<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/NCT02207465</url>
  </required_header>
  <id_info>
    <org_study_id>UPCC 32213</org_study_id>
    <nct_id>NCT02207465</nct_id>
  </id_info>
  <brief_title>A Phase I Dual Dose Escalation Study of Radiation and Nab-Paclitaxel in Patients With Unresectable and Borderline Resectable Pancreatic Cancer</brief_title>
  <official_title>A Phase I Dual Dose Escalation Study of Radiation and Nab-Paclitaxel in Patients With Unresectable and Borderline Resectable Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Abramson Cancer Center at Penn Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Abramson Cancer Center at Penn Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesize that intensification of local therapy will lead to improvements&#xD;
      in local control and survival in patients with unresectable and borderline resectable&#xD;
      pancreatic cancer. We propose to do this by combining nab-paclitaxel concurrently with&#xD;
      dose-escalated radiation therapy. In the first part of this phase I study (sub-trial 1), the&#xD;
      nab-paclitaxel dose will be escalated while the radiation dose is held constant at a&#xD;
      standardly accepted level. The use of this novel chemoradiotherapy regimen will take&#xD;
      advantage of nab-paclitaxel's specific anti-tumor and anti-stromal properties, which may&#xD;
      enhance the efficacy of radiation therapy, and thereby improve local control. After the MTD&#xD;
      of nab-paclitaxel had been determined, a second arm in sub-trial 1 will evaluate the addition&#xD;
      of paricalcitol to nab-paclitaxel concurrently with dose-escalated radiation therapy. In&#xD;
      addition, after the MTD of the nab-paclitaxel is reached in sub-trial 1 arm A, in the second&#xD;
      part of this study (sub-trial 2), we will administer nab-paclitaxel at the determined MTD&#xD;
      concurrently with escalated doses of radiation. We will utilize IMRT or protons to safely&#xD;
      deliver high doses of radiation while maximally sparing surrounding normal tissue. Patients&#xD;
      will also preferentially have 2-3 fiducial markers placed in or around the tumor for daily&#xD;
      localization. Chemotherapy before and/or after chemoradiotherapy may be given as per standard&#xD;
      of care. Correlative tissue and serum biomarkers are an important, but optional, part of this&#xD;
      study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2025</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>Number of Adverse Events</measure>
    <time_frame>4 years</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">42</enrollment>
  <condition>Locally Advanced Unresectable Pancreatic Cancer Treated With Chemoradiotherapy</condition>
  <condition>Borderline Resectable Pancreatic Cancer Treated With Chemoradiotherapy</condition>
  <arm_group>
    <arm_group_label>Subtrial 1-Arm A (Dose Level 1 of Abraxane)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Determine if it is safe or not (via occurrence of dose limiting toxicities) for patients to receive both Abraxane and radiation therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Subtrial 1-Arm B (Dose Level 2 of Abraxane: 3+4 enrollment)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Determine the maximum dose of Abraxane that is allowable and safe for patients receiving both Abraxane and radiation therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Subtrial 2- Abraxane 125mg; Borderline get 55cGY, unresectable get 57.5cGY until next escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiotherapy</intervention_name>
    <arm_group_label>Subtrial 1-Arm A (Dose Level 1 of Abraxane)</arm_group_label>
    <arm_group_label>Subtrial 1-Arm B (Dose Level 2 of Abraxane: 3+4 enrollment)</arm_group_label>
    <arm_group_label>Subtrial 2- Abraxane 125mg; Borderline get 55cGY, unresectable get 57.5cGY until next escalation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abraxane</intervention_name>
    <description>Dose varies within subtrial 1 to determine maximum dose. All patients in subtrial 2 receive 125mg Abraxane</description>
    <arm_group_label>Subtrial 1-Arm A (Dose Level 1 of Abraxane)</arm_group_label>
    <arm_group_label>Subtrial 1-Arm B (Dose Level 2 of Abraxane: 3+4 enrollment)</arm_group_label>
    <arm_group_label>Subtrial 2- Abraxane 125mg; Borderline get 55cGY, unresectable get 57.5cGY until next escalation</arm_group_label>
    <other_name>nab-paclitaxel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically confirmed adenocarcinoma of the pancreas.&#xD;
&#xD;
          -  Unresectable disease or borderline resectable disease assessed by a multidisciplinary&#xD;
             panel of pancreas surgeon, medical and radiation oncologist, and a radiologist.&#xD;
             Criteria defining unresectable and borderline resectable patients will be based on the&#xD;
             NCCN Guidelines (v 1.2014):&#xD;
&#xD;
        Unresectable&#xD;
&#xD;
          -  Greater than 180 degrees of SMA encasement&#xD;
&#xD;
          -  Any celiac abutment&#xD;
&#xD;
          -  Unreconstructible SMV/portal occlusion&#xD;
&#xD;
          -  Aortic invasion or encasement&#xD;
&#xD;
          -  Nodal metastases beyond the field of resection Borderline resectable&#xD;
&#xD;
          -  Venous involvement of the SMV/portal vein demonstrating tumor abutment with&#xD;
             impingement and narrowing of the lumen&#xD;
&#xD;
          -  Encasement of the SMV/portal vein but without encasement of the nearby arteries&#xD;
&#xD;
          -  Short-segment venous occlusion resulting from either tumor thrombus or encasement with&#xD;
             suitable proximal and distal vessel for reconstruction/grafting.&#xD;
&#xD;
          -  Gastroduodenal artery encasement up to the hepatic artery with either short segment&#xD;
             encasement or direct abutment of the hepatic artery, without extension to celiac axis&#xD;
&#xD;
          -  Tumor abutment to SMA but not to exceed greater than 180 degrees of circumferential&#xD;
             vessel wall&#xD;
&#xD;
          -  Age &gt; 18 years.&#xD;
&#xD;
          -  ECOG performance status of ≤ 1.&#xD;
&#xD;
          -  Adequate organ function defined as follows: absolute neutrophil count of ≥ 1500/mm3,&#xD;
             platelets ≥ 100,000/mm3, serum creatinine ≤ 2 mg/dl, total bilirubin ≤ 3, (with relief&#xD;
             of biliary obstruction if present (PTC tube or endobiliary stent) and AST &lt; 5 times&#xD;
             the upper limit of normal.&#xD;
&#xD;
          -  Patients of reproductive potential must agree to use an effective contraceptive method&#xD;
             during participation in this trial and for 6 months after the trial.&#xD;
&#xD;
          -  Patients must be able to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Distant metastatic disease.&#xD;
&#xD;
          -  Prior history of abdominal radiation therapy.&#xD;
&#xD;
          -  Prior systemic therapy for pancreatic cancer.&#xD;
&#xD;
          -  Prior or simultaneous malignancy within the past 2 years (other than cutaneous&#xD;
             squamous or basal cell carcinoma, melanoma in situ, thyroid carcinoma, or low-risk&#xD;
             prostate cancer). In-situ carcinoma is allowed.&#xD;
&#xD;
          -  Serious uncontrolled concomitant systemic disorders or psychiatric condition that&#xD;
             would interfere with the safe delivery of protocol therapy.&#xD;
&#xD;
          -  Treatment with an investigational anti-cancer agent within 4 weeks prior to enrollment&#xD;
             into the study.&#xD;
&#xD;
          -  Pregnant women, women planning to become pregnant and women that are nursing&#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>Edgar Ben-Josef, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Abramson Cancer Center at Penn Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Edgar Ben-Josef, MD</last_name>
    <phone>855-216-0098</phone>
    <email>PennCancerTrials@emergingmed.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Abramson Cancer Center of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dana Patsch</last_name>
      <phone>215-615-5645</phone>
      <email>Dana.Patsch@uphs.upenn.edu</email>
    </contact>
    <investigator>
      <last_name>Edgar Ben-Josef, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>August 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <last_update_submitted>January 9, 2023</last_update_submitted>
  <last_update_submitted_qc>January 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 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>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>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/NCT02207465
org study id: UPCC 32213
nct id: NCT02207465
lead sponsor: 
has dmc: Yes
The investigators hypothesize that intensification of local therapy will lead to improvements
      in local control and survival in patients with unresectable and borderline resectable
      pancreatic cancer. We propose to do this by combining nab-paclitaxel concurrently with
      dose-escalated radiation therapy. In the first part of this phase I study (sub-trial 1), the
      nab-paclitaxel dose will be escalated while the radiation dose is held constant at a
      standardly accepted level. The use of this novel chemoradiotherapy regimen will take
      advantage of nab-paclitaxel's specific anti-tumor and anti-stromal properties, which may
      enhance the efficacy of radiation therapy, and thereby improve local control. After the MTD
      of nab-paclitaxel had been determined, a second arm in sub-trial 1 will evaluate the addition
      of paricalcitol to nab-paclitaxel concurrently with dose-escalated radiation therapy. In
      addition, after the MTD of the nab-paclitaxel is reached in sub-trial 1 arm A, in the second
      part of this study (sub-trial 2), we will administer nab-paclitaxel at the determined MTD
      concurrently with escalated doses of radiation. We will utilize IMRT or protons to safely
      deliver high doses of radiation while maximally sparing surrounding normal tissue. Patients
      will also preferentially have 2-3 fiducial markers placed in or around the tumor for daily
      localization. Chemotherapy before and/or after chemoradiotherapy may be given as per standard
      of care. Correlative tissue and serum biomarkers are an important, but optional, part of this
      study.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Adverse Events
time frame: 4 years
arm group label: Subtrial 1-Arm A (Dose Level 1 of Abraxane)
arm group type: Experimental
description: Determine if it is safe or not (via occurrence of dose limiting toxicities) for patients to receive both Abraxane and radiation therapy.
arm group label: Subtrial 1-Arm B (Dose Level 2 of Abraxane: 3+4 enrollment)
arm group type: Experimental
description: Determine the maximum dose of Abraxane that is allowable and safe for patients receiving both Abraxane and radiation therapy.
arm group label: Subtrial 2- Abraxane 125mg; Borderline get 55cGY, unresectable get 57.5cGY until next escalation
arm group type: Experimental
intervention type: Radiation
intervention name: Radiotherapy
arm group label: Subtrial 1-Arm A (Dose Level 1 of Abraxane)
arm group label: Subtrial 1-Arm B (Dose Level 2 of Abraxane: 3+4 enrollment)
arm group label: Subtrial 2- Abraxane 125mg; Borderline get 55cGY, unresectable get 57.5cGY until next escalation
intervention type: Drug
intervention name: Abraxane
description: Dose varies within subtrial 1 to determine maximum dose. All patients in subtrial 2 receive 125mg Abraxane
arm group label: Subtrial 1-Arm A (Dose Level 1 of Abraxane)
arm group label: Subtrial 1-Arm B (Dose Level 2 of Abraxane: 3+4 enrollment)
arm group label: Subtrial 2- Abraxane 125mg; Borderline get 55cGY, unresectable get 57.5cGY until next escalation
other name: nab-paclitaxel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Edgar Ben-Josef, MD
role: Principal Investigator
affiliation: Abramson Cancer Center at Penn Medicine
last name: Edgar Ben-Josef, MD
phone: 855-216-0098
email: PennCancerTrials@emergingmed.com
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel