<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/NCT04484909</url>
  </required_header>
  <id_info>
    <org_study_id>2019-1001</org_study_id>
    <secondary_id>NCI-2020-03731</secondary_id>
    <secondary_id>2019-1001</secondary_id>
    <nct_id>NCT04484909</nct_id>
  </id_info>
  <brief_title>NBTXR3 Activated by Radiation Therapy for the Treatment of Locally Advanced or Borderline-Resectable Pancreatic Cancer</brief_title>
  <official_title>Phase I Study of NBTXR3 Activated by Radiotherapy for Locally Advanced or Borderline Resectable Pancreatic Ductal Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</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>
      To find the recommended dose of NBTXR3 that can be given in combination with radiation&#xD;
      therapy to patients with pancreatic cancer. To learn if the dose NBTXR3 found in Part 1 can&#xD;
      help to control the disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      • To determine the recommended phase II dose (RP2D) of NBTXR3 activated by radiotherapy in&#xD;
      subjects with locally advanced or borderline-resectable pancreatic ductal adenocarcinoma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
        -  To evaluate the safety and feasibility of NBTXR3 intratumoral injection activated by&#xD;
           radiotherapy in locally advanced or borderline-resectable pancreatic ductal&#xD;
           adenocarcinoma&#xD;
&#xD;
        -  To evaluate the anti-tumor response of NBTXR3 intratumoral injection activated by&#xD;
           radiotherapy in subjects with locally advanced or borderline-resectable pancreatic&#xD;
           ductal adenocarcinoma&#xD;
&#xD;
        -  To evaluate time-to-event outcomes in subjects with locally advanced or&#xD;
           borderline-resectable pancreatic ductal adenocarcinoma&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
        -  To evaluate the body kinetic profile of intratumorally injected NBTXR3.&#xD;
&#xD;
        -  To evaluate time to event outcomes for subjects with clinical staging of locally&#xD;
           advanced, unresectable disease.&#xD;
&#xD;
        -  To evaluate resectability conversion rates.&#xD;
&#xD;
        -  To evaluate surgical outcomes in subjects who undergo surgery after radiation therapy.&#xD;
&#xD;
        -  To associate radiomic measurements with outcomes.&#xD;
&#xD;
        -  To evaluate biomarkers of response in subjects treated with NBTXR3/RT.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of NBTXR3.&#xD;
&#xD;
      Patients receive NBTXR3 intratumorally (IT) on day 1. Patients then undergo 15 fractions of&#xD;
      intensity modulated radiation therapy (IMRT) between days 15-43 in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 1 month and then every 3&#xD;
      months for up to 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2026</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2026</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <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>Dose-limiting toxicities</measure>
    <time_frame>4 weeks after last radiation dose</time_frame>
    <description>Any grade &gt;= 3 adverse event related to NBTXR3 and/or radiation therapy. Any toxicity (grade &gt;= 3) that is at least possibly related to study drug (NBTXR3) is a DLT. Adverse events will be scored based on National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD)</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>MTD will be determined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate 30%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended phase II dose (RP2D)</measure>
    <time_frame>Up to 1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determination of the feasibility of NBTXR3 injection in pancreas</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Feasibility refers to the ability to do intratumoral injection of NBTXR3. The outcome for each patient would be &quot;feasible&quot; or &quot;not feasible.&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>From NBTXR3 injection to local recurrence, local progression, distant progression, or death from any cause, whichever occurs first, assessed up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From NBTXR3 injection to death from any cause or EoS, whichever occurs first, assessed up to 1 year</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Presence of hafnium</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will evaluation of the time-course dependent presence of hafnium in blood and urine following NBTXR3 intratumoral injection.</description>
  </other_outcome>
  <other_outcome>
    <measure>Disease control rate</measure>
    <time_frame>6 months</time_frame>
    <description>Defined as the proportion of patients without progression 6 months post NBTXR3 injection.</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of locally advanced subjects who undergo surgical resection after receiving NBTXR3/radiation therapy (R3/RT)</measure>
    <time_frame>Up to 1 year</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Resection status</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Resection status as assessed macroscopically by surgeon R0- Macroscopically complete tumor removal with negative microscopic surgical margins, R1- Macroscopically complete tumor removal with positive microscopic margins (any or all), and R2- Macroscopically incomplete tumor removal with known or suspected residual gross disease.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Borderline Resectable Pancreatic Adenocarcinoma</condition>
  <condition>Locally Advanced Pancreatic Ductal Adenocarcinoma</condition>
  <condition>Resectable Pancreatic Ductal Adenocarcinoma</condition>
  <condition>Stage III Pancreatic Cancer AJCC v8</condition>
  <arm_group>
    <arm_group_label>Treatment (NBTXR3, radiation therapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive NBTXR3 IT on day 1. Patients then undergo 15 fractions of radiation therapy between days 15-43 in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Hafnium Oxide-containing Nanoparticles NBTXR3</intervention_name>
    <description>Given IT</description>
    <arm_group_label>Treatment (NBTXR3, radiation therapy)</arm_group_label>
    <other_name>NBTXR3</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>Undergo radiation therapy</description>
    <arm_group_label>Treatment (NBTXR3, radiation therapy)</arm_group_label>
    <other_name>Cancer Radiotherapy</other_name>
    <other_name>Irradiate</other_name>
    <other_name>Irradiated</other_name>
    <other_name>Irradiation</other_name>
    <other_name>Radiation</other_name>
    <other_name>Radiation Therapy, NOS</other_name>
    <other_name>Radiotherapeutics</other_name>
    <other_name>Radiotherapy</other_name>
    <other_name>RT</other_name>
    <other_name>Therapy, Radiation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1. Signed informed consent form (ICF) indicating that participant understands the purpose&#xD;
        of, and procedures required for, the study and is willing to participate in the study 2.&#xD;
        Age ≥ 18 years 3. Biopsy proven ductal adenocarcinoma of the pancreas,as defined by the&#xD;
        following:&#xD;
&#xD;
        a. Borderline resectable pancreatic adenocarcinoma (BRPC) has no aortic involvement with at&#xD;
        least ONE of the following features: i. Superior mesenteric vein (SMV) or Portal vein (PV)&#xD;
        with a tumor interface of ≥ 180° OR short segment occlusion of SMV or PV amenable to&#xD;
        reconstruction ii. Superior mesenteric artery (SMA) or celiac axis (CA) with a tumor&#xD;
        interface of &lt; 180° iii. Any degree of hepatic artery interface that is amenable to&#xD;
        reconstruction b. Locally advanced pancreatic adenocarcinoma (LAPC) has at least ONE of the&#xD;
        following features:&#xD;
&#xD;
          1. Signed informed consent form (ICF) indicating that participant understands the purpose&#xD;
             of, and procedures required for, the study and is willing to participate in the study&#xD;
&#xD;
          2. Age ≥ 18 years&#xD;
&#xD;
          3. Biopsy proven ductal adenocarcinoma of the pancreas,as defined by the following:&#xD;
&#xD;
             a. Borderline resectable pancreatic adenocarcinoma (BRPC) has no aortic involvement&#xD;
             with at least ONE of the following features: i. Superior mesenteric vein (SMV) or&#xD;
             Portal vein (PV) with a tumor interface of ≥ 180° OR short segment occlusion of SMV or&#xD;
             PV amenable to reconstruction ii. Superior mesenteric artery (SMA) or celiac axis (CA)&#xD;
             with a tumor interface of &lt; 180° iii. Any degree of hepatic artery interface that is&#xD;
             amenable to reconstruction b. Locally advanced pancreatic adenocarcinoma (LAPC) has at&#xD;
             least ONE of the following features: i. Occlusion of the SMV or PV that is not&#xD;
             amenable to reconstruction ii. Tumor interface of the superior mesenteric artery or&#xD;
             celiac axis ≥ 180° iii. Involvement of the hepatic artery that is not amenable to&#xD;
             reconstruction iv. Involvement of the aorta&#xD;
&#xD;
          4. Has had a 4-month course (± 2-months) of chemotherapy for PDAC without radiographic&#xD;
             evidence of distant metastatic disease. Following chemotherapy regimens are allowed:&#xD;
&#xD;
               1. gemcitabine/nab-paclitaxel&#xD;
&#xD;
               2. gemcitabine/capecitabine&#xD;
&#xD;
               3. gemcitabine/cisplatin&#xD;
&#xD;
               4. gemcitabine&#xD;
&#xD;
               5. FOLFOX&#xD;
&#xD;
               6. FOLFIRINOX&#xD;
&#xD;
          5. Amenable to undergo the endoscopic ultrasound guided injection of NBTXR3 as per&#xD;
             investigator or treating physician.&#xD;
&#xD;
          6. Has a target lesion in the pancreas that is identifiable on cross sectional imaging by&#xD;
             repeated measurements (via RECIST 1.1) at the same anatomical location&#xD;
&#xD;
             a. Nodal disease only is not allowed.&#xD;
&#xD;
          7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1&#xD;
&#xD;
          8. Laboratory Values at screening:&#xD;
&#xD;
               1. Hemoglobin ≥ 8.0 g/dL&#xD;
&#xD;
               2. Absolute Neutrophil Count (ANC) ≥ 1,500/mm3&#xD;
&#xD;
               3. Platelet Count ≥ 100,000/mm3&#xD;
&#xD;
               4. Creatinine ≤ 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
               5. Total Bilirubin ≤ 2.0 mg/dL&#xD;
&#xD;
               6. AST / ALT ≤ 3.0 x upper limit of normal (ULN)&#xD;
&#xD;
               7. Serum albumin ≥ 3.0 g/dL&#xD;
&#xD;
          9. Negative pregnancy test ≤ 7 days prior to NBTXR3 injection in all females of&#xD;
             child-bearing potential&#xD;
&#xD;
         10. If participant has a history of prior duodenal or biliar plastic stent, it should be&#xD;
             replaced with a metal stent ≥ 1 week prior to Study Day 1.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior radiation therapy to the upper abdomen&#xD;
&#xD;
          2. Prior surgical resection of pancreatic tumor&#xD;
&#xD;
          3. Diagnosis other than pancreatic ductal adenocarcinoma. All other histologic types&#xD;
             (i.e., adenosquamous, cystadenocarcinoma, etc.) are not eligible to participate on&#xD;
             this study.&#xD;
&#xD;
          4. LAPC or BRPC with radiographic evidence of distant metastasis at screening.&#xD;
&#xD;
          5. Has received any approved or investigational anti-neoplastic agent other than the&#xD;
             chemotherapies specified in this protocol (i.e. chemotherapies included in Inclusion&#xD;
             #4)&#xD;
&#xD;
          6. Known uncontrolled (Grade ≥ 2) or active gastric or duodenal ulcer disease within 30&#xD;
             days of enrollment&#xD;
&#xD;
          7. Known contraindication to iodine-based or gadolinium-based IV contrast&#xD;
&#xD;
          8. Active malignancy, in addition to pancreatic cancer, with the exception of basal cell&#xD;
             carcinoma of the skin definitively treated and relapse free within at least 1 year&#xD;
             from diagnosis&#xD;
&#xD;
          9. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular&#xD;
             fibrillation, torsades de pointes, second or third degree atrioventricular heart block&#xD;
             without a permanent pacemaker in place)&#xD;
&#xD;
         10. Class III or IV Congestive Heart Failure as defined by the New York Heart Association&#xD;
             functional classification system &lt;6 months prior to screening&#xD;
&#xD;
         11. Known active, uncontrolled (high viral load) HIV or hepatitis B or hepatitis C&#xD;
             infection&#xD;
&#xD;
             a. Patients who have been vaccinated for hepatitis B and do not have a history of&#xD;
             infection are eligible.&#xD;
&#xD;
         12. Female patients who are pregnant or breastfeeding&#xD;
&#xD;
         13. Women of child-bearing potential and their male partners who are unwilling or unable&#xD;
             to use an acceptable method of birth control for the entire study period. Acceptable&#xD;
             methods of contraception are those that, alone or in combination, result in a failure&#xD;
             rate of &lt; 1% per year when used consistently and correctly&#xD;
&#xD;
         14. Any condition for which, in the opinion of the investigator, participation would not&#xD;
             be in the best interest of the participant (e.g., compromise the well-being) or that&#xD;
             could prevent, limit, or confound the protocol-specified assessments&#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>Eugene J Koay</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Eugene J Koay</last_name>
    <phone>713-563-2381</phone>
    <email>ekoay@mdanderson.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eugene J. Koay</last_name>
      <phone>713-563-2381</phone>
      <email>EKoay@mdanderson.org</email>
    </contact>
    <investigator>
      <last_name>Eugene J. Koay</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>September 14, 2023</last_update_submitted>
  <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 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>Adenocarcinoma</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_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/NCT04484909
org study id: 2019-1001
secondary id: NCI-2020-03731
secondary id: 2019-1001
nct id: NCT04484909
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To find the recommended dose of NBTXR3 that can be given in combination with radiation
      therapy to patients with pancreatic cancer. To learn if the dose NBTXR3 found in Part 1 can
      help to control the disease.
PRIMARY OBJECTIVE:

      • To determine the recommended phase II dose (RP2D) of NBTXR3 activated by radiotherapy in
      subjects with locally advanced or borderline-resectable pancreatic ductal adenocarcinoma.

      SECONDARY OBJECTIVES:

        -  To evaluate the safety and feasibility of NBTXR3 intratumoral injection activated by
           radiotherapy in locally advanced or borderline-resectable pancreatic ductal
           adenocarcinoma

        -  To evaluate the anti-tumor response of NBTXR3 intratumoral injection activated by
           radiotherapy in subjects with locally advanced or borderline-resectable pancreatic
           ductal adenocarcinoma

        -  To evaluate time-to-event outcomes in subjects with locally advanced or
           borderline-resectable pancreatic ductal adenocarcinoma

      EXPLORATORY OBJECTIVES:

        -  To evaluate the body kinetic profile of intratumorally injected NBTXR3.

        -  To evaluate time to event outcomes for subjects with clinical staging of locally
           advanced, unresectable disease.

        -  To evaluate resectability conversion rates.

        -  To evaluate surgical outcomes in subjects who undergo surgery after radiation therapy.

        -  To associate radiomic measurements with outcomes.

        -  To evaluate biomarkers of response in subjects treated with NBTXR3/RT.

      OUTLINE: This is a dose-escalation study of NBTXR3.

      Patients receive NBTXR3 intratumorally (IT) on day 1. Patients then undergo 15 fractions of
      intensity modulated radiation therapy (IMRT) between days 15-43 in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 1 month and then every 3
      months for up to 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-limiting toxicities
time frame: 4 weeks after last radiation dose
description: Any grade >= 3 adverse event related to NBTXR3 and/or radiation therapy. Any toxicity (grade >= 3) that is at least possibly related to study drug (NBTXR3) is a DLT. Adverse events will be scored based on National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0).
measure: Maximum tolerated dose (MTD)
time frame: Up to 1 year
description: MTD will be determined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate 30%.
measure: Recommended phase II dose (RP2D)
time frame: Up to 1 year
measure: Determination of the feasibility of NBTXR3 injection in pancreas
time frame: Up to 1 year
description: Feasibility refers to the ability to do intratumoral injection of NBTXR3. The outcome for each patient would be "feasible" or "not feasible."
measure: Progression free survival (PFS)
time frame: From NBTXR3 injection to local recurrence, local progression, distant progression, or death from any cause, whichever occurs first, assessed up to 1 year
measure: Overall survival (OS)
time frame: From NBTXR3 injection to death from any cause or EoS, whichever occurs first, assessed up to 1 year
measure: Presence of hafnium
time frame: Up to 1 year
description: Will evaluation of the time-course dependent presence of hafnium in blood and urine following NBTXR3 intratumoral injection.
measure: Disease control rate
time frame: 6 months
description: Defined as the proportion of patients without progression 6 months post NBTXR3 injection.
measure: Proportion of locally advanced subjects who undergo surgical resection after receiving NBTXR3/radiation therapy (R3/RT)
time frame: Up to 1 year
measure: Resection status
time frame: Up to 1 year
description: Resection status as assessed macroscopically by surgeon R0- Macroscopically complete tumor removal with negative microscopic surgical margins, R1- Macroscopically complete tumor removal with positive microscopic margins (any or all), and R2- Macroscopically incomplete tumor removal with known or suspected residual gross disease.
arm group label: Treatment (NBTXR3, radiation therapy)
arm group type: Experimental
description: Patients receive NBTXR3 IT on day 1. Patients then undergo 15 fractions of radiation therapy between days 15-43 in the absence of disease progression or unacceptable toxicity.
intervention type: Other
intervention name: Hafnium Oxide-containing Nanoparticles NBTXR3
description: Given IT
arm group label: Treatment (NBTXR3, radiation therapy)
other name: NBTXR3
intervention type: Radiation
intervention name: Radiation Therapy
description: Undergo radiation therapy
arm group label: Treatment (NBTXR3, radiation therapy)
other name: Cancer Radiotherapy
other name: Irradiate
other name: Irradiated
other name: Irradiation
other name: Radiation
other name: Radiation Therapy, NOS
other name: Radiotherapeutics
other name: Radiotherapy
other name: RT
other name: Therapy, Radiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eugene J Koay
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
last name: Eugene J Koay
phone: 713-563-2381
email: ekoay@mdanderson.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Pancreatic Neoplasms