<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/NCT01688791</url>
  </required_header>
  <id_info>
    <org_study_id>8109-001</org_study_id>
    <secondary_id>2012-002799-14</secondary_id>
    <nct_id>NCT01688791</nct_id>
  </id_info>
  <brief_title>A Study of MK-8109 (Vintafolide) Given Alone or With Chemotherapy in Participants With Advanced Cancers (MK-8109-001)</brief_title>
  <official_title>A Phase I Dose Escalation Study Evaluating Vintafolide (MK-8109) Chemotherapy Alone or in Combination in Adult Subjects With Advanced Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Endocyte</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Endocyte</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial will be conducted in three parts. Part A is a dose escalation trial followed by a&#xD;
      dose confirmation trial in folate receptor (FR) 100% endometrial cancer participants. The&#xD;
      primary hypothesis of this trial is that administration of vintafolide in combination with&#xD;
      carboplatin and paclitaxel is safe and tolerable. Part B is a single dose, dose escalation,&#xD;
      pharmacokinetic (PK), and QTc interval trial. The primary objectives include determination of&#xD;
      the maximum single tolerated dose of vintafolide and to evaluate the effect of this single&#xD;
      maximum dose on the QTc interval. Part C is a weekly dose escalation trial of vintafolide&#xD;
      followed by a dose confirmation. The primary hypothesis of this part is that weekly&#xD;
      vintafolide has acceptable safety and tolerability in participants with advanced cancers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Parts A and C: Number of participants with dose-limiting toxicities (DLTs)</measure>
    <time_frame>Cycle 1 (21 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Change from Baseline in QTc interval</measure>
    <time_frame>30 minutes pre-dose and up to 2 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: Number of Participants Experiencing an Adverse Event (AE)</measure>
    <time_frame>Up to 18 weeks (six 3-week cycles)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants whose best response is partial response (PR) or complete response (CR)</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Pharmacokinetics (PK) of vintafolide, including Area Under the Curve (AUC) and Maximum Concentration (Cmax)</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: PK of Vintafolide Metabolites, including AUC and Cmax</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Advanced Cancer</condition>
  <arm_group>
    <arm_group_label>Part A: Vintafolide BIW</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vintafolide, intravenously (IV), on Days 1, 4, 8, and 11 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m^2, administered on Day 1 of each 21-day cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: Vintafolide TIW</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vintafolide, intravenously (IV) on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m^2, administered on Day 1 of each 21-day cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parts B &amp; C: Vintafolide Single Dose &amp; Weekly (QW)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose, dose escalation, vintafolide (Part B) followed by 2 week observation. Those completing Part B will have the option to continue on to Part C (weekly dosing, dose finding, on Days 1, 8, and 15 in a 21-day cycle until disease progression or toxicity) unless they experience severe and/or persistent drug related toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vintafolide</intervention_name>
    <arm_group_label>Part A: Vintafolide BIW</arm_group_label>
    <arm_group_label>Part A: Vintafolide TIW</arm_group_label>
    <arm_group_label>Parts B &amp; C: Vintafolide Single Dose &amp; Weekly (QW)</arm_group_label>
    <other_name>MK-8109</other_name>
    <other_name>EC-145</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <arm_group_label>Part A: Vintafolide BIW</arm_group_label>
    <arm_group_label>Part A: Vintafolide TIW</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <arm_group_label>Part A: Vintafolide BIW</arm_group_label>
    <arm_group_label>Part A: Vintafolide TIW</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria for all participants:&#xD;
&#xD;
          -  Histologically-confirmed metastatic or locally advanced solid tumor that has failed to&#xD;
             respond to standard therapy, progressed despite standard therapy, or for which&#xD;
             standard therapy does not exist or is unacceptable to the participant&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  At least one measurable metastatic or recurrent lesion&#xD;
&#xD;
          -  No history of a previous malignancy with the exception of cervical intraepithelial&#xD;
             neoplasia, basal cell carcinoma of the skin, or adequately treated localized prostate&#xD;
             carcinoma; or has undergone potentially curative therapy with no evidence of disease&#xD;
             for five years&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
          -  Female participants of childbearing potential must be willing to use acceptable&#xD;
             methods of birth control or abstain from heterosexual activity for the course of the&#xD;
             study through 90 days after the last dose of study therapy&#xD;
&#xD;
          -  Male participants must agree to use an adequate method of contraception for&#xD;
             heterosexual activity starting with the first dose of study therapy through 90 days&#xD;
             after the last dose of study therapy&#xD;
&#xD;
        Inclusion criteria for Part A:&#xD;
&#xD;
          -  Tumor lesions characterized as folate receptor (FR) 100% as determined by an&#xD;
             etarfolide Sequential Single Photon Emission Computed Tomography (SPECT) and CT scan&#xD;
&#xD;
          -  Histologically-confirmed diagnosis of locally advanced or metastatic or recurrent&#xD;
             endometrial cancer&#xD;
&#xD;
        Inclusion criteria for Parts B &amp; C:&#xD;
&#xD;
        - Must have an etarfolatide SPECT/CT scan to determine FR status&#xD;
&#xD;
        Exclusion criteria for all participants:&#xD;
&#xD;
          -  Part A &amp; Part C if enrolled after completion of Part B: Chemotherapy, radiotherapy, or&#xD;
             biological therapy (including monoclonal antibodies) within 4 weeks prior to drug&#xD;
             administration, or not recovered from adverse events due to agents administered more&#xD;
             than 4 weeks earlier&#xD;
&#xD;
          -  Part B: Chemotherapy, radiotherapy, or biological therapy (including monoclonal&#xD;
             antibodies) within 3 weeks prior to drug administration, or not recovered from adverse&#xD;
             events due to agents administered more than 4 weeks earlier&#xD;
&#xD;
          -  Currently participating or has participated in a study with an investigational&#xD;
             compound or device within 28 days of initial dosing on this study&#xD;
&#xD;
          -  Part A, dose escalation, Parts B and C: More than 3 prior cytotoxic regimens for&#xD;
             metastatic disease.&#xD;
&#xD;
          -  Part A, dose confirmation: Has received more than 2 prior cytotoxic regimens for&#xD;
             metastatic disease.&#xD;
&#xD;
          -  Primary central nervous system (CNS) tumor&#xD;
&#xD;
          -  Active CNS metastases and/or carcinomatous meningitis.&#xD;
&#xD;
          -  Known hypersensitivity to the components of the study therapy or its analogs&#xD;
&#xD;
          -  Recent (i.e., ≤ 6 weeks) history of abdominal surgery or peritonitis&#xD;
&#xD;
          -  Bowel occlusion or sub-occlusion&#xD;
&#xD;
          -  Prior whole abdominal or whole pelvis radiation therapy or radiation therapy to &gt;10%&#xD;
             of the bone marrow at any time in the past or prior radiation therapy within the last&#xD;
             3 years to the breast / sternum, head, or neck&#xD;
&#xD;
          -  Requires anti-folate therapy for the management of co-morbid conditions&#xD;
&#xD;
          -  Known regular user (including &quot;recreational use&quot;) of any illicit drugs or had a recent&#xD;
             history (within the last year) of drug or alcohol abuse&#xD;
&#xD;
          -  Pregnant or breastfeeding or expecting to conceive, or donate sperm within the span of&#xD;
             the study&#xD;
&#xD;
          -  Human Immunodeficiency Virus (HIV)-positive&#xD;
&#xD;
          -  Active Hepatitis B or C&#xD;
&#xD;
          -  Symptomatic ascites or pleural effusion.&#xD;
&#xD;
          -  History of stem cell or bone marrow transplant&#xD;
&#xD;
        Exclusion Criteria for Part B:&#xD;
&#xD;
          -  Permanent pacemaker&#xD;
&#xD;
          -  Unable to refrain from use of all concomitant medications on Day 1&#xD;
&#xD;
          -  Structural heart disease, history of myocardial infarction (MI), or unstable angina&#xD;
&#xD;
          -  History of cardiac arrhythmia, congestive heart failure (CHF), sick sinus syndrome,&#xD;
             second or third degree atrioventricular (AV) block&#xD;
&#xD;
          -  History of risk factors for Torsades de Pointes such as CHF, uncorrected hypokalemia,&#xD;
             family history of long QT syndrome&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <removed_countries>
    <country>France</country>
    <country>Israel</country>
    <country>United States</country>
  </removed_countries>
  <verification_date>February 2015</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 20, 2012</study_first_posted>
  <last_update_submitted>February 9, 2015</last_update_submitted>
  <last_update_submitted_qc>February 9, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 10, 2015</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>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>Carboplatin</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/NCT01688791
org study id: 8109-001
secondary id: 2012-002799-14
nct id: NCT01688791
lead sponsor: 
has dmc: No
This trial will be conducted in three parts. Part A is a dose escalation trial followed by a
      dose confirmation trial in folate receptor (FR) 100% endometrial cancer participants. The
      primary hypothesis of this trial is that administration of vintafolide in combination with
      carboplatin and paclitaxel is safe and tolerable. Part B is a single dose, dose escalation,
      pharmacokinetic (PK), and QTc interval trial. The primary objectives include determination of
      the maximum single tolerated dose of vintafolide and to evaluate the effect of this single
      maximum dose on the QTc interval. Part C is a weekly dose escalation trial of vintafolide
      followed by a dose confirmation. The primary hypothesis of this part is that weekly
      vintafolide has acceptable safety and tolerability in participants with advanced cancers.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Parts A and C: Number of participants with dose-limiting toxicities (DLTs)
time frame: Cycle 1 (21 days)
measure: Part B: Change from Baseline in QTc interval
time frame: 30 minutes pre-dose and up to 2 hours post-dose
measure: Part C: Number of Participants Experiencing an Adverse Event (AE)
time frame: Up to 18 weeks (six 3-week cycles)
measure: Number of participants whose best response is partial response (PR) or complete response (CR)
time frame: Week 6
measure: Progression free survival
time frame: Week 6
measure: Disease control rate
time frame: Week 6
measure: Part B: Pharmacokinetics (PK) of vintafolide, including Area Under the Curve (AUC) and Maximum Concentration (Cmax)
time frame: Day 1
measure: Part B: PK of Vintafolide Metabolites, including AUC and Cmax
time frame: Day 1
arm group label: Part A: Vintafolide BIW
arm group type: Experimental
description: Vintafolide, intravenously (IV), on Days 1, 4, 8, and 11 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m^2, administered on Day 1 of each 21-day cycle
arm group label: Part A: Vintafolide TIW
arm group type: Experimental
description: Vintafolide, intravenously (IV) on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m^2, administered on Day 1 of each 21-day cycle
arm group label: Parts B & C: Vintafolide Single Dose & Weekly (QW)
arm group type: Experimental
description: Single dose, dose escalation, vintafolide (Part B) followed by 2 week observation. Those completing Part B will have the option to continue on to Part C (weekly dosing, dose finding, on Days 1, 8, and 15 in a 21-day cycle until disease progression or toxicity) unless they experience severe and/or persistent drug related toxicity.
intervention type: Drug
intervention name: Vintafolide
arm group label: Part A: Vintafolide BIW
arm group label: Part A: Vintafolide TIW
arm group label: Parts B & C: Vintafolide Single Dose & Weekly (QW)
other name: MK-8109
other name: EC-145
intervention type: Drug
intervention name: Carboplatin
arm group label: Part A: Vintafolide BIW
arm group label: Part A: Vintafolide TIW
intervention type: Drug
intervention name: Paclitaxel
arm group label: Part A: Vintafolide BIW
arm group label: Part A: Vintafolide TIW
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
country: France
country: Israel
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Paclitaxel
mesh term: Carboplatin