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/NCT05963490</url>
    </required_header>
    <id_info>
      <org_study_id>FDRT-2023-118-3237</org_study_id>
      <nct_id>NCT05963490</nct_id>
    </id_info>
    <brief_title>Regorafenib Alone or in Combination With High/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer</brief_title>
    <acronym>SLOT</acronym>
    <official_title>A Prospective, Randomized, Controlled Phase II Trial of Regorafenib Alone or in Combination With High/Low-dose Radiotherapy Plus Toripalimab as Third-line Treatment in Patients With Metastatic Colorectal 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>
        The study compares the efficacy and safety of regorafenib alone or in combination with&#xD;
        stereotactic ablative radiotherapy (SABR) and low-dose radiotherapy (LDRT) plus toripalimab&#xD;
        in patients with microsatellite stable metastatic colorectal cancer (MSS mCRC). Patients are&#xD;
        randomly assigned (1:1) into the control arm and the experimental arm. Control arm: a total&#xD;
        of 45 patients will receive regorafenib monotherapy. Experimental arm: a total of 45 patients&#xD;
        will first receive 1 cycle of regorafenib and toripalimab followed by SABR/LDRT radiotherapy.&#xD;
        Regorafenib and toripalimab will be continued after the completion of radiotherapy. The&#xD;
        objective response rate (ORR), survival benefits, and adverse effects will be analyzed.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Control arm: regorafenib 120 mg orally once daily on days 1-21 of each 28 days cycle.&#xD;
  &#xD;
        Experimental arm: regorafenib is administered 80 mg once daily on days 1-21 of each 28 days&#xD;
        cycle with intravenous toripalimab 240 mg every 3 weeks. Radiotherapy regimes include 4-8&#xD;
        fractions of 8-12Gy via SABR and up to 1-10Gy at 0.5-2Gy/fraction via LDRT.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 25, 2023</start_date>
    <completion_date type="Anticipated">April 25, 2026</completion_date>
    <primary_completion_date type="Anticipated">April 25, 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>ORR</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>The percentage of patients with objective response in all metastatic lesions. Objective response is defined as complete response (CR) or partial response (PR) per response evaluation criteria (RECIST v1.1) and the immune-related response criteria (iRECIST) after treatment.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>DCR</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>The percentage of patients with disease control in all metastatic lesions. Disease control is defined as CR, PR, or stable disease (SD) per RECIST v1.1 and iRECIST after treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DoR</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>Defined as the time between PR/CR and subsequent progression disease (PD) per RECIST v1.1 and iRECIST or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PFS</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Defined as the time from initiation of treatment to PD or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>OS</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Defined as the time from initiation of treatment to death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>The percentage of patients with treatment-related acute toxicities as assessed by NCI CTCAE v5.0, from treatment initiation until 90 days upon completion of immunotherapy.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">90</enrollment>
    <condition>Microsatellite Stable Metastatic Colorectal Cancer</condition>
    <arm_group>
      <arm_group_label>monotherapy</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>a total of 45 patients will receive regorafenib monotherapy.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>combination therapies</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>a total of 45 patients will first receive 1 cycle of regorafenib and toripalimab followed by SABR/LDRT radiotherapy. Regorafenib and toripalimab will be continued after the completion of radiotherapy.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Regorafenib</intervention_name>
      <description>Regorafenib 120 mg orally once daily on days 1-21 of each 28 days cycle.</description>
      <arm_group_label>monotherapy</arm_group_label>
      <other_name>Stivarga</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Toripalimab</intervention_name>
      <description>240 mg intravenously every 3 weeks</description>
      <arm_group_label>combination therapies</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>High/low-dose radiotherapy</intervention_name>
      <description>4-8 fractions of 8-12Gy via SABR and up to 1-10Gy at 0.5-2Gy/fraction via LDRT.</description>
      <arm_group_label>combination therapies</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Regorafenib</intervention_name>
      <description>Regorafenib 80mg orally once daily on days 1-21 of each 28 days cycle.</description>
      <arm_group_label>combination therapies</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥18 years old&#xD;
  &#xD;
            2. An Eastern Cooperative Oncology Group (ECOG) performance status ≤1&#xD;
  &#xD;
            3. Life expectancy of at least 3 months&#xD;
  &#xD;
            4. Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum&#xD;
  &#xD;
            5. At least two evaluable metastatic lesions for SABR and LDRT according to RECIST 1.1&#xD;
  &#xD;
            6. Progressed on or after the standard first-and second-line therapies or stopped&#xD;
               standard therapy because of unacceptable toxic effects&#xD;
  &#xD;
            7. Previous radiotherapy completed at least 4 weeks before randomization&#xD;
  &#xD;
            8. Adequate bone-marrow, hepatic, and renal function: neutrophils ≥ 1.5 × 10^9/L, Hb ≥ 90&#xD;
               g/L, PLT ≥ 100 × 10^9/L, ALT/ AST≤2.5 ULN, Cr≤1 ULN&#xD;
  &#xD;
            9. Sign the informed consent and have good compliance&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. History of previous treatment with regorafenib and ICIs such as anti-PD-1 or&#xD;
               anti-PD-L1 mAbs&#xD;
  &#xD;
            2. Current severe cardiovascular diseases such as unstable angina, congestive heart&#xD;
               failure, or serious cardiac arrhythmia requiring medication&#xD;
  &#xD;
            3. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before&#xD;
               recruitment&#xD;
  &#xD;
            4. Active autoimmune diseases and immunodeficiencies, known history of organ&#xD;
               transplantation, or systematic use of immunosuppressive agents&#xD;
  &#xD;
            5. Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: HBsAg positive or&#xD;
               HBV DNA positive, anti-HCV antibody testing positive and confirmatory HCV RNA positive&#xD;
  &#xD;
            6. Positive human immunodeficiency virus (HIV) infection, active syphilis infection, or&#xD;
               active pulmonary tuberculosis infection&#xD;
  &#xD;
            7. Severe infections requiring systemic antibiotics, antifungal or antiviral therapy&#xD;
  &#xD;
            8. Uncontrollable pleural effusion, pericardial effusion, or ascites&#xD;
  &#xD;
            9. Other malignancies within 5 years before recruitment, except for non-melanoma skin&#xD;
               cancer, superficial bladder cancer, cervical carcinoma in situ, or breast cancer in&#xD;
               situ that had been effectively treated.&#xD;
  &#xD;
           10. Known history of severe neurological or mental illness such as schizophrenia,&#xD;
               dementia, or epilepsy&#xD;
  &#xD;
           11. Known history of allergy to any component involved in this study.&#xD;
  &#xD;
           12. Pregnancy or breast-feeding women&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Zhen Zhang, MD, PHD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fudan University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Zhen Zhang, MD, PHD</last_name>
      <phone>18801735029</phone>
      <email>zhen_zhang@fudan.edu.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Fudan University Shanghai Cancer Center</name>
        <address>
          <city>Shanghai</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Zhen Zhang, MD, PHD</last_name>
        <phone>18801735029</phone>
        <email>zhen_zhang@fudan.edu.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 19, 2023</study_first_submitted>
    <study_first_submitted_qc>July 19, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>July 19, 2023</last_update_submitted>
    <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 27, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Fudan University</investigator_affiliation>
      <investigator_full_name>Zhen Zhang</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Colorectal Neoplasms</mesh_term>
    </condition_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/NCT05963490
  org study id: FDRT-2023-118-3237
  nct id: NCT05963490
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The study compares the efficacy and safety of regorafenib alone or in combination with
        stereotactic ablative radiotherapy (SABR) and low-dose radiotherapy (LDRT) plus toripalimab
        in patients with microsatellite stable metastatic colorectal cancer (MSS mCRC). Patients are
        randomly assigned (1:1) into the control arm and the experimental arm. Control arm: a total
        of 45 patients will receive regorafenib monotherapy. Experimental arm: a total of 45 patients
        will first receive 1 cycle of regorafenib and toripalimab followed by SABR/LDRT radiotherapy.
        Regorafenib and toripalimab will be continued after the completion of radiotherapy. The
        objective response rate (ORR), survival benefits, and adverse effects will be analyzed.
  Control arm: regorafenib 120 mg orally once daily on days 1-21 of each 28 days cycle.
  
        Experimental arm: regorafenib is administered 80 mg once daily on days 1-21 of each 28 days
        cycle with intravenous toripalimab 240 mg every 3 weeks. Radiotherapy regimes include 4-8
        fractions of 8-12Gy via SABR and up to 1-10Gy at 0.5-2Gy/fraction via LDRT.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: ORR
  time frame: Up to 1 year
  description: The percentage of patients with objective response in all metastatic lesions. Objective response is defined as complete response (CR) or partial response (PR) per response evaluation criteria (RECIST v1.1) and the immune-related response criteria (iRECIST) after treatment.
  measure: DCR
  time frame: Up to 1 year
  description: The percentage of patients with disease control in all metastatic lesions. Disease control is defined as CR, PR, or stable disease (SD) per RECIST v1.1 and iRECIST after treatment.
  measure: DoR
  time frame: Up to 1 year
  description: Defined as the time between PR/CR and subsequent progression disease (PD) per RECIST v1.1 and iRECIST or death from any cause.
  measure: PFS
  time frame: Up to 3 years
  description: Defined as the time from initiation of treatment to PD or death from any cause.
  measure: OS
  time frame: Up to 3 years
  description: Defined as the time from initiation of treatment to death from any cause.
  measure: Adverse events
  time frame: Up to 1 year
  description: The percentage of patients with treatment-related acute toxicities as assessed by NCI CTCAE v5.0, from treatment initiation until 90 days upon completion of immunotherapy.
  arm group label: monotherapy
  arm group type: Active Comparator
  description: a total of 45 patients will receive regorafenib monotherapy.
  arm group label: combination therapies
  arm group type: Experimental
  description: a total of 45 patients will first receive 1 cycle of regorafenib and toripalimab followed by SABR/LDRT radiotherapy. Regorafenib and toripalimab will be continued after the completion of radiotherapy.
  intervention type: Drug
  intervention name: Regorafenib
  description: Regorafenib 120 mg orally once daily on days 1-21 of each 28 days cycle.
  arm group label: monotherapy
  other name: Stivarga
  intervention type: Drug
  intervention name: Toripalimab
  description: 240 mg intravenously every 3 weeks
  arm group label: combination therapies
  intervention type: Radiation
  intervention name: High/low-dose radiotherapy
  description: 4-8 fractions of 8-12Gy via SABR and up to 1-10Gy at 0.5-2Gy/fraction via LDRT.
  arm group label: combination therapies
  intervention type: Drug
  intervention name: Regorafenib
  description: Regorafenib 80mg orally once daily on days 1-21 of each 28 days cycle.
  arm group label: combination therapies
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Zhen Zhang, MD, PHD
  role: Principal Investigator
  affiliation: Fudan University
  last name: Zhen Zhang, MD, PHD
  phone: 18801735029
  email: zhen_zhang@fudan.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Fudan University
  investigator full name: Zhen Zhang
  investigator title: Professor
  mesh term: Colorectal Neoplasms