<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/NCT03778879</url>
  </required_header>
  <id_info>
    <org_study_id>UGIP18131</org_study_id>
    <nct_id>NCT03778879</nct_id>
  </id_info>
  <brief_title>Pre-operative Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma With or Without CCX872-B</brief_title>
  <official_title>A Phase 1b Trial of Neoadjuvant Stereotactic Body Radiotherapy With or Without CCR2 Inhibitor (CCX872-B) Immunotherapy for Preoperative Treatment of Resectable Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alan Katz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Rochester</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Standard treatment for newly diagnosed operable pancreatic cancer usually involves undergoing&#xD;
      surgery first and then receiving chemotherapy with or without radiation therapy. However, the&#xD;
      pancreatic cancer often comes back after this treatment. Therefore, the investigators are&#xD;
      studying whether giving treatment prior to surgery can help decrease the risk the cancer&#xD;
      returns.&#xD;
&#xD;
      Stereotactic Body Radiation Therapy (SBRT) is a highly focused type of radiation therapy&#xD;
      commonly used in the treatment of pancreatic cancer. This treatment has been shown to be safe&#xD;
      and effective for the preoperative treatment of pancreatic cancer. The purpose of this study&#xD;
      is to determine if combining an experimental drug, CCX872-B, with SBRT continues to be safe&#xD;
      and whether the combination treatment may be more effective at boosting the participant's&#xD;
      immune system's ability to kill the pancreatic cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators have shown that preoperative SBRT followed by surgical resection is&#xD;
      feasible and safe in patients in the previous trial UGIP14107. The investigators have also&#xD;
      presented preclinical evidence that inhibiting entry of CCR2+ IM using a small molecule&#xD;
      antagonist against CCR2 results in enhanced efficacy of RT 26. The investigators hypothesize&#xD;
      that inhibition of the CCR2 axis can potentially up regulate the immune response following&#xD;
      radiation, therefore leading to a more robust tumor killing response. In preclinical studies,&#xD;
      CCR2 inhibitor has little effect in the absence of RT, therefore, the investigators are not&#xD;
      including a drug therapy alone group. To test this hypothesis, a phase Ib clinical trial has&#xD;
      been proposed to evaluate the effect of combining stereotactic body radiotherapy with CCR2&#xD;
      inhibition in the neoadjuvant treatment of surgically resectable adenocarcinoma of the head&#xD;
      of the pancreas.&#xD;
&#xD;
      The study will consist of two parts in sequential fashion. The first fifteen patients will be&#xD;
      assigned to Group 1 and undergo SBRT with CCR2 inhibitor CCX872-B. The primary objective is&#xD;
      to establish safety and feasibility of the treatment and analyze biomarkers to determine if&#xD;
      combined treatment can stimulate an immune response in human patients. A second group of 5&#xD;
      patients will undergo SBRT alone as a comparison group for biomarker immune response.&#xD;
&#xD;
      The investigators would like to proceed with SBRT and CCX872-B as Group 1 given the&#xD;
      investigators already have sufficient data from UGIP14107 to show that SBRT is safe and&#xD;
      feasible and studying the combination of SBRT with CCX872-B is the primary scientific&#xD;
      objective of this study. If unexpected safety issues occur with Group 1, the investigators&#xD;
      would consider closing trial at that time without enrolling any patients in Group 2 which&#xD;
      would reduce the number of patients exposed to the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    CCX872-B will not be available in sufficient quantity to conduct the study.&#xD;
  </why_stopped>
  <start_date type="Anticipated">August 1, 2019</start_date>
  <completion_date type="Anticipated">August 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Percentage of patients who complete radiation therapy, drug treatment and surgery</measure>
    <time_frame>6 weeks</time_frame>
    <description>Number of patients who proceed through radiation and drug treatment and undergo surgical resection in a timely manner.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of patients who are ineligible for surgical resection due to toxicity from SBRT + CCX872-B or SBRT alone</measure>
    <time_frame>12 weeks</time_frame>
    <description>Assessment of whether patients are made ineligible for surgical resection solely due to toxicities from SBRT + CCX872-B or SBRT alone.&#xD;
Measure of Grade 3 toxicity directly attributable to SBRT+ CCX872-B or SBRT alone.&#xD;
Analyze rate of grade 2 or greater acute toxicity caused by SBRT with or without CCX872-B.&#xD;
Determination of intraoperative and postoperative surgical morbidity following neoadjuvant treatment including the amount of fibrosis and total operative time.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with no further growth of cancer at original site</measure>
    <time_frame>2 years</time_frame>
    <description>Count subjects with no further growth of cancer at original site</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with recurrence of cancer in other body sites</measure>
    <time_frame>2 years</time_frame>
    <description>Compare recurrence locations (metastases to other organs or non-regional adenopathy) of treated patients relative to historical controls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean time to progression of pancreatic cancer</measure>
    <time_frame>4 years</time_frame>
    <description>Duration of progression free survival of treated patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean time to death</measure>
    <time_frame>4 years</time_frame>
    <description>Measure duration of survival of treated patients</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Adenocarcinoma of the Pancreas</condition>
  <condition>Pancreas Cancer</condition>
  <arm_group>
    <arm_group_label>Group 1:With CCX872-B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Concurrent SBRT 25 Gy in 5 fractions over 5-7 days, and 21 days of CCX872-B therapy. CCX872-B 150 mg by mouth twice daily approximately 12 hours apart.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2:Without CCX872-B</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>SBRT Alone: 25 Gy in 5 fractions over 5-7 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CCX872-B</intervention_name>
    <description>CCX872-B concurrent with stereotactic body radiation therapy for pancreatic adenocarcinoma.</description>
    <arm_group_label>Group 1:With CCX872-B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient with pathologically proven diagnosis of adenocarcinoma of the head of the&#xD;
             pancreas&#xD;
&#xD;
          2. CT w/ contrast or MRI of the abdomen and pelvis with contrast within 6 weeks prior to&#xD;
             registration&#xD;
&#xD;
          3. CT chest or PET/CT within 6 weeks prior to registration&#xD;
&#xD;
          4. Clinically determined to be resectable based on NCCN Criteria 3.2017: No arterial&#xD;
             tumor contact (celiac axis, superior mesenteric artery or common hepatic artery) and&#xD;
             no tumor contact with the superior mesenteric vein or portal vein, or &lt; 180 degrees&#xD;
             contact without vein contour irregularity&#xD;
&#xD;
          5. No evidence of metastatic disease and/or non-regional lymph node metastases&#xD;
&#xD;
          6. Adequate cardiopulmonary reserves to tolerate surgery&#xD;
&#xD;
          7. ECOG performance status 0-2&#xD;
&#xD;
          8. Adequate bone marrow function defined as follows: White blood cell&gt; 3000cells/mm^3,&#xD;
             Absolute neutrophil count (ANC) ≥ 1500 cells/mm3, Platelets ≥ 100,000 cells/mm3,&#xD;
             Hemoglobin ≥ 9.0 g/dl&#xD;
&#xD;
          9. Male or female subjects, aged at least 18 years; Female subjects of childbearing&#xD;
             potential may participate if adequate contraception is used during, and for at least&#xD;
             the three months after study completion; Male subjects with partners of childbearing&#xD;
             potential may participate in the study if they had a vasectomy at least 6 months prior&#xD;
             to randomization or if adequate contraception is used during, and for at least the&#xD;
             three months after study completion; Adequate contraception is defined as resulting in&#xD;
             a failure rate of less than 1% per year&#xD;
&#xD;
         10. Patient must sign study specific informed consent prior to study entry&#xD;
&#xD;
         11. Anticipated life expectancy ≥ 12 weeks; -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior surgical resection of any pancreatic malignancy&#xD;
&#xD;
          2. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free&#xD;
             for a minimum of 3 years&#xD;
&#xD;
          3. Any prior systemic or radiation treatment, including investigational treatments, of&#xD;
             the patient's pancreatic tumor.&#xD;
&#xD;
          4. Prior radiotherapy to the region of pancreatic cancer that would result in overlap of&#xD;
             radiation therapy fields&#xD;
&#xD;
          5. Severe, active comorbidity, defined as follows:&#xD;
&#xD;
               1. Unstable angina and/or congestive heart failure requiring hospitalization within&#xD;
                  the last 6 months&#xD;
&#xD;
               2. Transmural myocardial infarction within the last 6 months&#xD;
&#xD;
               3. Clinically significant ECG abnormalities e.g. QTcF &gt;450msec&#xD;
&#xD;
               4. Acute viral, bacterial or fungal infection requiring intravenous antibiotics at&#xD;
                  the within 4 weeks of registration&#xD;
&#xD;
               5. Known active HIV, HBV or HCV infections&#xD;
&#xD;
               6. Chronic obstructive pulmonary disease exacerbation or other respiratory illness&#xD;
                  requiring hospitalization or precluding study therapy within 30 days prior to&#xD;
                  registration.&#xD;
&#xD;
               7. Uncontrolled diabetes or hypertension&#xD;
&#xD;
               8. Serious psychiatric illness or altered mental status&#xD;
&#xD;
          6. Severe, uncorrectable hepatic insufficiency and/or coagulation defects due to liver&#xD;
             failure&#xD;
&#xD;
          7. Any evidence of distant metastases (M1)&#xD;
&#xD;
          8. (ONLY applies for Group 1 patients taking CCX872-B )Taking agents known to be strong&#xD;
             inhibitors or inducers of CYP3A4 or UGT1A1 within 2 weeks prior to Day 1 dosing; these&#xD;
             include atazanavir, boceprevir, clarithromycin, conivaptan, gemfibrozil, grapefruit&#xD;
             juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil,&#xD;
             nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir,&#xD;
             telithromycin, voriconazole, rifampin, and carbamazepine; use of these drugs must be&#xD;
             avoided during the study and until 2 weeks after stopping CCX872-B treatment -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>December 15, 2018</study_first_submitted>
  <study_first_submitted_qc>December 15, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>July 17, 2019</last_update_submitted>
  <last_update_submitted_qc>July 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Rochester</investigator_affiliation>
    <investigator_full_name>Alan Katz</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Adenocarcinoma</keyword>
  <keyword>Pancreas</keyword>
  <keyword>Radiation Therapy</keyword>
  <keyword>CCX872-B</keyword>
  <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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03778879
org study id: UGIP18131
nct id: NCT03778879
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Standard treatment for newly diagnosed operable pancreatic cancer usually involves undergoing
      surgery first and then receiving chemotherapy with or without radiation therapy. However, the
      pancreatic cancer often comes back after this treatment. Therefore, the investigators are
      studying whether giving treatment prior to surgery can help decrease the risk the cancer
      returns.

      Stereotactic Body Radiation Therapy (SBRT) is a highly focused type of radiation therapy
      commonly used in the treatment of pancreatic cancer. This treatment has been shown to be safe
      and effective for the preoperative treatment of pancreatic cancer. The purpose of this study
      is to determine if combining an experimental drug, CCX872-B, with SBRT continues to be safe
      and whether the combination treatment may be more effective at boosting the participant's
      immune system's ability to kill the pancreatic cancer.
The investigators have shown that preoperative SBRT followed by surgical resection is
      feasible and safe in patients in the previous trial UGIP14107. The investigators have also
      presented preclinical evidence that inhibiting entry of CCR2+ IM using a small molecule
      antagonist against CCR2 results in enhanced efficacy of RT 26. The investigators hypothesize
      that inhibition of the CCR2 axis can potentially up regulate the immune response following
      radiation, therefore leading to a more robust tumor killing response. In preclinical studies,
      CCR2 inhibitor has little effect in the absence of RT, therefore, the investigators are not
      including a drug therapy alone group. To test this hypothesis, a phase Ib clinical trial has
      been proposed to evaluate the effect of combining stereotactic body radiotherapy with CCR2
      inhibition in the neoadjuvant treatment of surgically resectable adenocarcinoma of the head
      of the pancreas.

      The study will consist of two parts in sequential fashion. The first fifteen patients will be
      assigned to Group 1 and undergo SBRT with CCR2 inhibitor CCX872-B. The primary objective is
      to establish safety and feasibility of the treatment and analyze biomarkers to determine if
      combined treatment can stimulate an immune response in human patients. A second group of 5
      patients will undergo SBRT alone as a comparison group for biomarker immune response.

      The investigators would like to proceed with SBRT and CCX872-B as Group 1 given the
      investigators already have sufficient data from UGIP14107 to show that SBRT is safe and
      feasible and studying the combination of SBRT with CCX872-B is the primary scientific
      objective of this study. If unexpected safety issues occur with Group 1, the investigators
      would consider closing trial at that time without enrolling any patients in Group 2 which
      would reduce the number of patients exposed to the study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of patients who complete radiation therapy, drug treatment and surgery
time frame: 6 weeks
description: Number of patients who proceed through radiation and drug treatment and undergo surgical resection in a timely manner.
measure: Percentage of patients who are ineligible for surgical resection due to toxicity from SBRT + CCX872-B or SBRT alone
time frame: 12 weeks
description: Assessment of whether patients are made ineligible for surgical resection solely due to toxicities from SBRT + CCX872-B or SBRT alone.
Measure of Grade 3 toxicity directly attributable to SBRT+ CCX872-B or SBRT alone.
Analyze rate of grade 2 or greater acute toxicity caused by SBRT with or without CCX872-B.
Determination of intraoperative and postoperative surgical morbidity following neoadjuvant treatment including the amount of fibrosis and total operative time.
measure: Number of participants with no further growth of cancer at original site
time frame: 2 years
description: Count subjects with no further growth of cancer at original site
measure: Number of subjects with recurrence of cancer in other body sites
time frame: 2 years
description: Compare recurrence locations (metastases to other organs or non-regional adenopathy) of treated patients relative to historical controls
measure: Mean time to progression of pancreatic cancer
time frame: 4 years
description: Duration of progression free survival of treated patients
measure: Mean time to death
time frame: 4 years
description: Measure duration of survival of treated patients
arm group label: Group 1:With CCX872-B
arm group type: Experimental
description: Concurrent SBRT 25 Gy in 5 fractions over 5-7 days, and 21 days of CCX872-B therapy. CCX872-B 150 mg by mouth twice daily approximately 12 hours apart.
arm group label: Group 2:Without CCX872-B
arm group type: No Intervention
description: SBRT Alone: 25 Gy in 5 fractions over 5-7 days
intervention type: Drug
intervention name: CCX872-B
description: CCX872-B concurrent with stereotactic body radiation therapy for pancreatic adenocarcinoma.
arm group label: Group 1:With CCX872-B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Rochester
investigator full name: Alan Katz
investigator title: Associate Professor
mesh term: Adenocarcinoma
mesh term: Pancreatic Neoplasms
sharing ipd: No