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/NCT05969171</url>
    </required_header>
    <id_info>
      <org_study_id>IIT-2023-Sufantinib</org_study_id>
      <nct_id>NCT05969171</nct_id>
    </id_info>
    <brief_title>Phase II Study of Sufantinib Combined With AG Versus AG First-line in the Treatment of LAPC or mPC</brief_title>
    <official_title>A Single-center, Randomized Controlled Phase II Study of Sufantinib Combined With Gemcitabine and Abraxane （AG）Versus AG in the First-line Treatment of Locally Advanced or Metastatic Pancreatic Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fudan University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Fudan 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 single-center, open-label randomized controlled Phase II clinical study to observe&#xD;
        and evaluate the efficacy and safety of Sovantinib in combination with AG versus AG&#xD;
        first-line treatment in patients with locally advanced or metastatic pancreatic cancer.&#xD;
  &#xD;
        According to the literature analysis, the mPFS of gemcitabine combined with albumin-binding&#xD;
        paclitaxel in first-line treatment of metastatic pancreatic cancer was 3.56 months in&#xD;
        historical controlled studies, and the expected PFS of soantinib combined with AG regimen&#xD;
        increased from 2.06 months to 4.5 months after 2 cycles of AG regimen. Follow-up time was 12&#xD;
        months and enrollment time was 18 months. α=0.05 and β=0.2 were used for bilateral test, and&#xD;
        the PASS 22 software was used for analysis. The sample size of AG group in the control group&#xD;
        was 29 cases, and that of AG combined with Solvatinib in the experimental group was 29 cases.&#xD;
        The total sample size needed to be enrolled was 58 cases, and a total of 65 subjects were&#xD;
        required according to the 10% shedding rate.&#xD;
  &#xD;
        This study was divided into three stages: screening period, treatment period and follow-up&#xD;
        period. During treatment, tumor status was assessed by imaging every 6 weeks (±7 days) until&#xD;
        disease progression (PD, RECIST 1.1) or death (during patient treatment) or toxicity&#xD;
        intolerance or other protocol criteria for discontinuation of study therapy were met. A&#xD;
        maximum of 6 treatment cycles of AG chemotherapy were specified, and soantinib was continued&#xD;
        until disease progression (PD, RECIST 1.1) or death (during patient treatment) or toxicity&#xD;
        intolerance or other criteria for discontinuation of study therapy were met in the protocol.&#xD;
        Tumor treatment and survival status after disease progression were recorded. Safety outcomes&#xD;
        included AE, changes in laboratory test values, vital signs and electrocardiogram changes.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a single-center, open-label randomized controlled Phase II clinical study to observe&#xD;
        and evaluate the efficacy and safety of solantinib combined with AG versus AG first-line&#xD;
        therapy in patients with locally advanced or metastatic pancreatic cancer.&#xD;
  &#xD;
        According to the literature analysis, the mPFS of gemcitabine combined with albumin-bound&#xD;
        paclitaxel in first-line treatment of metastatic pancreatic cancer in historical control&#xD;
        studies was 3.56 months, and the PFS of solantinib combined with AG regimen was expected to&#xD;
        increase from 2.06 months to 4.5 months after 2 cycles of AG regimen. Follow-up time was 12&#xD;
        months and enrollment time was 18 months. α=0.05 and β=0.2 were used for bilateral test, and&#xD;
        PASS 22 software was used for analysis. The sample size of AG group in the control group was&#xD;
        29 cases, and that of AG combined with solvatinib in the experimental group was 29 cases. The&#xD;
        total sample size required to be enrolled was 58 cases, and a total of 65 subjects were&#xD;
        required according to the calculation of 10% shedding rate.&#xD;
  &#xD;
        The study was divided into three stages: screening period, treatment period and follow-up&#xD;
        period. During treatment, the tumor was evaluated by imaging every 6 weeks (±7 days) until&#xD;
        disease progression (PD, RECIST 1.1) or death (during the patient's treatment) or toxicity&#xD;
        became intolerable or other protocol criteria for discontinuation of study therapy were met.&#xD;
        It is specified that AG chemotherapy should not exceed a maximum of 8 treatment cycles, and&#xD;
        that solantinib should be continued until disease progression (PD, RECIST 1.1) or death (in&#xD;
        the course of patient treatment) or toxicity becomes intolerable or other criteria for&#xD;
        discontinuation of study therapy as specified in the protocol are met. The tumor treatment&#xD;
        and survival status after disease progression were recorded. Safety outcome measures included&#xD;
        AE, changes in laboratory test values, vital signs and electrocardiogram changes.&#xD;
  &#xD;
        Researchers can add unplanned imaging tests for tumors as clinically necessary.&#xD;
  &#xD;
        Subjects must meet all of the following criteria for enrollment:&#xD;
  &#xD;
          1. The subjects voluntarily joined the study and signed the informed consent with good&#xD;
             compliance and follow-up;&#xD;
  &#xD;
          2. Unresectable, locally advanced or metastatic pancreatic cancer confirmed by&#xD;
             histopathology or cytology;&#xD;
  &#xD;
          3. Aged between 18 and 75 (including 18 and 75), male or female;&#xD;
  &#xD;
          4. ECOG score: 0-1; Expected survival ≥12 weeks;&#xD;
  &#xD;
          5. Patients who had previously received 2 cycles of AG regimen first-line systemic therapy&#xD;
             for locally advanced or metastatic pancreatic cancer and whose efficacy was evaluated as&#xD;
             CR, PR, SD (excluding SD patients whose efficacy was evaluated as increased after 2&#xD;
             cycles of therapy);&#xD;
  &#xD;
          6. Patients with postoperative distant metastasis had received adjuvant chemotherapy of one&#xD;
             type and the distance from adjuvant therapy time &amp;gt; Patients with recurrence at 6&#xD;
             months could be included in the group;&#xD;
  &#xD;
          7. At least one measurable lesion (according to RECIST 1.1 criteria); Magnetic resonance&#xD;
             imaging (MRI) enhancement or computed tomography (CT) enhancement accurately measured&#xD;
             the diameter of ≥10mm, conventional CT scan to determine the diameter of at least 20mm.&#xD;
  &#xD;
          8. No serious organic diseases of heart, lung, brain and other organs;&#xD;
  &#xD;
          9. The functions of major organs and bone marrow are basically normal:&#xD;
  &#xD;
               1. Blood routine: white blood cells ≥ 4.0 x 109/L, neutrophils ≥ 1.5 x 109/L,&#xD;
                  platelets ≥ 80 x 109/L, hemoglobin ≥ 90g/L;&#xD;
  &#xD;
               2. International Standardized ratio (INR) and activated partial thrombin time (APTT)&#xD;
                  ≤1.5× upper limit of normal value (ULN);&#xD;
  &#xD;
               3. Liver function: serum total bilirubin ≤ 1.5 x ULN, ALT/AST ≤ 3 x ULN, serum total&#xD;
                  biliary red ≤ 1.5 x ULN after internal/external drainage for obstructive jaundice;&#xD;
  &#xD;
               4. Renal function: serum creatinine ≤ 1.5 x ULN, creatinine clearance (CCr) ≥&#xD;
                  50mL/min;&#xD;
  &#xD;
               5. Normal cardiac function, left ventricular ejection fraction (LVEF)≥50% by&#xD;
                  two-dimensional echocardiography;&#xD;
  &#xD;
         10. Fertile male or female patients volunteered to use effective contraceptive methods, such&#xD;
             as double screen contraceptives, condoms, oral or injectable contraceptives,&#xD;
             intrauterine devices, etc., during the study period and within 6 months of the last&#xD;
             study medication. All female patients will be considered fertile unless they have&#xD;
             undergone natural menopause, artificial menopause or sterilization.&#xD;
  &#xD;
        Those who met each of the above criteria were included in the study.&#xD;
  &#xD;
        The study proposal shall be excluded if any of the following criteria are met:&#xD;
  &#xD;
          1. Participated in clinical trials of other antitumor drugs within 4 weeks before&#xD;
             enrollment;&#xD;
  &#xD;
          2. Prior treatment with VEGFR inhibitors or prior treatment with immune checkpoint&#xD;
             inhibitors;&#xD;
  &#xD;
          3. Patients with BRCA1/2 germ line mutation;&#xD;
  &#xD;
          4. Patients with obstructive jaundice but failing to reach the expected yellow reduction;&#xD;
  &#xD;
          5. Have had other malignancies within the past 5 years, other than basal cell or squamous&#xD;
             cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;&#xD;
  &#xD;
          6. Patients who have had or currently have any brain metastases;&#xD;
  &#xD;
          7. The investigators determined that liver metastases accounted for 70% or more of the&#xD;
             total liver volume;&#xD;
  &#xD;
          8. Had received any surgery (except biopsy) or invasive treatment or operation within 4&#xD;
             weeks prior to inclusion, and the surgical incision was not completely healed (except&#xD;
             intravenous catheterization, puncture drainage, internal/external drainage for&#xD;
             obstructive jaundice, etc.);&#xD;
  &#xD;
          9. Uncontrolled pleural effusion, pericardial effusion or ascites requiring drainage;&#xD;
  &#xD;
         10. Local antitumor therapy, such as hepatic artery interventional embolization, liver&#xD;
             metastasis cryoablation or radiofrequency ablation, was received within 4 weeks before&#xD;
             enrollment;&#xD;
  &#xD;
         11. Electrolyte abnormalities identified by the investigator as clinically significant;&#xD;
  &#xD;
         12. The patient has medically uncontrolled hypertension, as follows: systolic blood pressure&#xD;
             ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;&#xD;
  &#xD;
         13. Urine routine indicated urinary protein ≥2+ and 24-hour urinary protein volume &amp;gt;&#xD;
             1.0g;&#xD;
  &#xD;
         14. Patients whose tumors are judged to be at high risk of invading vital blood vessels and&#xD;
             causing fatal haemorrhage during the follow-up study;&#xD;
  &#xD;
         15. Patients with significant evidence or history of bleeding tendency within 3 months prior&#xD;
             to enrollment (bleeding within 3 months &amp;gt; 30 mL, hematemesis, black feces, blood in&#xD;
             stool), hemoptysis (within 4 weeks &amp;gt; 5 mL fresh blood); A history of hereditary or&#xD;
             acquired bleeding or a coagulation disorder. Have clinically significant bleeding&#xD;
             symptoms or definite bleeding tendency within 3 months, such as gastrointestinal&#xD;
             bleeding, hemorrhagic gastric ulcer, etc.;&#xD;
  &#xD;
         16. Clinically significant cardiovascular disease, including but not limited to acute&#xD;
             myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within&#xD;
             6 months prior to enrollment; New York Heart Association (NYHA) Grades for Congestive&#xD;
             Heart Failure &amp;gt; Level 2; Ventricular arrhythmias requiring medical treatment;&#xD;
             Electrocardiogram (ECG) showed a QT c interval ≥480 ms;&#xD;
  &#xD;
         17. Active or uncontrolled severe infection (≥CTCAE grade 2 infection);&#xD;
  &#xD;
         18. Unmitigated toxic reactions higher than CTCAE grade 2 or above due to any previous&#xD;
             anticancer therapy, excluding grade 2 or less neurotoxicity due to alopecia,&#xD;
             lymphocytopenia, and oxaliplatin;&#xD;
  &#xD;
         19. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;&#xD;
  &#xD;
         20. Any other medical condition, clinically significant metabolic abnormality, physical&#xD;
             abnormality or laboratory abnormality, which, in the investigator's judgment, the&#xD;
             patient has a medical condition or condition that is reasonably suspected to be&#xD;
             unsuitable for the use of the study drug (such as the presence of epileptic seizures&#xD;
             requiring treatment), or which would interfere with the interpretation of the study&#xD;
             results, or place the patient at high risk;&#xD;
  &#xD;
         21. Known human immunodeficiency virus (HIV) infection; A known history of clinically&#xD;
             significant liver disease, including viral hepatitis [active HBV infection must be ruled&#xD;
             out as a known carrier of hepatitis B virus (HBV), i.e. positive HBV DNA (&amp;gt;1×104&#xD;
             copies /mL or &amp;gt; 2000 IU/ml); known hepatitis C virus infection (HCV) and HCV RNA&#xD;
             positive (&amp;gt;1×103 copies /mL), or other hepatitis, cirrhosis;&#xD;
  &#xD;
         22. The presence of any active, known or suspected autoimmune disease (including but not&#xD;
             limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus&#xD;
             erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis, vasculitis,&#xD;
             glomerulonephritis, uveitis, pituitaritis, hyperthyroidism, etc.);&#xD;
  &#xD;
         23. Allergy or suspected allergy to the study drug or similar drug;&#xD;
  &#xD;
         24. In the investigator's judgment, the patient had other factors that might affect the&#xD;
             study results or lead to the termination of the study, such as alcoholism, drug abuse,&#xD;
             other serious medical conditions (including mental illness) requiring concomitant&#xD;
             treatment, serious laboratory abnormalities, and family or social factors that would&#xD;
             affect the patient's safety.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">July 2025</completion_date>
    <primary_completion_date type="Anticipated">December 2024</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>PFS</measure>
      <time_frame>PFS were defined as from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 16.5 months</time_frame>
      <description>Progression-free survival</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>ORR</measure>
      <time_frame>From date of randomization until the end of treatment or the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 weeks</time_frame>
      <description>objective response rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>OS</measure>
      <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 16.5 months</time_frame>
      <description>Overall survival</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DCR</measure>
      <time_frame>From date of randomization until the end of treatment or the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 weeks</time_frame>
      <description>Disease control rate</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">65</enrollment>
    <condition>Pancreatic Neoplasms</condition>
    <arm_group>
      <arm_group_label>Sofantinib in combination with abraxane and gemcitabine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Abraxane: 125mg/m2 intravenously, d1, 8; Gemcitabine: 1000mg/m2, intravenous infusion greater than 30min, d1, 8, every 3 weeks for a treatment cycle. Sofantinib capsules, 250mg orally, taken within 1 hour after breakfast, once a day for continuous administration, d1-d21, every 3 weeks for a treatment cycle. AG chemotherapy did not exceed a maximum of 6 treatment cycles, and soantinib was continued until disease progression (PD, RECIST 1.1) or death (while the patient was on treatment) or toxicity became intolerant or other criteria for discontinuation of study therapy were met in the protocol. Allow adjustment of dosage according to protocol requirements, including suspension, lowering of dosage or permanent discontinuation.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Abraxane combined with gemcitabine</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Abraxane: 125mg/m2 intravenously, d1, 8; Gemcitabine: 1000mg/m2, intravenous infusion greater than 30min, d1, 8, every 3 weeks as a treatment cycle, treatment until toxicity intolerance or disease progression, death, or other criteria for termination of study therapy as specified in the protocol. AG chemotherapy should not exceed a maximum of 6 treatment cycles. Allow adjustment of dosage according to protocol requirements, including suspension, lowering of dosage or permanent discontinuation.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Sofantinib、abraxane、gemcitabine</intervention_name>
      <description>The combination of 3 weeks was a treatment cycle, and AG chemotherapy was defined as a maximum of 6 treatment cycles, and soantinib was continued until disease progression (PD, RECIST 1.1) or death (during patient treatment) or toxicity intolerance or other criteria for discontinuation of study therapy were met in the protocol.</description>
      <arm_group_label>Sofantinib in combination with abraxane and gemcitabine</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Abraxane combined with gemcitabine</intervention_name>
      <description>Abraxane combined with gemcitabine</description>
      <arm_group_label>Abraxane combined with gemcitabine</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Subjects must meet all of the following criteria for enrollment:&#xD;
  &#xD;
            1. The subjects voluntarily joined the study and signed the informed consent with good&#xD;
               compliance and follow-up;&#xD;
  &#xD;
            2. Unresectable, locally advanced or metastatic pancreatic cancer confirmed by&#xD;
               histopathology or cytology;&#xD;
  &#xD;
            3. Aged between 18 and 75 (including 18 and 75), male or female;&#xD;
  &#xD;
            4. ECOG score: 0-1; Expected survival ≥12 weeks;&#xD;
  &#xD;
            5. Patients who had previously received 2 cycles of AG regimen first-line systemic&#xD;
               therapy for locally advanced or metastatic pancreatic cancer and whose efficacy was&#xD;
               evaluated as CR, PR, SD (excluding SD patients whose efficacy was evaluated as&#xD;
               increased after 2 cycles of therapy);&#xD;
  &#xD;
            6. Patients with postoperative distant metastasis had received adjuvant chemotherapy of&#xD;
               one type and the distance from adjuvant therapy time &amp;gt; Patients with recurrence at&#xD;
               6 months could be included in the group;&#xD;
  &#xD;
            7. At least one measurable lesion (according to RECIST 1.1 criteria); Magnetic resonance&#xD;
               imaging (MRI) enhancement or computed tomography (CT) enhancement accurately measured&#xD;
               the diameter of ≥10mm, conventional CT scan to determine the diameter of at least&#xD;
               20mm.&#xD;
  &#xD;
            8. No serious organic diseases of heart, lung, brain and other organs;&#xD;
  &#xD;
            9. The functions of major organs and bone marrow are basically normal:&#xD;
  &#xD;
                 1. Blood routine: white blood cells ≥ 4.0 x 109/L, neutrophils ≥ 1.5 x 109/L,&#xD;
                    platelets ≥ 80 x 109/L, hemoglobin ≥ 90g/L;&#xD;
  &#xD;
                 2. International Standardized ratio (INR) and activated partial thrombin time (APTT)&#xD;
                    ≤1.5× upper limit of normal value (ULN);&#xD;
  &#xD;
                 3. Liver function: serum total bilirubin ≤ 1.5 x ULN, ALT/AST ≤ 3 x ULN, serum total&#xD;
                    biliary red ≤ 1.5 x ULN after internal/external drainage for obstructive&#xD;
                    jaundice;&#xD;
  &#xD;
                 4. Renal function: serum creatinine ≤ 1.5 x ULN, creatinine clearance (CCr) ≥&#xD;
                    50mL/min;&#xD;
  &#xD;
                 5. Normal cardiac function, left ventricular ejection fraction (LVEF)≥50% by&#xD;
                    two-dimensional echocardiography;&#xD;
  &#xD;
           10. Fertile male or female patients volunteered to use effective contraceptive methods,&#xD;
               such as double screen contraceptives, condoms, oral or injectable contraceptives,&#xD;
               intrauterine devices, etc., during the study period and within 6 months of the last&#xD;
               study medication. All female patients will be considered fertile unless they have&#xD;
               undergone natural menopause, artificial menopause or sterilization.&#xD;
  &#xD;
          Those who met each of the above criteria were included in the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          The study proposal shall be excluded if any of the following criteria are met:&#xD;
  &#xD;
            1. Participated in clinical trials of other antitumor drugs within 4 weeks before&#xD;
               enrollment;&#xD;
  &#xD;
            2. Prior treatment with VEGFR inhibitors or prior treatment with immune checkpoint&#xD;
               inhibitors;&#xD;
  &#xD;
            3. Patients with BRCA1/2 germ line mutation;&#xD;
  &#xD;
            4. Patients with obstructive jaundice but failing to reach the expected yellow reduction;&#xD;
  &#xD;
            5. Have had other malignancies within the past 5 years, other than basal cell or squamous&#xD;
               cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;&#xD;
  &#xD;
            6. Patients who have had or currently have any brain metastases;&#xD;
  &#xD;
            7. The investigators determined that liver metastases accounted for 70% or more of the&#xD;
               total liver volume;&#xD;
  &#xD;
            8. Had received any surgery (except biopsy) or invasive treatment or operation within 4&#xD;
               weeks prior to inclusion, and the surgical incision was not completely healed (except&#xD;
               intravenous catheterization, puncture drainage, internal/external drainage for&#xD;
               obstructive jaundice, etc.);&#xD;
  &#xD;
            9. Uncontrolled pleural effusion, pericardial effusion or ascites requiring drainage;&#xD;
  &#xD;
           10. Local antitumor therapy, such as hepatic artery interventional embolization, liver&#xD;
               metastasis cryoablation or radiofrequency ablation, was received within 4 weeks before&#xD;
               enrollment;&#xD;
  &#xD;
           11. Electrolyte abnormalities identified by the investigator as clinically significant;&#xD;
  &#xD;
           12. The patient has medically uncontrolled hypertension, as follows: systolic blood&#xD;
               pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;&#xD;
  &#xD;
           13. Urine routine indicated urinary protein ≥2+ and 24-hour urinary protein volume &amp;gt;&#xD;
               1.0g;&#xD;
  &#xD;
           14. Patients whose tumors are judged to be at high risk of invading vital blood vessels&#xD;
               and causing fatal haemorrhage during the follow-up study;&#xD;
  &#xD;
           15. Patients with significant evidence or history of bleeding tendency within 3 months&#xD;
               prior to enrollment (bleeding within 3 months &amp;gt; 30 mL, hematemesis, black feces,&#xD;
               blood in stool), hemoptysis (within 4 weeks &amp;gt; 5 mL fresh blood); A history of&#xD;
               hereditary or acquired bleeding or a coagulation disorder. Have clinically significant&#xD;
               bleeding symptoms or definite bleeding tendency within 3 months, such as&#xD;
               gastrointestinal bleeding, hemorrhagic gastric ulcer, etc.;&#xD;
  &#xD;
           16. Clinically significant cardiovascular disease, including but not limited to acute&#xD;
               myocardial infarction, severe/unstable angina, or coronary artery bypass grafting&#xD;
               within 6 months prior to enrollment; New York Heart Association (NYHA) Grades for&#xD;
               Congestive Heart Failure &amp;gt; Level 2; Ventricular arrhythmias requiring medical&#xD;
               treatment; Electrocardiogram (ECG) showed a QT c interval ≥480 ms;&#xD;
  &#xD;
           17. Active or uncontrolled severe infection (≥CTCAE grade 2 infection);&#xD;
  &#xD;
           18. Unmitigated toxic reactions higher than CTCAE grade 2 or above due to any previous&#xD;
               anticancer therapy, excluding grade 2 or less neurotoxicity due to alopecia,&#xD;
               lymphocytopenia, and oxaliplatin;&#xD;
  &#xD;
           19. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;&#xD;
  &#xD;
           20. Any other medical condition, clinically significant metabolic abnormality, physical&#xD;
               abnormality or laboratory abnormality, which, in the investigator's judgment, the&#xD;
               patient has a medical condition or condition that is reasonably suspected to be&#xD;
               unsuitable for the use of the study drug (such as the presence of epileptic seizures&#xD;
               requiring treatment), or which would interfere with the interpretation of the study&#xD;
               results, or place the patient at high risk;&#xD;
  &#xD;
           21. Known human immunodeficiency virus (HIV) infection; A known history of clinically&#xD;
               significant liver disease, including viral hepatitis [active HBV infection must be&#xD;
               ruled out as a known carrier of hepatitis B virus (HBV), i.e. positive HBV DNA&#xD;
               (&amp;gt;1×104 copies /mL or &amp;gt; 2000 IU/ml); known hepatitis C virus infection (HCV) and&#xD;
               HCV RNA positive (&amp;gt;1×103 copies /mL), or other hepatitis, cirrhosis;&#xD;
  &#xD;
           22. The presence of any active, known or suspected autoimmune disease (including but not&#xD;
               limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus&#xD;
               erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis, vasculitis,&#xD;
               glomerulonephritis, uveitis, pituitaritis, hyperthyroidism, etc.);&#xD;
  &#xD;
           23. Allergy or suspected allergy to the study drug or similar drug;&#xD;
  &#xD;
           24. In the investigator's judgment, the patient had other factors that might affect the&#xD;
               study results or lead to the termination of the study, such as alcoholism, drug abuse,&#xD;
               other serious medical conditions (including mental illness) requiring concomitant&#xD;
               treatment, serious laboratory abnormalities, and family or social factors that would&#xD;
               affect the patient's safety.&#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_official>
      <last_name>Jin Xu</last_name>
      <role>Principal Investigator</role>
      <affiliation>180 1731 7267</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jin Xu</last_name>
      <phone>180 1731 7267</phone>
      <email>xujin@fudanpci.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>Fudan University ShangHai Cancer Center</name>
        <address>
          <city>Shanghai</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Jin Xu</last_name>
        <phone>18017317267</phone>
        <email>xujin@fudanpci.org</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 8, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Fudan University</investigator_affiliation>
      <investigator_full_name>Jin Xu</investigator_full_name>
      <investigator_title>Director of Pancreatic Surgery, Affiliated Cancer Hospital of Fudan University</investigator_title>
    </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>Gemcitabine</mesh_term>
      <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
      <mesh_term>Paclitaxel</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05969171
  org study id: IIT-2023-Sufantinib
  nct id: NCT05969171
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a single-center, open-label randomized controlled Phase II clinical study to observe
        and evaluate the efficacy and safety of Sovantinib in combination with AG versus AG
        first-line treatment in patients with locally advanced or metastatic pancreatic cancer.
  
        According to the literature analysis, the mPFS of gemcitabine combined with albumin-binding
        paclitaxel in first-line treatment of metastatic pancreatic cancer was 3.56 months in
        historical controlled studies, and the expected PFS of soantinib combined with AG regimen
        increased from 2.06 months to 4.5 months after 2 cycles of AG regimen. Follow-up time was 12
        months and enrollment time was 18 months. α=0.05 and β=0.2 were used for bilateral test, and
        the PASS 22 software was used for analysis. The sample size of AG group in the control group
        was 29 cases, and that of AG combined with Solvatinib in the experimental group was 29 cases.
        The total sample size needed to be enrolled was 58 cases, and a total of 65 subjects were
        required according to the 10% shedding rate.
  
        This study was divided into three stages: screening period, treatment period and follow-up
        period. During treatment, tumor status was assessed by imaging every 6 weeks (±7 days) until
        disease progression (PD, RECIST 1.1) or death (during patient treatment) or toxicity
        intolerance or other protocol criteria for discontinuation of study therapy were met. A
        maximum of 6 treatment cycles of AG chemotherapy were specified, and soantinib was continued
        until disease progression (PD, RECIST 1.1) or death (during patient treatment) or toxicity
        intolerance or other criteria for discontinuation of study therapy were met in the protocol.
        Tumor treatment and survival status after disease progression were recorded. Safety outcomes
        included AE, changes in laboratory test values, vital signs and electrocardiogram changes.
  This is a single-center, open-label randomized controlled Phase II clinical study to observe
        and evaluate the efficacy and safety of solantinib combined with AG versus AG first-line
        therapy in patients with locally advanced or metastatic pancreatic cancer.
  
        According to the literature analysis, the mPFS of gemcitabine combined with albumin-bound
        paclitaxel in first-line treatment of metastatic pancreatic cancer in historical control
        studies was 3.56 months, and the PFS of solantinib combined with AG regimen was expected to
        increase from 2.06 months to 4.5 months after 2 cycles of AG regimen. Follow-up time was 12
        months and enrollment time was 18 months. α=0.05 and β=0.2 were used for bilateral test, and
        PASS 22 software was used for analysis. The sample size of AG group in the control group was
        29 cases, and that of AG combined with solvatinib in the experimental group was 29 cases. The
        total sample size required to be enrolled was 58 cases, and a total of 65 subjects were
        required according to the calculation of 10% shedding rate.
  
        The study was divided into three stages: screening period, treatment period and follow-up
        period. During treatment, the tumor was evaluated by imaging every 6 weeks (±7 days) until
        disease progression (PD, RECIST 1.1) or death (during the patient's treatment) or toxicity
        became intolerable or other protocol criteria for discontinuation of study therapy were met.
        It is specified that AG chemotherapy should not exceed a maximum of 8 treatment cycles, and
        that solantinib should be continued until disease progression (PD, RECIST 1.1) or death (in
        the course of patient treatment) or toxicity becomes intolerable or other criteria for
        discontinuation of study therapy as specified in the protocol are met. The tumor treatment
        and survival status after disease progression were recorded. Safety outcome measures included
        AE, changes in laboratory test values, vital signs and electrocardiogram changes.
  
        Researchers can add unplanned imaging tests for tumors as clinically necessary.
  
        Subjects must meet all of the following criteria for enrollment:
  
          1. The subjects voluntarily joined the study and signed the informed consent with good
             compliance and follow-up;
  
          2. Unresectable, locally advanced or metastatic pancreatic cancer confirmed by
             histopathology or cytology;
  
          3. Aged between 18 and 75 (including 18 and 75), male or female;
  
          4. ECOG score: 0-1; Expected survival ≥12 weeks;
  
          5. Patients who had previously received 2 cycles of AG regimen first-line systemic therapy
             for locally advanced or metastatic pancreatic cancer and whose efficacy was evaluated as
             CR, PR, SD (excluding SD patients whose efficacy was evaluated as increased after 2
             cycles of therapy);
  
          6. Patients with postoperative distant metastasis had received adjuvant chemotherapy of one
             type and the distance from adjuvant therapy time &gt; Patients with recurrence at 6
             months could be included in the group;
  
          7. At least one measurable lesion (according to RECIST 1.1 criteria); Magnetic resonance
             imaging (MRI) enhancement or computed tomography (CT) enhancement accurately measured
             the diameter of ≥10mm, conventional CT scan to determine the diameter of at least 20mm.
  
          8. No serious organic diseases of heart, lung, brain and other organs;
  
          9. The functions of major organs and bone marrow are basically normal:
  
               1. Blood routine: white blood cells ≥ 4.0 x 109/L, neutrophils ≥ 1.5 x 109/L,
                  platelets ≥ 80 x 109/L, hemoglobin ≥ 90g/L;
  
               2. International Standardized ratio (INR) and activated partial thrombin time (APTT)
                  ≤1.5× upper limit of normal value (ULN);
  
               3. Liver function: serum total bilirubin ≤ 1.5 x ULN, ALT/AST ≤ 3 x ULN, serum total
                  biliary red ≤ 1.5 x ULN after internal/external drainage for obstructive jaundice;
  
               4. Renal function: serum creatinine ≤ 1.5 x ULN, creatinine clearance (CCr) ≥
                  50mL/min;
  
               5. Normal cardiac function, left ventricular ejection fraction (LVEF)≥50% by
                  two-dimensional echocardiography;
  
         10. Fertile male or female patients volunteered to use effective contraceptive methods, such
             as double screen contraceptives, condoms, oral or injectable contraceptives,
             intrauterine devices, etc., during the study period and within 6 months of the last
             study medication. All female patients will be considered fertile unless they have
             undergone natural menopause, artificial menopause or sterilization.
  
        Those who met each of the above criteria were included in the study.
  
        The study proposal shall be excluded if any of the following criteria are met:
  
          1. Participated in clinical trials of other antitumor drugs within 4 weeks before
             enrollment;
  
          2. Prior treatment with VEGFR inhibitors or prior treatment with immune checkpoint
             inhibitors;
  
          3. Patients with BRCA1/2 germ line mutation;
  
          4. Patients with obstructive jaundice but failing to reach the expected yellow reduction;
  
          5. Have had other malignancies within the past 5 years, other than basal cell or squamous
             cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;
  
          6. Patients who have had or currently have any brain metastases;
  
          7. The investigators determined that liver metastases accounted for 70% or more of the
             total liver volume;
  
          8. Had received any surgery (except biopsy) or invasive treatment or operation within 4
             weeks prior to inclusion, and the surgical incision was not completely healed (except
             intravenous catheterization, puncture drainage, internal/external drainage for
             obstructive jaundice, etc.);
  
          9. Uncontrolled pleural effusion, pericardial effusion or ascites requiring drainage;
  
         10. Local antitumor therapy, such as hepatic artery interventional embolization, liver
             metastasis cryoablation or radiofrequency ablation, was received within 4 weeks before
             enrollment;
  
         11. Electrolyte abnormalities identified by the investigator as clinically significant;
  
         12. The patient has medically uncontrolled hypertension, as follows: systolic blood pressure
             ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;
  
         13. Urine routine indicated urinary protein ≥2+ and 24-hour urinary protein volume &gt;
             1.0g;
  
         14. Patients whose tumors are judged to be at high risk of invading vital blood vessels and
             causing fatal haemorrhage during the follow-up study;
  
         15. Patients with significant evidence or history of bleeding tendency within 3 months prior
             to enrollment (bleeding within 3 months &gt; 30 mL, hematemesis, black feces, blood in
             stool), hemoptysis (within 4 weeks &gt; 5 mL fresh blood); A history of hereditary or
             acquired bleeding or a coagulation disorder. Have clinically significant bleeding
             symptoms or definite bleeding tendency within 3 months, such as gastrointestinal
             bleeding, hemorrhagic gastric ulcer, etc.;
  
         16. Clinically significant cardiovascular disease, including but not limited to acute
             myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within
             6 months prior to enrollment; New York Heart Association (NYHA) Grades for Congestive
             Heart Failure &gt; Level 2; Ventricular arrhythmias requiring medical treatment;
             Electrocardiogram (ECG) showed a QT c interval ≥480 ms;
  
         17. Active or uncontrolled severe infection (≥CTCAE grade 2 infection);
  
         18. Unmitigated toxic reactions higher than CTCAE grade 2 or above due to any previous
             anticancer therapy, excluding grade 2 or less neurotoxicity due to alopecia,
             lymphocytopenia, and oxaliplatin;
  
         19. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
  
         20. Any other medical condition, clinically significant metabolic abnormality, physical
             abnormality or laboratory abnormality, which, in the investigator's judgment, the
             patient has a medical condition or condition that is reasonably suspected to be
             unsuitable for the use of the study drug (such as the presence of epileptic seizures
             requiring treatment), or which would interfere with the interpretation of the study
             results, or place the patient at high risk;
  
         21. Known human immunodeficiency virus (HIV) infection; A known history of clinically
             significant liver disease, including viral hepatitis [active HBV infection must be ruled
             out as a known carrier of hepatitis B virus (HBV), i.e. positive HBV DNA (&gt;1×104
             copies /mL or &gt; 2000 IU/ml); known hepatitis C virus infection (HCV) and HCV RNA
             positive (&gt;1×103 copies /mL), or other hepatitis, cirrhosis;
  
         22. The presence of any active, known or suspected autoimmune disease (including but not
             limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
             erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis, vasculitis,
             glomerulonephritis, uveitis, pituitaritis, hyperthyroidism, etc.);
  
         23. Allergy or suspected allergy to the study drug or similar drug;
  
         24. In the investigator's judgment, the patient had other factors that might affect the
             study results or lead to the termination of the study, such as alcoholism, drug abuse,
             other serious medical conditions (including mental illness) requiring concomitant
             treatment, serious laboratory abnormalities, and family or social factors that would
             affect the patient's safety.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: PFS
  time frame: PFS were defined as from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 16.5 months
  description: Progression-free survival
  measure: ORR
  time frame: From date of randomization until the end of treatment or the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 weeks
  description: objective response rate
  measure: OS
  time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 16.5 months
  description: Overall survival
  measure: DCR
  time frame: From date of randomization until the end of treatment or the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 weeks
  description: Disease control rate
  arm group label: Sofantinib in combination with abraxane and gemcitabine
  arm group type: Experimental
  description: Abraxane: 125mg/m2 intravenously, d1, 8; Gemcitabine: 1000mg/m2, intravenous infusion greater than 30min, d1, 8, every 3 weeks for a treatment cycle. Sofantinib capsules, 250mg orally, taken within 1 hour after breakfast, once a day for continuous administration, d1-d21, every 3 weeks for a treatment cycle. AG chemotherapy did not exceed a maximum of 6 treatment cycles, and soantinib was continued until disease progression (PD, RECIST 1.1) or death (while the patient was on treatment) or toxicity became intolerant or other criteria for discontinuation of study therapy were met in the protocol. Allow adjustment of dosage according to protocol requirements, including suspension, lowering of dosage or permanent discontinuation.
  arm group label: Abraxane combined with gemcitabine
  arm group type: Active Comparator
  description: Abraxane: 125mg/m2 intravenously, d1, 8; Gemcitabine: 1000mg/m2, intravenous infusion greater than 30min, d1, 8, every 3 weeks as a treatment cycle, treatment until toxicity intolerance or disease progression, death, or other criteria for termination of study therapy as specified in the protocol. AG chemotherapy should not exceed a maximum of 6 treatment cycles. Allow adjustment of dosage according to protocol requirements, including suspension, lowering of dosage or permanent discontinuation.
  intervention type: Drug
  intervention name: Sofantinib、abraxane、gemcitabine
  description: The combination of 3 weeks was a treatment cycle, and AG chemotherapy was defined as a maximum of 6 treatment cycles, and soantinib was continued until disease progression (PD, RECIST 1.1) or death (during patient treatment) or toxicity intolerance or other criteria for discontinuation of study therapy were met in the protocol.
  arm group label: Sofantinib in combination with abraxane and gemcitabine
  intervention type: Drug
  intervention name: Abraxane combined with gemcitabine
  description: Abraxane combined with gemcitabine
  arm group label: Abraxane combined with gemcitabine
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Jin Xu
  role: Principal Investigator
  affiliation: 180 1731 7267
  last name: Jin Xu
  phone: 180 1731 7267
  email: xujin@fudanpci.org
  facility: 
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Fudan University
  investigator full name: Jin Xu
  investigator title: Director of Pancreatic Surgery, Affiliated Cancer Hospital of Fudan University
  mesh term: Pancreatic Neoplasms
  mesh term: Gemcitabine
  mesh term: Albumin-Bound Paclitaxel
  mesh term: Paclitaxel
  sharing ipd: No