xml: <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/NCT05988372</url>
    </required_header>
    <id_info>
      <org_study_id>LAPC2023</org_study_id>
      <nct_id>NCT05988372</nct_id>
    </id_info>
    <brief_title>Sulfatinib and Serplulimab Combined With AG Regimen as Conversion Therapy for Patients With Locally Advanced Pancreatic Cancer : A Single-arm, Phase II Study(SAGE)</brief_title>
    <official_title>Sulfatinib and Serplulimab Combined With Albumin-paclitaxel and Gemcitabine Regimen as Conversion Therapy for Patients With Locally Advanced Pancreatic Cancer : A Single-arm, Phase II Study(SAGE)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sun Yat-sen University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sun Yat-sen University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a phase 2, single-arm clinical study. The purpose of this study is to explore the&#xD;
        efficacy and safety of sulfatinib and serplulimab in combination with gemcitabine and&#xD;
        albumin-paclitaxel in the conversion therapy for patients with unresectable locally advanced&#xD;
        pancreatic cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The trial will recruit 42 patients. Enrolled patients received sulfatinib in combination with&#xD;
        serplulimab and AG regimen chemotherapy. Within 6 cycles of conversion therapy, the&#xD;
        investigator will assess whether the patient has potential R0 resection possibility according&#xD;
        to imaging results every 2 cycles (±7 days). For patients who underwent R0 resection,&#xD;
        adjuvant therapy with sulfatinib combined with serplulimab and AG regimen was performed&#xD;
        within 12 weeks after surgery, and the adjuvant therapy before and after surgery was&#xD;
        performed for a total of 6 cycles. Perioperative treatment lasted about 6 months, followed by&#xD;
        sulfatinib combined with serplulimab for 1 year. Patients who cannot undergo surgery or have&#xD;
        R1, R2 resection will be given sulfatinib combined with serplulimab for maintenance treatment&#xD;
        up to 2 years, or until intolerance, disease progression, death or other criteria specified&#xD;
        in the protocol for discontinuation of study treatment are met.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 30, 2023</start_date>
    <completion_date type="Anticipated">August 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 30, 2023</primary_completion_date>
    <phase>Phase 2</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>R0 Surgical Resection Rate</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Proportion of patients with negative microscopic margins (no tumor cell remains)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Surgical conversion rate</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Surgical conversion rate: the proportion of patients with successful conversion and surgical resection in all patients, surgical conversion rate =(number of patients with successful conversion and surgical resection/total number of patients) ×100%.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>ORR is defined as the percentage of patients who have achieved complete response (CR) or partial response (PR), as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Deepness of response (DpR)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>DpR is defined as the percentage of maximal tumor reduction from baseline of a target lesion.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-Free Survival (PFS)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>PFS is defined as the time from the first dose of administration to progression or death</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease-free survival (DFS)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>DFS is defined as the time interval between the date of enrollment and the date of the first documented evidence of relapse after radical resection at any site or death related to cancer</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Over Survival (OS)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>OS is defined as the time from first treatment to death, regardless of disease recurrence</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">42</enrollment>
    <condition>Locally Advanced Pancreatic Cancer</condition>
    <arm_group>
      <arm_group_label>Sulfatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single-arm trial whereby all consented, enrolled, eligible patients receive Sulfatinib, Serplulimab, Gemcitabine and Albumin-paclitaxel</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Sulfatinib</intervention_name>
      <description>250mg orally once a day for 3 weeks(3 weeks 1 cycle)</description>
      <arm_group_label>Sulfatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Serplulimab</intervention_name>
      <description>4.5mg/Kg by intravenous infusions on day1 every 3 weeks</description>
      <arm_group_label>Sulfatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Albumin-paclitaxel</intervention_name>
      <description>125mg/m2 by intravenous infusions on day1 and 8 every 3 weeks</description>
      <arm_group_label>Sulfatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Gemcitabine</intervention_name>
      <description>1000mg/m2 by intravenous infusions on day1 and 8 every 3 weeks</description>
      <arm_group_label>Sulfatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Written informed consent obtained from the patient prior to treatment.&#xD;
  &#xD;
            2. Pathologically confirmed unresectable locally advanced pancreatic cancer, received no&#xD;
               surgical therapy.&#xD;
  &#xD;
            3. Age between 18 and 75 years at the time of study entry.&#xD;
  &#xD;
            4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.&#xD;
  &#xD;
            5. Measurable or evaluable lesions according to RECIST v1.1 criteria.&#xD;
  &#xD;
            6. Life expectancy ≥ 12 weeks.&#xD;
  &#xD;
            7. There are no serious organic diseases of the heart, lungs, brain and other organs.&#xD;
  &#xD;
            8. Adequate functioning of the bone marrow and major organs function meeting the&#xD;
               following criteria:&#xD;
  &#xD;
                 1. White blood cell count ≥ 4 × 109/L, Neutrophil count ≥ 1.5 × 109/L, Platelets&#xD;
                    count ≥ 100 × 109/L,Hemoglobin ≥ 90 g/L.&#xD;
  &#xD;
                 2. Normal coagulation function, without active bleeding or thrombotic diseases: INR&#xD;
                    ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN.&#xD;
  &#xD;
                 3. Liver function: Total serum bilirubin ≤ 1.5 ×ULN, Serum aspartate&#xD;
                    aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 3 × ULN,&#xD;
                    Obstructive Jaundice with total serum bilirub ≤ 1.5 x ULN after internal/&#xD;
                    external drainage.&#xD;
  &#xD;
                 4. Kidney function: Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or&#xD;
                    creatinine clearance ≥ 60 mL/min.&#xD;
  &#xD;
                 5. Cardiac function:left ventricular ejection fraction (LVEF) of 50%≥ on 2D cardiac&#xD;
                    ultrasound.&#xD;
  &#xD;
            9. Male or female patients of potential for childbearing who voluntarily used effective&#xD;
               contraceptive methods such as double-barrier contraception, condoms, oral or injection&#xD;
               avoidance or pregnancy medications, IUDs, etc during the study period and within 6&#xD;
               months of the last study medication . All female patients will be considered fertile&#xD;
               unless the female patient is naturally menopausal.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Participants diagnosed pancreatic cancer with distant metastases.&#xD;
  &#xD;
            2. Participation in other antineoplastic drug clinical trials within 4 weeks prior to&#xD;
               enrollment;&#xD;
  &#xD;
            3. Previous systemic antitumor therapy (chemotherapy, radiation, targeted or immunoth,&#xD;
               etc.).&#xD;
  &#xD;
            4. Diagnosis of any second malignancy, except for adequately treated basal cell skin&#xD;
               cancer or in situ carcinoma of the cervix uteri.&#xD;
  &#xD;
            5. Known allergy or hypersensitivity to any of the study drugs or any of the study drug&#xD;
               excipients.&#xD;
  &#xD;
            6. Active or prior documented autoimmune or inflammatory disorders.&#xD;
  &#xD;
            7. Participants are being treated with immunosuppressants, or systemic or absorbable&#xD;
               topical hormones for immunosuppressive purposes (dose&gt; 10 mg/day prednisone or other&#xD;
               equivalent hormones) , and the use is still continued within 2 weeks before&#xD;
               enrollment.&#xD;
  &#xD;
            8. Have undergone any surgery (other than biopsy) or invasive treatment or manipulation&#xD;
               within 4 weeks prior to enrollment and the surgical incision has not healed completely&#xD;
               (except intravenous catheterization, puncture drainage, internal or external drainage&#xD;
               of obstructive jaundice, etc.)&#xD;
  &#xD;
            9. Participants with abnormal thyroid function who were unable to maintain thyroid&#xD;
               function within the normal range with medical treatment.&#xD;
  &#xD;
           10. Hypertension that cannot be controlled in the presence of optimal treatment is defined&#xD;
               as systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg.&#xD;
  &#xD;
           11. Urinary routine showed that urinary protein ≥2+, and 24-hour urinary protein&gt;1.0g.&#xD;
  &#xD;
           12. Participantst currently has any disease or condition that affects the absorption of&#xD;
               the drug, or the participants cannot take sulfatinib orally&#xD;
  &#xD;
           13. participants with evidence or history of significant bleeding tendency within 3 months&#xD;
               prior to enrollment (bleeding&gt;30 mL within 3 months with hematemesis, melena,&#xD;
               hematochezia), hemoptysis (fresh blood&gt;5 mL within 4 weeks); Patients with history of&#xD;
               hereditary or acquired bleeding or coagulation dysfunction, with clinically&#xD;
               significant bleeding symptoms or definite bleeding tendency within 3 months, such as&#xD;
               gastrointestinal bleeding and hemorrhagic gastric ulcer.&#xD;
  &#xD;
           14. Cardiovascular disease of significant clinical significance, including but not limited&#xD;
               to acute myocardial infarction, severe/unstable angina, or coronary bypass grafting&#xD;
               within 6 months prior to enrollment; New York Heart Association (NYHA) grade &gt; 2 for&#xD;
               congestive heart failure; ventricular arrhythmias requiring drug therapy;&#xD;
               Electrocardiogram (ECG) showing QT interval ≥480 ms;&#xD;
  &#xD;
           15. Severe infection that is active or uncontrolled:&#xD;
  &#xD;
                 1. Inherited or acquired immunodeficiency disease,&#xD;
  &#xD;
                 2. Known clinically significant history of liver disease, including viral hepatitis&#xD;
                    [known hepatitis B virus (HBV) carriers must exclude active HBV infection , HBV&#xD;
                    DNA positive (&gt;1×104 copies/mL or &gt;2000 IU/ml)];&#xD;
  &#xD;
                 3. known hepatitis C virus infection (HCV) and positive HCV RNA (&gt;1×103 copies/ml)&#xD;
                    or other hepatitis, cirrhosis.&#xD;
  &#xD;
           16. Pregnant or lactating women or participants with family planning during the trial&#xD;
               period.&#xD;
  &#xD;
           17. Participants have a known history of psychotropic substance abuse, alcoholism, or drug&#xD;
               abuse.&#xD;
  &#xD;
           18. The investigator believes that the participant has any clinical or laboratory&#xD;
               abnormalities or other reasons that are unsuitable for this clinical study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Kuang Ming, Ph.D</last_name>
      <phone>008687755766</phone>
      <phone_ext>8576</phone_ext>
      <email>kuangm@mail.sysu.edu.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>First Affiliated Hospital, Sun Yat-Sen University</name>
        <address>
          <city>Guangzhou</city>
          <state>Guangdong</state>
          <zip>510080</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Kuang Ming</last_name>
        <phone>008687755766</phone>
        <phone_ext>8576</phone_ext>
        <email>kuangm@mail.sysu.edu.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 4, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 10, 2023</last_update_submitted>
    <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
      <investigator_full_name>Ming Kuang</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Locally Advanced Pancreatic Cancer</keyword>
    <keyword>Conversion Therapy</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>Gemcitabine</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05988372
  org study id: LAPC2023
  nct id: NCT05988372
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a phase 2, single-arm clinical study. The purpose of this study is to explore the
        efficacy and safety of sulfatinib and serplulimab in combination with gemcitabine and
        albumin-paclitaxel in the conversion therapy for patients with unresectable locally advanced
        pancreatic cancer.
  The trial will recruit 42 patients. Enrolled patients received sulfatinib in combination with
        serplulimab and AG regimen chemotherapy. Within 6 cycles of conversion therapy, the
        investigator will assess whether the patient has potential R0 resection possibility according
        to imaging results every 2 cycles (±7 days). For patients who underwent R0 resection,
        adjuvant therapy with sulfatinib combined with serplulimab and AG regimen was performed
        within 12 weeks after surgery, and the adjuvant therapy before and after surgery was
        performed for a total of 6 cycles. Perioperative treatment lasted about 6 months, followed by
        sulfatinib combined with serplulimab for 1 year. Patients who cannot undergo surgery or have
        R1, R2 resection will be given sulfatinib combined with serplulimab for maintenance treatment
        up to 2 years, or until intolerance, disease progression, death or other criteria specified
        in the protocol for discontinuation of study treatment are met.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: R0 Surgical Resection Rate
  time frame: Up to 2 years
  description: Proportion of patients with negative microscopic margins (no tumor cell remains)
  measure: Surgical conversion rate
  time frame: Up to 2 years
  description: Surgical conversion rate: the proportion of patients with successful conversion and surgical resection in all patients, surgical conversion rate =(number of patients with successful conversion and surgical resection/total number of patients) ×100%.
  measure: Objective response rate (ORR)
  time frame: Up to 2 years
  description: ORR is defined as the percentage of patients who have achieved complete response (CR) or partial response (PR), as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  measure: Deepness of response (DpR)
  time frame: Up to 2 years
  description: DpR is defined as the percentage of maximal tumor reduction from baseline of a target lesion.
  measure: Progression-Free Survival (PFS)
  time frame: Up to 2 years
  description: PFS is defined as the time from the first dose of administration to progression or death
  measure: Disease-free survival (DFS)
  time frame: Up to 2 years
  description: DFS is defined as the time interval between the date of enrollment and the date of the first documented evidence of relapse after radical resection at any site or death related to cancer
  measure: Over Survival (OS)
  time frame: Up to 2 years
  description: OS is defined as the time from first treatment to death, regardless of disease recurrence
  arm group label: Sulfatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine
  arm group type: Experimental
  description: Single-arm trial whereby all consented, enrolled, eligible patients receive Sulfatinib, Serplulimab, Gemcitabine and Albumin-paclitaxel
  intervention type: Drug
  intervention name: Sulfatinib
  description: 250mg orally once a day for 3 weeks(3 weeks 1 cycle)
  arm group label: Sulfatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine
  intervention type: Drug
  intervention name: Serplulimab
  description: 4.5mg/Kg by intravenous infusions on day1 every 3 weeks
  arm group label: Sulfatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine
  intervention type: Drug
  intervention name: Albumin-paclitaxel
  description: 125mg/m2 by intravenous infusions on day1 and 8 every 3 weeks
  arm group label: Sulfatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine
  intervention type: Drug
  intervention name: Gemcitabine
  description: 1000mg/m2 by intravenous infusions on day1 and 8 every 3 weeks
  arm group label: Sulfatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Kuang Ming, Ph.D
  phone: 008687755766
  phone ext: 8576
  email: kuangm@mail.sysu.edu.cn
  facility: 
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Sun Yat-sen University
  investigator full name: Ming Kuang
  investigator title: Professor
  mesh term: Pancreatic Neoplasms
  mesh term: Paclitaxel
  mesh term: Gemcitabine