<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/NCT01715142</url>
  </required_header>
  <id_info>
    <org_study_id>2012-003592-19</org_study_id>
    <nct_id>NCT01715142</nct_id>
  </id_info>
  <brief_title>Effect on Tumor Perfusion of a Chemotherapy Combining Gemcitabine and Nab-paclitaxel (Abraxane) in Pancreatic Cancer</brief_title>
  <acronym>NEOPAX-001</acronym>
  <official_title>Evaluation of Tumoral Perfusion Modification by Dynamic Imaging After Chemotherapy Combining Gemcitabine and Nab-paclitaxel (Abraxane) in Patients With Potentially Operable, Locally Advanced or Metastatic Pancreatic Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jean-Luc Van Laethem</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Erasme University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with conventional&#xD;
      treatments having little impact on disease course. Novel approaches are urgently needed to&#xD;
      address inherent resistance to the current therapies and to identify new drugs or&#xD;
      combinations that will have a high chance of success in pancreatic cancer patients. This&#xD;
      proof-of-concept trial is studying the &quot;dynamic&quot; tumor response after the administration of a&#xD;
      short course of gemcitabine and nab-paclitaxel (Abraxane) (a) during a window interval (4&#xD;
      weeks= 1 cycle) before surgery in resectable pancreatic cancer (cohort 1 = 21 patients) and&#xD;
      (b) during at least 8 weeks (2 cycles) in locally advanced or metastatic pancreatic cancer&#xD;
      (cohort 2 = 10 patients).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pancreatic cancer is a hypoperfused tumor, characterized by a high stroma density precluding&#xD;
      cytotoxics delivery to the epithelial tumoral compartment. There is thus a rationale for&#xD;
      combining chemotherapy and antistromal drugs like nab-paclitaxel (Abraxane), a solvent&#xD;
      (Cremophor® EL)-free, albumin-bound form of paclitaxel that has been initially developed to&#xD;
      reduce the toxicities associated with Taxol injection while maintaining or improving its&#xD;
      chemotherapeutic effect. This unique protein formulation provides a novel approach of&#xD;
      increasing intra-tumoral concentrations of the drug by a receptor-mediated transport process&#xD;
      allowing transcytosis across the endothelial cell.&#xD;
&#xD;
      Abraxane has been approved for commercialization in 38 countries, including the US, Canada,&#xD;
      the EU, Australia, China, India and Korea for the treatment of women with metastatic breast&#xD;
      cancer. Abraxane alone and in combination is being evaluated in a number of cancers,&#xD;
      including metastatic melanoma, non-small cell lung cancer, pancreatic cancer and other solid&#xD;
      tumors.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 21, 2013</start_date>
  <completion_date type="Actual">April 30, 2017</completion_date>
  <primary_completion_date type="Actual">September 21, 2015</primary_completion_date>
  <phase>Early 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>Dynamic tumor response rate as defined by a 40% modification of tumoral perfusion and cellular density parameters.</measure>
    <time_frame>4 weeks (duration of 1 cycle of neoadjuvant chemotherapy for resectable patients); 8 weeks (duration of 2 cycles of treatment for locally advanced and metastatic patients)</time_frame>
    <description>In order to detect changes in the tumor microenvironment and to monitor treatment efficacy, Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) and Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) constitute tools more and more used. The acquired data can be analyzed using a pharmacokinetic model to obtain quantitative parameters relative to tissue perfusion and vascular permeability (Ktrans, a volume transfer constant of contrast agent between blood plasma and the extravascular extracellular space; Apparent Coefficient Diffusion as a surrogate marker of tissue cellularity). DCE/DW-MRI will be achieved before each chemotherapy treatment (and also before surgery for resectable patients). Each patient will be his/her own control by comparing serial imaging results with those of the baseline MRI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0.</measure>
    <time_frame>12 months</time_frame>
    <description>Number of participants with (serious) adverse events will be considered as a measure of safety of the whole therapeutic sequence (gemcitabine+Abraxane+surgery for resectable patients; gemcitabine+Abraxane for locally advanced/metastatic patients)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria</measure>
    <time_frame>4 weeks (duration of 1 cycle of neoadjuvant chemotherapy for resectable patients); 8 weeks (duration of 2 cycles of treatment for locally advanced and metastatic patients)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Effect of treatment on selected biomarkers in tumor resection specimens (cohort 1) and in case of obtaining tissue by Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) (cohort 2)</measure>
    <time_frame>4 weeks (duration of 1 cycle of neoadjuvant chemotherapy for resectable patients); 8 weeks (duration of 2 cycles of treatment for locally advanced and metastatic patients)</time_frame>
    <description>Evaluation of biomarkers involved in gemcitabine and nab-paclitaxel activity : human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), cytidine deaminase (CDA), secreted protein acidic and rich in cysteine (SPARC), taxanes-related biomarkers.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Pancreatic Adenocarcinoma Resectable</condition>
  <condition>Pancreatic Adenocarcinoma Locally Advanced</condition>
  <condition>Pancreatic Adenocarcinoma Metastatic</condition>
  <arm_group>
    <arm_group_label>Gemcitabine+Abraxane</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Chemotherapy combining gemcitabine and Abraxane during 4 weeks (1 cycle) before surgery (cohort 1: resectable patients) and during at least 8 weeks (2 cycles or more in case of response of stable disease) (cohort 2: locally advanced and metastatic patients)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Administrated intravenously at a dose of 1000 mg/m2 over 30 minutes weekly, on day 1, day 8, day 15 followed by one week of rest (before surgery of before starting of the next cycle depending on the cohort allocation)</description>
    <arm_group_label>Gemcitabine+Abraxane</arm_group_label>
    <other_name>GEMZAR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abraxane</intervention_name>
    <description>Administrated intravenously at a dose of 125 mg/m2 over 30 minutes weekly, on day 1, day 8, day 15 followed by one week of rest (before surgery of before starting of the next cycle depending on the cohort allocation)</description>
    <arm_group_label>Gemcitabine+Abraxane</arm_group_label>
    <other_name>nab-paclitaxel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histo(cyto)logically proven ductal pancreatic adenocarcinoma;&#xD;
&#xD;
          -  Resectable or potentially resectable tumor; resectability assessed during a&#xD;
             multidisciplinary meeting with expert surgeon and radiologist (cohort 1), or locally&#xD;
             advanced and/or metastatic tumor (cohort 2);&#xD;
&#xD;
          -  First line chemotherapy;&#xD;
&#xD;
          -  Age &gt; 18 years;&#xD;
&#xD;
          -  WHO performance status (PS) grade 0 or 1;&#xD;
&#xD;
          -  Absolute neutrophil count &gt; 1.5 x 10 9 / L, platelets &gt; 100 x 10 9/ L, creatinine&#xD;
             clearance (Cockcroft and Gault formula) &gt; 60 ml/min, haemoglobin level &gt; 10 g/dl&#xD;
             (transfusions authorized), bilirubin&lt;1.5 g/dl;&#xD;
&#xD;
          -  Optimal biliary drainage;&#xD;
&#xD;
          -  Women of child-bearing potential (WCBP), defined as a sexually mature woman who has&#xD;
             not undergone a hysterectomy or tubal ligation of who has not been naturally&#xD;
             postmenopausal for at least 24 consecutive months, must have a negative serum or urine&#xD;
             pregnancy test prior to treatment. All WCBP, all sexually active male patients, and&#xD;
             all partners of patients must agree to use adequate methods of birth control&#xD;
             throughout the study;&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous anticancer therapy for the pancreatic adenocarcinoma;&#xD;
&#xD;
          -  Biliary obstruction without endoscopic biliary drainage;&#xD;
&#xD;
          -  Any contre-indication for surgery;&#xD;
&#xD;
          -  Prior malignancy (except non-melanoma skin cancer, and in situ carcinoma of the&#xD;
             uterine cervix treated with a curative intent and any other tumor in complete&#xD;
             remission with a disease-free interval &gt; 3 years);&#xD;
&#xD;
          -  Uncontrolled congestive heart failure or angina pectoris, myocardial infarction within&#xD;
             1 year prior to study entry, uncontrolled hypertension (systolic pressure &gt; 160 mm or&#xD;
             diastolic pressure &gt; 100 mm under well conducted antihypertensive treatment), QT&#xD;
             prolongation;&#xD;
&#xD;
          -  Major uncontrolled infection;&#xD;
&#xD;
          -  Severe hepatic impairment;&#xD;
&#xD;
          -  Any medical, psychological, or social condition, which, in the opinion of the&#xD;
             investigator, could hamper patient's compliance to the study protocol and/or&#xD;
             assessment/interpretation of the data;&#xD;
&#xD;
          -  Pregnant or lactating women, or patients of both genders with procreative potential&#xD;
             not using adequate contraceptive methods;&#xD;
&#xD;
          -  Patients receiving or having received any investigational treatment within 4 weeks&#xD;
             prior to study entry, or participating to another clinical study; patients previously&#xD;
             enrolled into this study.&#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>Jean-Luc Van Laethem, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Erasme University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Antwerp University Hospital (UZA)</name>
      <address>
        <city>Edegem</city>
        <state>Antwerpen</state>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasme University Hospital (ULB)</name>
      <address>
        <city>Brussels</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>October 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 26, 2012</study_first_posted>
  <last_update_submitted>September 2, 2020</last_update_submitted>
  <last_update_submitted_qc>September 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Erasme University Hospital</investigator_affiliation>
    <investigator_full_name>Jean-Luc Van Laethem</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Pancreatic cancer</keyword>
  <keyword>Nab-paclitaxel</keyword>
  <keyword>Gemcitabine</keyword>
  <keyword>Neoadjuvant chemotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</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>Albumin-Bound Paclitaxel</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/NCT01715142
org study id: 2012-003592-19
nct id: NCT01715142
lead sponsor: 
collaborator: 
has dmc: No
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with conventional
      treatments having little impact on disease course. Novel approaches are urgently needed to
      address inherent resistance to the current therapies and to identify new drugs or
      combinations that will have a high chance of success in pancreatic cancer patients. This
      proof-of-concept trial is studying the "dynamic" tumor response after the administration of a
      short course of gemcitabine and nab-paclitaxel (Abraxane) (a) during a window interval (4
      weeks= 1 cycle) before surgery in resectable pancreatic cancer (cohort 1 = 21 patients) and
      (b) during at least 8 weeks (2 cycles) in locally advanced or metastatic pancreatic cancer
      (cohort 2 = 10 patients).
Pancreatic cancer is a hypoperfused tumor, characterized by a high stroma density precluding
      cytotoxics delivery to the epithelial tumoral compartment. There is thus a rationale for
      combining chemotherapy and antistromal drugs like nab-paclitaxel (Abraxane), a solvent
      (Cremophor® EL)-free, albumin-bound form of paclitaxel that has been initially developed to
      reduce the toxicities associated with Taxol injection while maintaining or improving its
      chemotherapeutic effect. This unique protein formulation provides a novel approach of
      increasing intra-tumoral concentrations of the drug by a receptor-mediated transport process
      allowing transcytosis across the endothelial cell.

      Abraxane has been approved for commercialization in 38 countries, including the US, Canada,
      the EU, Australia, China, India and Korea for the treatment of women with metastatic breast
      cancer. Abraxane alone and in combination is being evaluated in a number of cancers,
      including metastatic melanoma, non-small cell lung cancer, pancreatic cancer and other solid
      tumors.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dynamic tumor response rate as defined by a 40% modification of tumoral perfusion and cellular density parameters.
time frame: 4 weeks (duration of 1 cycle of neoadjuvant chemotherapy for resectable patients); 8 weeks (duration of 2 cycles of treatment for locally advanced and metastatic patients)
description: In order to detect changes in the tumor microenvironment and to monitor treatment efficacy, Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) and Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) constitute tools more and more used. The acquired data can be analyzed using a pharmacokinetic model to obtain quantitative parameters relative to tissue perfusion and vascular permeability (Ktrans, a volume transfer constant of contrast agent between blood plasma and the extravascular extracellular space; Apparent Coefficient Diffusion as a surrogate marker of tissue cellularity). DCE/DW-MRI will be achieved before each chemotherapy treatment (and also before surgery for resectable patients). Each patient will be his/her own control by comparing serial imaging results with those of the baseline MRI.
measure: Number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0.
time frame: 12 months
description: Number of participants with (serious) adverse events will be considered as a measure of safety of the whole therapeutic sequence (gemcitabine+Abraxane+surgery for resectable patients; gemcitabine+Abraxane for locally advanced/metastatic patients)
measure: Tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
time frame: 4 weeks (duration of 1 cycle of neoadjuvant chemotherapy for resectable patients); 8 weeks (duration of 2 cycles of treatment for locally advanced and metastatic patients)
measure: Effect of treatment on selected biomarkers in tumor resection specimens (cohort 1) and in case of obtaining tissue by Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) (cohort 2)
time frame: 4 weeks (duration of 1 cycle of neoadjuvant chemotherapy for resectable patients); 8 weeks (duration of 2 cycles of treatment for locally advanced and metastatic patients)
description: Evaluation of biomarkers involved in gemcitabine and nab-paclitaxel activity : human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), cytidine deaminase (CDA), secreted protein acidic and rich in cysteine (SPARC), taxanes-related biomarkers.
arm group label: Gemcitabine+Abraxane
arm group type: Experimental
description: Chemotherapy combining gemcitabine and Abraxane during 4 weeks (1 cycle) before surgery (cohort 1: resectable patients) and during at least 8 weeks (2 cycles or more in case of response of stable disease) (cohort 2: locally advanced and metastatic patients)
intervention type: Drug
intervention name: Gemcitabine
description: Administrated intravenously at a dose of 1000 mg/m2 over 30 minutes weekly, on day 1, day 8, day 15 followed by one week of rest (before surgery of before starting of the next cycle depending on the cohort allocation)
arm group label: Gemcitabine+Abraxane
other name: GEMZAR
intervention type: Drug
intervention name: Abraxane
description: Administrated intravenously at a dose of 125 mg/m2 over 30 minutes weekly, on day 1, day 8, day 15 followed by one week of rest (before surgery of before starting of the next cycle depending on the cohort allocation)
arm group label: Gemcitabine+Abraxane
other name: nab-paclitaxel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean-Luc Van Laethem, MD, PhD
role: Principal Investigator
affiliation: Erasme University Hospital
facility: 
facility: 
country: Belgium
responsible party type: Sponsor-Investigator
investigator affiliation: Erasme University Hospital
investigator full name: Jean-Luc Van Laethem
investigator title: MD, PhD
mesh term: Adenocarcinoma
mesh term: Paclitaxel
mesh term: Gemcitabine
mesh term: Albumin-Bound Paclitaxel