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/NCT06018714</url>
    </required_header>
    <id_info>
      <org_study_id>2023-FXY-096-Department of CRC</org_study_id>
      <nct_id>NCT06018714</nct_id>
    </id_info>
    <brief_title>Efficacy of Modified Fruquintinib in Colorectal Cancer Liver Metastases: A Phase II Study</brief_title>
    <official_title>The Clinical Efficacy of Modified Fruquintinib as Maintenance Treatment for Colorectal Cancer Liver Metastases After NED: Phase II Single-arm Prospective Study</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>
      <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>
        The overall 5-year survival rate for patients with colorectal liver metastases (CRLM) is&#xD;
        still less than 20%. Surgery-based local treatment can achieve no evidence of disease (NED)&#xD;
        in CRLM patients, but over 60% of patients experience recurrence even after achieving NED.&#xD;
        Even with adjuvant therapy for the 6-month perioperative period after achieving NED, the&#xD;
        recurrence rate remains high. Fruquintinib is a selective anti-angiogenic inhibitor that may&#xD;
        help reduce tumor recurrence and prolong the time to recurrence and metastasis. The Chinese&#xD;
        Society of Clinical Oncology (CSCO) guidelines have recommended fruquintinib as a third-line&#xD;
        therapy for colorectal cancer. This study aims to evaluate the effectiveness and safety of&#xD;
        fruquintinib as a maintenance therapy for patients with advanced colorectal cancer (CRC) who&#xD;
        have achieved no evidence of disease (NED) after completing adjuvant chemotherapy.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 1, 2023</start_date>
    <completion_date type="Anticipated">August 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 1, 2024</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>
      <intervention_model_description>This is a prospective, single-arm, phase II study aimed at exploring the clinical efficacy and safety of fruquintinib as maintenance therapy for advanced CRC patients who achieve NED after adjuvant chemotherapy. Patients will receive full supportive care while on this study.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>2-year recurrence and metastasis rate</measure>
      <time_frame>2 years after NED</time_frame>
      <description>To evaluate the clinical efficacy and safety of fruquintinib as maintenance therapy for advanced CRC patients who achieve NED after adjuvant chemotherapy, with the 2-year recurrence and metastasis rate as the primary indicator.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>2-year disease-free survival rate</measure>
      <time_frame>2 years after NED</time_frame>
      <description>To evaluate 2-year recurrence-free survival rate, 2-year overall survival rate, recurrence-free survival period in patients accepting fruquintinib maintenance therapy.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>completion rate of maintenance therapy</measure>
      <time_frame>2 years after NED</time_frame>
      <description>To evaluate safety and completion rate of maintenance therapy</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">64</enrollment>
    <condition>Colorectal Cancer Metastatic</condition>
    <arm_group>
      <arm_group_label>Fruquintinib group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients will receive Fruquintinib maintenance treatment for six months, or until tumor recurrence, metastasis, or intolerable drug toxicities occur within six months.&#xD;
  After achieving no evidence of disease (NED), a chest, abdomen, and pelvic CT scan with contrast or a chest CT scan with abdominal and pelvic MRI scan will be performed every 6 months within 2 years. Colonoscopy will be performed annually. CEA, CA19-9, and abdominal and pelvic ultrasound will be performed every 3 months. If abnormalities are found, further imaging studies and colonoscopy will be conducted, and if necessary, a PET/CT scan will be performed.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fruquintinib</intervention_name>
      <description>Drug:&#xD;
  Maintenance treatment regimen:&#xD;
  Fruquintinib 5 mg, qd, po, with three weeks of continuous treatment followed by one week of drug discontinuation. Each treatment cycle lasts four weeks. The treatment will be continued for six months, or until tumor recurrence, metastasis, or intolerable drug toxicities occur within six months.&#xD;
  Adverse drug reactions that occur during the trial will be graded according to the NCI CTCAE version 5.0 and dose adjustments will be made according to the corresponding rules.</description>
      <arm_group_label>Fruquintinib group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. . The pathological diagnosis was colorectal adenocarcinoma liver metastasis；&#xD;
  &#xD;
            2. . Age: 18 to 75 years old,allgenders；&#xD;
  &#xD;
            3. . Patients who have previously received first-line chemotherapy and have achieved&#xD;
               disease control (PR+SD) according to RECIST 1.1;&#xD;
  &#xD;
            4. . Patients with liver metastasis of colorectal cancer who have undergone curative&#xD;
               local treatment (surgery, ablation, SBRT) and achieved no evidence of disease (NED).&#xD;
               Definition of NED: a. After local treatment, no residual signs of primary or&#xD;
               metastatic tumors are observed on CT, MRI, PET-CT imaging, or b. No cancer cells are&#xD;
               found in biopsies of suspicious lesions；&#xD;
  &#xD;
            5. .Completed adjuvant chemotherapy after achieving NED (e.g. 4-8 cycles of CapOX&#xD;
               regimen, 6-12 cycles of FOLFOX regimen, or without receiving adjuvant chemotherapy&#xD;
               recently) and evaluated as no disease progression. Last chemotherapy within 2 months&#xD;
               from enrollment.&#xD;
  &#xD;
            6. . The time interval between the last chemotherapy and enrollment does not exceed 2&#xD;
               months;&#xD;
  &#xD;
            7. . Performance status (ECOG score) ≤ 2&#xD;
  &#xD;
            8. . Hematology: WBC &gt; 3 × 10^9 / L; PLT &gt; 80 × 10^9 / L; Hb &gt; 90 g/L;&#xD;
  &#xD;
            9. . Liver function: ALT and AST ≤ 2.5 × ULN; bilirubin ≤ 1.5 × ULN;&#xD;
  &#xD;
           10. .Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCr) ≥ 60&#xD;
               ml/min;&#xD;
  &#xD;
           11. .Signed informed consent, willingness to undergo treatment according to this protocol,&#xD;
               and good compliance with medication.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. .Patients with tumor progression before enrollment following the completion of&#xD;
               chemotherapy.&#xD;
  &#xD;
            2. .Intestinal obstruction or incomplete intestinal obstruction.&#xD;
  &#xD;
            3. .Co-existing with other serious illnesses, including severe electrolyte disorders,&#xD;
               bleeding tendencies, etc.&#xD;
  &#xD;
            4. .Active or uncontrolled severe infections: a) Known human immunodeficiency virus (HIV)&#xD;
               infection. b) Known clinically significant liver disease history, including viral&#xD;
               hepatitis [known carriers of hepatitis B virus (HBV) must exclude active HBV&#xD;
               infection, i.e., HBV DNA positive (&gt;1×104 copies/mL or &gt;2000 IU/mL)]. c) Known&#xD;
               hepatitis C virus (HCV) infection with positive HCV RNA (&gt;1×103 copies/mL), or other&#xD;
               hepatitis, liver cirrhosis.&#xD;
  &#xD;
            5. .Women who are pregnant or breastfeeding and have childbearing potential but are not&#xD;
               taking adequate contraceptive measures.&#xD;
  &#xD;
            6. .Patients with severe brain disorders or mental illnesses (such as depression, mania,&#xD;
               obsessive-compulsive disorder, and schizophrenia) that affect the patient's ability to&#xD;
               self-report.&#xD;
  &#xD;
            7. .Patients with autoimmune diseases, blood system disorders, and a history of organ&#xD;
               transplantation, long-term use of steroids, or immunosuppressive agents.&#xD;
  &#xD;
            8. .History of other malignant tumors within the past 5 years, excluding cured cervical&#xD;
               carcinoma in situ or basal cell carcinoma of the skin.&#xD;
  &#xD;
            9. .History of organ transplantation (including autologous bone marrow transplantation&#xD;
               and peripheral stem cell transplantation).&#xD;
  &#xD;
           10. .Known or suspected allergies to the investigational drug fruquintinib.&#xD;
  &#xD;
           11. .Hypertension that cannot be well controlled with antihypertensive medications&#xD;
               (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).&#xD;
  &#xD;
           12. .Active cardiac disease within 6 months prior to treatment, including myocardial&#xD;
               infarction, severe/unstable angina pectoris. Left ventricular ejection fraction &lt;50%&#xD;
               on echocardiography, poorly controlled arrhythmias.&#xD;
  &#xD;
           13. .Urinalysis indicating urine protein ≥2+ and 24-hour urine protein quantification&#xD;
               &gt;1.0g.&#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>Junzhong Lin, Doctor</last_name>
      <phone>020-87343533</phone>
      <email>linjzh@sysucc.org.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Zhizhong Pan, Prof</last_name>
      <phone>020-87343533</phone>
      <email>panzhzh@sysucc.org.cn</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Colorectal Department,SunYat-sen University Cancer Center</name>
        <address>
          <city>Guangzhou</city>
          <state>Guangdong</state>
          <zip>510062</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Junzhong lin, PhD</last_name>
        <phone>+86-13802446666</phone>
        <email>linjzh@sysucc.org.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 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>ZHI-ZHONG PAN</investigator_full_name>
      <investigator_title>Prof.</investigator_title>
    </responsible_party>
    <keyword>Colorectal cancer</keyword>
    <keyword>Fruquintinib</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Colorectal 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>
  
  
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/NCT06018714
  org study id: 2023-FXY-096-Department of CRC
  nct id: NCT06018714
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The overall 5-year survival rate for patients with colorectal liver metastases (CRLM) is
        still less than 20%. Surgery-based local treatment can achieve no evidence of disease (NED)
        in CRLM patients, but over 60% of patients experience recurrence even after achieving NED.
        Even with adjuvant therapy for the 6-month perioperative period after achieving NED, the
        recurrence rate remains high. Fruquintinib is a selective anti-angiogenic inhibitor that may
        help reduce tumor recurrence and prolong the time to recurrence and metastasis. The Chinese
        Society of Clinical Oncology (CSCO) guidelines have recommended fruquintinib as a third-line
        therapy for colorectal cancer. This study aims to evaluate the effectiveness and safety of
        fruquintinib as a maintenance therapy for patients with advanced colorectal cancer (CRC) who
        have achieved no evidence of disease (NED) after completing adjuvant chemotherapy.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: This is a prospective, single-arm, phase II study aimed at exploring the clinical efficacy and safety of fruquintinib as maintenance therapy for advanced CRC patients who achieve NED after adjuvant chemotherapy. Patients will receive full supportive care while on this study.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 2-year recurrence and metastasis rate
  time frame: 2 years after NED
  description: To evaluate the clinical efficacy and safety of fruquintinib as maintenance therapy for advanced CRC patients who achieve NED after adjuvant chemotherapy, with the 2-year recurrence and metastasis rate as the primary indicator.
  measure: 2-year disease-free survival rate
  time frame: 2 years after NED
  description: To evaluate 2-year recurrence-free survival rate, 2-year overall survival rate, recurrence-free survival period in patients accepting fruquintinib maintenance therapy.
  measure: completion rate of maintenance therapy
  time frame: 2 years after NED
  description: To evaluate safety and completion rate of maintenance therapy
  arm group label: Fruquintinib group
  arm group type: Experimental
  description: Patients will receive Fruquintinib maintenance treatment for six months, or until tumor recurrence, metastasis, or intolerable drug toxicities occur within six months.
  After achieving no evidence of disease (NED), a chest, abdomen, and pelvic CT scan with contrast or a chest CT scan with abdominal and pelvic MRI scan will be performed every 6 months within 2 years. Colonoscopy will be performed annually. CEA, CA19-9, and abdominal and pelvic ultrasound will be performed every 3 months. If abnormalities are found, further imaging studies and colonoscopy will be conducted, and if necessary, a PET/CT scan will be performed.
  intervention type: Drug
  intervention name: Fruquintinib
  description: Drug:
  Maintenance treatment regimen:
  Fruquintinib 5 mg, qd, po, with three weeks of continuous treatment followed by one week of drug discontinuation. Each treatment cycle lasts four weeks. The treatment will be continued for six months, or until tumor recurrence, metastasis, or intolerable drug toxicities occur within six months.
  Adverse drug reactions that occur during the trial will be graded according to the NCI CTCAE version 5.0 and dose adjustments will be made according to the corresponding rules.
  arm group label: Fruquintinib group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Junzhong Lin, Doctor
  phone: 020-87343533
  email: linjzh@sysucc.org.cn
  last name: Zhizhong Pan, Prof
  phone: 020-87343533
  email: panzhzh@sysucc.org.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Sun Yat-sen University
  investigator full name: ZHI-ZHONG PAN
  investigator title: Prof.
  mesh term: Colorectal Neoplasms
  sharing ipd: No