<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/NCT03777462</url>
  </required_header>
  <id_info>
    <org_study_id>ChanghaiH-PP04</org_study_id>
    <nct_id>NCT03777462</nct_id>
  </id_info>
  <brief_title>Borderline Resectable Pancreatic Cancer Neoadjuvant Chemoradiotherapy Clinicaltrial-1</brief_title>
  <acronym>BRPCNCC-1</acronym>
  <official_title>Comparisons of Different Neoadjuvant Chemotherapy Regimens With or Without Stereotactic Body Radiation Therapy for Borderline Resectable Pancreatic Cancer: Study Protocol of a Prospective, Randomized Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Changhai Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Changhai Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is to investigate whether neoadjuvant chemotherapy plus SBRT results in better&#xD;
      outcomes compared with neoadjuvant chemotherapy alone and also compare the efficacy of&#xD;
      gemcitabine plus nab-paclitaxel with SBRT and S-1 plus nab-paclitaxel with SBRT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a Phase II clinical trial that investigate whether neoadjuvant&#xD;
      chemotherapy plus SBRT results in better outcomes compared with neoadjuvant chemotherapy&#xD;
      alone and also compare the efficacy of gemcitabine plus nab-paclitaxel with SBRT and S-1 plus&#xD;
      nab-paclitaxel with SBRT. It is known that neoadjuvant therapy is vital for improved&#xD;
      survival, which has been confirmed in previous studies that neoadjuvant chemotherapy with or&#xD;
      without radiotherapy provides superior overall compared with upfront surgery. However,&#xD;
      question of whether the addition of radiotherapy to neoadjuvant chemotherapy can improve&#xD;
      prognosis compared with chemotherapy alone is a challenging matter. Also, no studies have&#xD;
      evaluated the efficacy of S-1 as the neoadjuvant chemotherapy regimen for BRPC albeit similar&#xD;
      prognosis has been found between S-1 and gemcitabine in advanced pancreatic cancer. In this&#xD;
      trial, patients with biopsy and radiographically confirmed BRPC will be randomly allocated&#xD;
      into three groups: neoadjuvant gemcitabine plus nab-paclitaxel, neoadjuvant gemcitabine plus&#xD;
      nab-paclitaxel with SBRT and neoadjuvant S-1 plus nab-paclitaxel with SBRT. Surgical&#xD;
      resection will be performed 3 weeks after SBRT. The primary endpoint is overall survival. The&#xD;
      secondary outcomes are progression free survival, pathological complete response rate, R0&#xD;
      resection rate and incidence of adverse effects. If results show the survival benefits of&#xD;
      neoadjuvant chemotherapy plus SBRT and similar outcomes between S-1 and gemcitabine, it may&#xD;
      provide evidence of clinical practice of this modality for BRPC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall time</measure>
    <time_frame>From date of randomization until the date of death from any cause, whichever came first, assessed up to 24 months</time_frame>
    <description>The time between operation and the death of patients</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease free time</measure>
    <time_frame>From date of randomization until the date of first documented progression or metastasis, assessed up to 12 months</time_frame>
    <description>The time between operation and the relapse or metastasis of tumors</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Group A of neoadjuvant chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Neoadjuvant gemcitabine plus nab-paclitaxel is used in this group. Intravenous administration of gemcitabine (1000mg/m2) and nab-paclitaxel (125 mg/m2) are initiated on day 1, 8 and 15 during each 4-week cycle, which will repeat for 3 cycles. And surgical resection is performed after completion of the whole chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B of neoadjuvant chemoradiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT is used in this group. Intravenous administration of gemcitabine (1000mg/m2) and nab-paclitaxel (125 mg/m2) are initiated on day 1, 8 and 15 during each 4-week cycle, which will repeat for 3 cycles. After completion of the whole chemotherapy, patients will first receive PET-CT to exclude distant metastases and then undergo SBRT. The prescribed dose is 7.5-8Gy/f for 5 fractions. Dose constraints of normal tissues are referred to the American Association of Physicists in Medicine guidelines in TG-101. And surgical resection is performed 3 weeks after SBRT.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C of neoadjuvant chemoradiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Neoadjuvant S-1 plus nab-paclitaxel with SBRT is used in this group. Intravenous administration of nab-paclitaxel (125 mg/m2) is initiated on day 1, 8 and 15 during each 4-week cycle, which will repeat for 3 cycles. And S-1 is orally administrated at a dose of 80 mg/m2 for 18 days followed by a 10-day rest during each 4-week cycle, which aslo continues for 3 cycles. After completion of the whole chemotherapy, patients will first receive PET-CT to exclude distant metastases and then undergo SBRT. The prescribed dose is 7.5-8Gy/f for 5 fractions. Dose constraints of normal tissues are referred to the American Association of Physicists in Medicine guidelines in TG-101. And surgical resection is performed 3 weeks after SBRT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Neoadjuvant gemcitabine plus nab-paclitaxel</intervention_name>
    <description>Neoadjuvant gemcitabine plus nab-paclitaxel is used in the intervention group for 3 cycles. Standard doses of gemcitabine and nab-paclitaxel are adopted. Surgical resection will be performed after neoadjuvant chemotherapy.</description>
    <arm_group_label>Group A of neoadjuvant chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT</intervention_name>
    <description>Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT is used in the intervention group for 3 cycles. Standard doses of gemcitabine and nab-paclitaxel are adopted. The radiation dose of SBRT is 7.5-8Gy/f for 5 fractions. Surgical resection will be performed 3 weeks after SBRT.</description>
    <arm_group_label>Group B of neoadjuvant chemoradiotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Neoadjuvant S-1 plus nab-paclitaxel with SBRT</intervention_name>
    <description>Neoadjuvant S-1 plus nab-paclitaxel with SBRT is used in the intervention group for 3 cycles. Standard doses of gemcitabine and nab-paclitaxel are adopted. The radiation dose of SBRT is 7.5-8Gy/f for 5 fractions. Surgical resection will be performed 3 weeks after SBRT.</description>
    <arm_group_label>Group C of neoadjuvant chemoradiotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age≥18 years old and ≤80 years old;&#xD;
&#xD;
          -  Histological proven pancreatic adenocarcinoma;&#xD;
&#xD;
          -  Borderline resectable pancreatic cancer proven by imaging examinations via&#xD;
             multidisciplinary approaches according to NCCN guidelines;&#xD;
&#xD;
          -  No prior chemotherapy or radiotherapy;&#xD;
&#xD;
          -  ECOG of 0 or 1;&#xD;
&#xD;
          -  Routine blood test: absolute neutrophil count&gt;1500/mm3, platelet&gt;100000/mm3;&#xD;
&#xD;
          -  Normal liver function: serum total bilirubin≤2.0mg/dl, ALT and AST&lt;2.5 times of the&#xD;
             upper limit of normal value;&#xD;
&#xD;
          -  Normal kidney function: serum creatinine&lt;1.5 times of the upper limit of normal value&#xD;
             or creatinine clearance rate&gt;45ml/min;&#xD;
&#xD;
          -  No severe comorbidities.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Metastatic pancreatic cancer;&#xD;
&#xD;
          -  Patients who had surgeries, chemotherapy or other treatments before inclusion;&#xD;
&#xD;
          -  Impaired organ functions: heart failure (New York Heart Association III-IV), coronary&#xD;
             heart disease, myocardial infarction within 6 months, severe cardiac arrhythmia and&#xD;
             respiratory failure;&#xD;
&#xD;
          -  Confirmed other cancer within 5 years;&#xD;
&#xD;
          -  Pregnant women or lactating women;&#xD;
&#xD;
          -  Patients enrolled in other clinical trials or incompliant of regular follow up;&#xD;
&#xD;
          -  Patients who did not provide an informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gang Jin, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Changhai Hospital, Shanghai, China</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shiwei Guo, Doctor</last_name>
    <phone>+8618621500666</phone>
    <email>gestwa@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Suizhi Gao, Master</last_name>
    <phone>+8613167137990</phone>
    <email>gaosuizhi@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Changhai Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200433</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shiwei Guo, Doctor</last_name>
      <phone>+8618621500666</phone>
      <email>gestwa@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Suizhi Gao, Master</last_name>
      <phone>+8613167137990</phone>
      <email>gaosuizhi@163.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>August 31, 2023</last_update_submitted>
  <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Changhai Hospital</investigator_affiliation>
    <investigator_full_name>Guo ShiWei</investigator_full_name>
    <investigator_title>Research assistant of Hepatobiliary and Pancreatic Surgery</investigator_title>
  </responsible_party>
  <keyword>pancreatic cancer</keyword>
  <keyword>neoadjuvant chemotherapy</keyword>
  <keyword>SBRT</keyword>
  <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>
    <mesh_term>Gemcitabine</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/NCT03777462
org study id: ChanghaiH-PP04
nct id: NCT03777462
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is to investigate whether neoadjuvant chemotherapy plus SBRT results in better
      outcomes compared with neoadjuvant chemotherapy alone and also compare the efficacy of
      gemcitabine plus nab-paclitaxel with SBRT and S-1 plus nab-paclitaxel with SBRT.
This research study is a Phase II clinical trial that investigate whether neoadjuvant
      chemotherapy plus SBRT results in better outcomes compared with neoadjuvant chemotherapy
      alone and also compare the efficacy of gemcitabine plus nab-paclitaxel with SBRT and S-1 plus
      nab-paclitaxel with SBRT. It is known that neoadjuvant therapy is vital for improved
      survival, which has been confirmed in previous studies that neoadjuvant chemotherapy with or
      without radiotherapy provides superior overall compared with upfront surgery. However,
      question of whether the addition of radiotherapy to neoadjuvant chemotherapy can improve
      prognosis compared with chemotherapy alone is a challenging matter. Also, no studies have
      evaluated the efficacy of S-1 as the neoadjuvant chemotherapy regimen for BRPC albeit similar
      prognosis has been found between S-1 and gemcitabine in advanced pancreatic cancer. In this
      trial, patients with biopsy and radiographically confirmed BRPC will be randomly allocated
      into three groups: neoadjuvant gemcitabine plus nab-paclitaxel, neoadjuvant gemcitabine plus
      nab-paclitaxel with SBRT and neoadjuvant S-1 plus nab-paclitaxel with SBRT. Surgical
      resection will be performed 3 weeks after SBRT. The primary endpoint is overall survival. The
      secondary outcomes are progression free survival, pathological complete response rate, R0
      resection rate and incidence of adverse effects. If results show the survival benefits of
      neoadjuvant chemotherapy plus SBRT and similar outcomes between S-1 and gemcitabine, it may
      provide evidence of clinical practice of this modality for BRPC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall time
time frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 24 months
description: The time between operation and the death of patients
measure: Disease free time
time frame: From date of randomization until the date of first documented progression or metastasis, assessed up to 12 months
description: The time between operation and the relapse or metastasis of tumors
arm group label: Group A of neoadjuvant chemotherapy
arm group type: Active Comparator
description: Neoadjuvant gemcitabine plus nab-paclitaxel is used in this group. Intravenous administration of gemcitabine (1000mg/m2) and nab-paclitaxel (125 mg/m2) are initiated on day 1, 8 and 15 during each 4-week cycle, which will repeat for 3 cycles. And surgical resection is performed after completion of the whole chemotherapy.
arm group label: Group B of neoadjuvant chemoradiotherapy
arm group type: Experimental
description: Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT is used in this group. Intravenous administration of gemcitabine (1000mg/m2) and nab-paclitaxel (125 mg/m2) are initiated on day 1, 8 and 15 during each 4-week cycle, which will repeat for 3 cycles. After completion of the whole chemotherapy, patients will first receive PET-CT to exclude distant metastases and then undergo SBRT. The prescribed dose is 7.5-8Gy/f for 5 fractions. Dose constraints of normal tissues are referred to the American Association of Physicists in Medicine guidelines in TG-101. And surgical resection is performed 3 weeks after SBRT.
arm group label: Group C of neoadjuvant chemoradiotherapy
arm group type: Experimental
description: Neoadjuvant S-1 plus nab-paclitaxel with SBRT is used in this group. Intravenous administration of nab-paclitaxel (125 mg/m2) is initiated on day 1, 8 and 15 during each 4-week cycle, which will repeat for 3 cycles. And S-1 is orally administrated at a dose of 80 mg/m2 for 18 days followed by a 10-day rest during each 4-week cycle, which aslo continues for 3 cycles. After completion of the whole chemotherapy, patients will first receive PET-CT to exclude distant metastases and then undergo SBRT. The prescribed dose is 7.5-8Gy/f for 5 fractions. Dose constraints of normal tissues are referred to the American Association of Physicists in Medicine guidelines in TG-101. And surgical resection is performed 3 weeks after SBRT.
intervention type: Drug
intervention name: Neoadjuvant gemcitabine plus nab-paclitaxel
description: Neoadjuvant gemcitabine plus nab-paclitaxel is used in the intervention group for 3 cycles. Standard doses of gemcitabine and nab-paclitaxel are adopted. Surgical resection will be performed after neoadjuvant chemotherapy.
arm group label: Group A of neoadjuvant chemotherapy
intervention type: Drug
intervention name: Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT
description: Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT is used in the intervention group for 3 cycles. Standard doses of gemcitabine and nab-paclitaxel are adopted. The radiation dose of SBRT is 7.5-8Gy/f for 5 fractions. Surgical resection will be performed 3 weeks after SBRT.
arm group label: Group B of neoadjuvant chemoradiotherapy
intervention type: Drug
intervention name: Neoadjuvant S-1 plus nab-paclitaxel with SBRT
description: Neoadjuvant S-1 plus nab-paclitaxel with SBRT is used in the intervention group for 3 cycles. Standard doses of gemcitabine and nab-paclitaxel are adopted. The radiation dose of SBRT is 7.5-8Gy/f for 5 fractions. Surgical resection will be performed 3 weeks after SBRT.
arm group label: Group C of neoadjuvant chemoradiotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Gang Jin, Doctor
role: Principal Investigator
affiliation: Changhai Hospital, Shanghai, China
last name: Shiwei Guo, Doctor
phone: +8618621500666
email: gestwa@163.com
last name: Suizhi Gao, Master
phone: +8613167137990
email: gaosuizhi@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Changhai Hospital
investigator full name: Guo ShiWei
investigator title: Research assistant of Hepatobiliary and Pancreatic Surgery
mesh term: Pancreatic Neoplasms
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel
mesh term: Gemcitabine