <arm_group_label>Treatment (gemcitabine, dasatinib, erlotinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1, 8, and 15, and dasatinib PO QD and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dasatinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (gemcitabine, dasatinib, erlotinib)</arm_group_label>
    <other_name>BMS-354825</other_name>
    <other_name>Dasatinib Hydrate</other_name>
    <other_name>Dasatinib Monohydrate</other_name>
    <other_name>Sprycel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Erlotinib Hydrochloride</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (gemcitabine, dasatinib, erlotinib)</arm_group_label>
    <other_name>CP-358</other_name>
    <other_name>Cp-358,774</other_name>
    <other_name>OSI-774</other_name>
    <other_name>Tarceva</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine Hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (gemcitabine, dasatinib, erlotinib)</arm_group_label>
    <other_name>dFdCyd</other_name>
    <other_name>Difluorodeoxycytidine Hydrochloride</other_name>
    <other_name>Gemcitabine HCI</other_name>
    <other_name>Gemzar</other_name>
    <other_name>LY-188011</other_name>
    <other_name>LY188011</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cytologically or histologically confirmed pancreatic adenocarcinoma (excluding islet&#xD;
             cell or ampullary tumors) that is metastatic or unresectable&#xD;
&#xD;
          -  Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)&#xD;
             1.1&#xD;
&#xD;
          -  Patients may have received prior chemotherapy for advanced disease as long as it did&#xD;
             not include gemcitabine; if patients received prior adjuvant therapy including&#xD;
             gemcitabine, patients must be &gt; 6 months from the last dose of gemcitabine; patients&#xD;
             must have recovered from side effects of prior therapy to grade =&lt; 1 as measured by&#xD;
             National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)&#xD;
             version (v) 4.0&#xD;
&#xD;
          -  Patients may have received prior radiation presuming &gt; 4 weeks since last dose and&#xD;
             measurable disease outside the radiation field&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 1&#xD;
&#xD;
          -  Anticipated life expectancy of greater than 3 months&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/mcL&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/mcL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  Total bilirubin &lt; 2.5 x institutional upper limit of normal (ULN)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic pyruvate transaminase [SGOT])/alanine&#xD;
             aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =&lt; 2.5 x&#xD;
             institutional upper limit of normal OR =&lt; 5 x institutional upper limit of normal when&#xD;
             liver metastases are present&#xD;
&#xD;
          -  Creatinine within normal institutional limits OR creatinine clearance &gt;= 60&#xD;
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for&#xD;
             the duration of study participation; should a woman become pregnant or suspect she is&#xD;
             pregnant while participating in this study, she should inform her treating physician&#xD;
             immediately&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
          -  Patients must be able to swallow pills&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for&#xD;
             nitrosoureas or mitomycin C) prior to entering the study or those who have not&#xD;
             recovered from adverse events due to agents administered more than 4 weeks earlier&#xD;
             (with the exception of alopecia and neuropathy); no radiation is allowed on study&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents&#xD;
&#xD;
          -  Major surgical procedure within 4 weeks of treatment&#xD;
&#xD;
          -  Patients with known brain metastases&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to dasatinib, erlotinib or gemcitabine&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  Pregnant women are excluded from this study, breastfeeding should be discontinued if&#xD;
             the mother is treated with erlotinib or dasatinib&#xD;
&#xD;
          -  Patients with immune deficiency are excluded&#xD;
&#xD;
          -  Patients on potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)&#xD;
             inducers and inhibitors&#xD;
&#xD;
          -  Malabsorption syndrome or other condition that would interfere with intestinal&#xD;
             absorption&#xD;
&#xD;
          -  Other active malignancy (with the exception of locally treated non-melanoma skin&#xD;
             cancers)&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV) positive patients who are on combination&#xD;
             antiretroviral therapy&#xD;
&#xD;
          -  Patients may not have any clinically significant cardiovascular disease including the&#xD;
             following:&#xD;
&#xD;
               -  Myocardial infarction or ventricular tachyarrhythmia within 6 months&#xD;
&#xD;
               -  Prolonged corrected QT (QTc) &gt; 480 msec (Fridericia correction)&#xD;
&#xD;
               -  Known ejection faction less than institutional normal&#xD;
&#xD;
               -  Major conduction abnormality (unless a cardiac pacemaker is present)&#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>Dana B Cardin</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University/Ingram Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University/Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 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>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Erlotinib Hydrochloride</mesh_term>
    <mesh_term>Dasatinib</mesh_term>
  </intervention_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/NCT01660971
org study id: NCI-2012-01290
secondary id: NCI-2012-01290
secondary id: VICCGI1173
secondary id: GI 1173
secondary id: CDR0000738551
secondary id: GI 1173
secondary id: 9043
secondary id: P30CA068485
nct id: NCT01660971
lead sponsor: 
This phase I trial studies the side effects and best dose of gemcitabine hydrochloride and
      dasatinib when given together with erlotinib hydrochloride in treating patients with
      pancreatic cancer that has spread to other places in the body or cannot be removed by
      surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Dasatinib and erlotinib hydrochloride may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth. Giving gemcitabine hydrochloride and
      dasatinib together with erlotinib hydrochloride may kill more tumor cells.
PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (also phase II recommended dose) of the
      combination of gemcitabine (gemcitabine hydrochloride), erlotinib (erlotinib hydrochloride)
      and dasatinib in patients with advanced pancreatic adenocarcinoma.

      SECONDARY OBJECTIVES:

      I. To determine the safety profile of the combination of gemcitabine, erlotinib and
      dasatinib.

      II. To evaluate the response rate and response duration of advanced pancreatic adenocarcinoma
      treated with dasatinib, erlotinib and gemcitabine.

      III. To determine progression-free survival and overall survival for this group of patients.

      IV. To determine the utility of advanced magnetic resonance imaging techniques to assess in
      vivo effects of therapy (changes in tumor vascularity, cellularity).

      V. To assess the use of serum markers as predictors of response and outcome.

      OUTLINE: This is a dose-escalation study of gemcitabine hydrochloride and dasatinib.

      Patients receive gemcitabine hydrochloride intravenously (IV) over 30-60 minutes on days 1,
      8, and 15, and dasatinib orally (PO) once daily (QD) and erlotinib hydrochloride PO QD on
      days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up for 30 days and then every 4
      weeks thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose of gemcitabine hydrochloride and dasatinib given together with erlotinib hydrochloride, determined by incidence of dose-limiting toxicity graded according to NCI CTCAE v 4.0
time frame: Up to 4 weeks after completion of study treatment
measure: Overall survival (OS)
time frame: The time from enrollment until the time of death due to any cause, assessed up to 6 years
description: The OS curves will be estimated by the Kaplan-Meier method. Median OS and its 95% confidence intervals will be estimated.
measure: Progression free survival (PFS)
time frame: The time from enrollment until the first occurrence of radiographic or clinical evidence of disease progression or death due to any cause, assessed up to 6 years
description: The PFS curves will be estimated by the Kaplan-Meier method. Median PFS and its 95% confidence intervals will be estimated.
measure: Response rate, assessed according to RECIST
time frame: Up to 6 years
description: The response rate and its 95% confidence interval will be calculated using the exact binominal method.
measure: Response duration
time frame: The time from when measurement criteria are met for complete response or partial response (whichever is first recorded) until the date that recurrent or progressive disease is objectively documented, assessed up to 6 years
description: The response duration for the responders will be summarized using mean, median and standard deviation.
measure: Serious and other significant adverse events (AEs), graded according to NCI CTCAE v 4.0
time frame: Up to 30 days after completion of study treatment
description: The patient incidence of AEs will be summarized by preferred term, severity and relationship to study drug. Cross tabulations will be provided to summarize frequencies of abnormalities.
arm group label: Treatment (gemcitabine, dasatinib, erlotinib)
arm group type: Experimental
description: Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1, 8, and 15, and dasatinib PO QD and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Dasatinib
description: Given PO
arm group label: Treatment (gemcitabine, dasatinib, erlotinib)
other name: BMS-354825
other name: Dasatinib Hydrate
other name: Dasatinib Monohydrate
other name: Sprycel
intervention type: Drug
intervention name: Erlotinib Hydrochloride
description: Given PO
arm group label: Treatment (gemcitabine, dasatinib, erlotinib)
other name: CP-358
other name: Cp-358,774
other name: OSI-774
other name: Tarceva
intervention type: Drug
intervention name: Gemcitabine Hydrochloride
description: Given IV
arm group label: Treatment (gemcitabine, dasatinib, erlotinib)
other name: dFdCyd
other name: Difluorodeoxycytidine Hydrochloride
other name: Gemcitabine HCI
other name: Gemzar
other name: LY-188011
other name: LY188011
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dana B Cardin
role: Principal Investigator
affiliation: Vanderbilt University/Ingram Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Pancreatic Neoplasms
mesh term: Gemcitabine
mesh term: Erlotinib Hydrochloride
mesh term: Dasatinib