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/NCT05993702</url>
    </required_header>
    <id_info>
      <org_study_id>PRAY</org_study_id>
      <nct_id>NCT05993702</nct_id>
    </id_info>
    <brief_title>TAS-102 in Combination With Regorafenib or Fruquintinib for Third-line and Above Advanced Colorectal Cancer</brief_title>
    <official_title>Single-arm, Multicentre Real-world Observational Study of TAS-102 in Combination With Regorafenib or Fruquintinib for Third-line and Above Advanced Colorectal Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>China Medical University, China</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>China Medical University, China</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a single-arm, multicentre real-world observational study of TAS-102 in combination&#xD;
        with regorafenib or fruquintinib for third-line and above advanced colorectal cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a single-arm, multicentre real-world observational study of TAS-102 in combination&#xD;
        with regorafenib or fruquintinib for third-line and above advanced colorectal cancer.The&#xD;
        purpose of the study is to evaluate the efficacy and safety of TAS-102 in combination with a&#xD;
        regimen of regorafenib or fruquintinib for the treatment of advanced colorectal cancer in the&#xD;
        third line and above.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">June 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">June 1, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Progression-free Survival (PFS)</measure>
      <time_frame>one year</time_frame>
      <description>PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR)</measure>
      <time_frame>one year</time_frame>
      <description>ORR, determined using RECIST v1.1, defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR)</measure>
      <time_frame>one year</time_frame>
      <description>Determined using RECIST v1.1 criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence and severity of adverse events (AE) and serious adverse events (SAE)</measure>
      <time_frame>two years</time_frame>
      <description>Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0.</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">45</enrollment>
    <condition>TAS 102</condition>
    <condition>Regorafenib</condition>
    <condition>Fruquintinib</condition>
    <condition>Gastrointestinal Tumours</condition>
    <arm_group>
      <arm_group_label>TAS-102 in combination with regorafenib</arm_group_label>
      <description>(TAS102): Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; (TKI: regorafenib: regorafenib capsules administered at a dose of 80 mg (2 tablets, each containing 40 mg regorafenib) once daily for a 28-day cycle)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>TAS-102 in combination with fruquintinib</arm_group_label>
      <description>TAS102: Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; Fruquintinib: a dose of 3mg/dose administered orally once daily, continuously for 28 days as a cycle.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>regorafenib</intervention_name>
      <description>(TAS102): Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; (TKI: regorafenib: regorafenib capsules administered at a dose of 80 mg (2 tablets, each containing 40 mg regorafenib) once daily for a 28-day cycle)</description>
      <arm_group_label>TAS-102 in combination with regorafenib</arm_group_label>
      <other_name>baiwange</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>fruquintinib</intervention_name>
      <description>TAS102: Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; or Fruquintinib: a dose of 3mg/dose administered orally once daily, continuously for 28 days as a cycle.</description>
      <arm_group_label>TAS-102 in combination with fruquintinib</arm_group_label>
      <other_name>elunate</other_name>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Male or female patients between the ages of 18-75 years&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male or female patients between the ages of 18-75 years;&#xD;
  &#xD;
            2. Patients with colorectal cancer diagnosed by histology or cytology;&#xD;
  &#xD;
            3. Patients with metastatic colorectal cancer who have failed two or more standard&#xD;
               therapies; patients are permitted to have received prior chemotherapy with&#xD;
               fluorouracil, oxaliplatin, irinotecan, and other regimens, patients are permitted to&#xD;
               receive EGFR and/or VEGF inhibitors, and patients are permitted to have received prior&#xD;
               immunotherapy;&#xD;
  &#xD;
            4. Have at least one measurable lesion according to the solid tumour efficacy evaluation&#xD;
               criteria RECIST version 1.1; the measurable lesion should not have received local&#xD;
               treatment such as radiotherapy (lesions located within the area of previous&#xD;
               radiotherapy may also be selected as target lesions if progression is confirmed to&#xD;
               have occurred and meets the RECIST 1.1 criteria);&#xD;
  &#xD;
            5. ECOG PS score: 0 to 1; expected survival more than 3 months;&#xD;
  &#xD;
            6. Oral medication is available;&#xD;
  &#xD;
            7. have adequate organ and bone marrow function, i.e., meet the following criteria:&#xD;
  &#xD;
          (1) Criteria for routine blood tests need to be met: Haemoglobin level (HB) ≥ 90 g/L (no&#xD;
          transfusion within 28 days); Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Platelet count&#xD;
          (PLT) ≥ 100×109/L. (2) Biochemical tests need to meet the following criteria: Serum total&#xD;
          bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN) ; ALT and AST ≤ 2.5 ULN (ALT&#xD;
          and AST ≤ 5 ULN if liver metastases are present); Cr ≤ 1.5 ULN or creatinine clearance&#xD;
          (CCr) ≥ 60 ml/min; (Cockcroft-Gault formula) (3) Adequate coagulation function, defined as&#xD;
          International Normalised Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times ULN; 8) Pregnant&#xD;
          or breastfeeding patients: 1) Females and males of childbearing potential must agree to use&#xD;
          adequate contraception prior to entering the programme until at least 8 weeks after the&#xD;
          last dose of study drug. The Investigator or designee is required to advise subjects on how&#xD;
          to achieve adequate contraception. Appropriate contraception is defined in the study as any&#xD;
          medically recommended method (or combination of methods) based on standard treatment 2)&#xD;
          Women of childbearing age must have a negative serum or urine pregnancy test confirmed&#xD;
          within 7 days prior to initiating treatment and must agree to record a negative result&#xD;
          prior to entering the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          - study:&#xD;
  &#xD;
            1. Patients with abnormal coagulation or a tendency to gastrointestinal bleeding on&#xD;
               thrombolytic or anticoagulant medication, including active peptic ulcers with fecal&#xD;
               occult blood++, vomiting blood or black stools within 3 months.&#xD;
  &#xD;
            2. Prior or concurrent cancers with a primary site or histology different from CRC within&#xD;
               the year of enrolment, with the exception of cured in situ cervical cancer,&#xD;
               non-melanoma skin cancers, and superficial bladder tumours:staging Ta, Tis and T1 .&#xD;
  &#xD;
            3. Arterial or venous thrombotic or embolic events, such as cerebrovascular accidents&#xD;
               (including transient ischaemic attacks), deep vein thrombosis, or pulmonary embolism&#xD;
               (except for appropriately treated catheter-associated venous thrombosis occurring more&#xD;
               than 1 month after initiation of therapy), have occurred within 6 months prior to the&#xD;
               start of treatment.&#xD;
  &#xD;
            4. Major surgery, biopsy or significant traumatic injury within 28 days prior to the&#xD;
               start of investigational therapy.&#xD;
  &#xD;
            5. Unhealed wounds, ulcers, or fractures.&#xD;
  &#xD;
            6. Patients with brain metastases and/or carcinomatous meningitis.&#xD;
  &#xD;
            7. Congestive heart failure &gt;New York Heart Association (NYHA) class 2.&#xD;
  &#xD;
            8. Unstable angina (angina at rest), new onset angina (within the last 3 months).&#xD;
               Myocardial infarction within 6 months prior to the start of treatment.&#xD;
  &#xD;
            9. Arrhythmia requiring antiarrhythmic therapy (beta-blockers or digoxin permitted).&#xD;
               Uncontrolled hypertension. (Systolic blood pressure &gt; 150 mmHg or diastolic blood&#xD;
               pressure &gt; 90 mmHg despite optimal medical therapy).&#xD;
  &#xD;
           10. Patients with pheochromocytoma&#xD;
  &#xD;
           11. Pleural effusion or ascites causing respiratory restriction (≥ CTCAE grade 2 dyspnoea)&#xD;
  &#xD;
           12. Active infection &gt;NCI CTCAE2 level&#xD;
  &#xD;
           13. interstitial lung disease with signs and symptoms at the time of informed consent&#xD;
  &#xD;
           14. known hypersensitivity to any of the drugs in the study, to drugs of the same class as&#xD;
               the study drug, or to excipients in dosage forms&#xD;
  &#xD;
           15. use of CYP3A4 inhibitors or inducers&#xD;
  &#xD;
           16. Participation in another clinical trial within 4 weeks prior to enrolment and receipt&#xD;
               of the investigational drug and any concomitant therapy containing the investigational&#xD;
               drug&#xD;
  &#xD;
           17. have received radiotherapy within 4 weeks prior to enrolment and the lesion under&#xD;
               observation in this study is in the target area of radiotherapy&#xD;
  &#xD;
           18. Subjects with active tuberculosis (TB) who are receiving anti-tuberculosis treatment&#xD;
               or have received anti-tuberculosis treatment within one year prior to screening&#xD;
  &#xD;
           19. Subjects with comorbidities requiring long-term treatment with immunosuppressive drugs&#xD;
               or systemic or topical corticosteroids at immunosuppressive doses (&gt;10mg/day of&#xD;
               prednisone or other equipotent hormones).&#xD;
  &#xD;
           20. Received any anti-infective vaccine (e.g., influenza vaccine, varicella vaccine,&#xD;
               neocoronavirus vaccine, etc.) within 4 weeks prior to enrolment.&#xD;
  &#xD;
           21. Pregnancy or breastfeeding&#xD;
  &#xD;
           22. Persistent proteinuria &gt;3.5 g/24 hours by measurement of urine protein-creatinine&#xD;
               ratio (grade 3, NCI-CTCAE version 5.0) in random urine samples.&#xD;
  &#xD;
           23. Human immunodeficiency virus (HIV) positive&#xD;
  &#xD;
           24. Hepatitis B virus surface antigen (HBsAg) positive and HBV DNA copy number positive&#xD;
               (quantitative test ≥1000 cps/ml)&#xD;
  &#xD;
           25. Positive blood test for chronic hepatitis C (HCV antibody positive)&#xD;
  &#xD;
           26. renal failure requiring haemodialysis or peritoneal dialysis&#xD;
  &#xD;
           27. Dehydration ≥ CTCAE Version 5.0 Level 1&#xD;
  &#xD;
           28. Persons who are legally incompetent.&#xD;
  &#xD;
           29. Any other clinically significant disease or condition that, in the opinion of the&#xD;
               investigator, may affect adherence to the protocol, or the signing of the Informed&#xD;
               Consent Form (ICF) by the subject, or make participation in this clinical trial&#xD;
               inappropriate.&#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>Yunpeng Liu, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>First Hospital of China Medical University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Yunpeng Liu, PhD</last_name>
      <phone>86-24-83282312</phone>
      <email>cmu_trial@163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Ling Xu, PhD</last_name>
      <email>cmuxuling@163.com</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>China Medical University, China</investigator_affiliation>
      <investigator_full_name>Yunpeng Liu</investigator_full_name>
      <investigator_title>Director of Department of Medical Oncology</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Digestive System Neoplasms</mesh_term>
      <mesh_term>Gastrointestinal 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/NCT05993702
  org study id: PRAY
  nct id: NCT05993702
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a single-arm, multicentre real-world observational study of TAS-102 in combination
        with regorafenib or fruquintinib for third-line and above advanced colorectal cancer.
  This is a single-arm, multicentre real-world observational study of TAS-102 in combination
        with regorafenib or fruquintinib for third-line and above advanced colorectal cancer.The
        purpose of the study is to evaluate the efficacy and safety of TAS-102 in combination with a
        regimen of regorafenib or fruquintinib for the treatment of advanced colorectal cancer in the
        third line and above.
  observational model: Cohort
  time perspective: Prospective
  measure: Progression-free Survival (PFS)
  time frame: one year
  description: PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first.
  measure: Objective Response Rate (ORR)
  time frame: one year
  description: ORR, determined using RECIST v1.1, defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.
  measure: Disease Control Rate (DCR)
  time frame: one year
  description: Determined using RECIST v1.1 criteria.
  measure: Incidence and severity of adverse events (AE) and serious adverse events (SAE)
  time frame: two years
  description: Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0.
  arm group label: TAS-102 in combination with regorafenib
  description: (TAS102): Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; (TKI: regorafenib: regorafenib capsules administered at a dose of 80 mg (2 tablets, each containing 40 mg regorafenib) once daily for a 28-day cycle)
  arm group label: TAS-102 in combination with fruquintinib
  description: TAS102: Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; Fruquintinib: a dose of 3mg/dose administered orally once daily, continuously for 28 days as a cycle.
  intervention type: Drug
  intervention name: regorafenib
  description: (TAS102): Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; (TKI: regorafenib: regorafenib capsules administered at a dose of 80 mg (2 tablets, each containing 40 mg regorafenib) once daily for a 28-day cycle)
  arm group label: TAS-102 in combination with regorafenib
  other name: baiwange
  intervention type: Drug
  intervention name: fruquintinib
  description: TAS102: Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; or Fruquintinib: a dose of 3mg/dose administered orally once daily, continuously for 28 days as a cycle.
  arm group label: TAS-102 in combination with fruquintinib
  other name: elunate
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Yunpeng Liu, PhD
  role: Principal Investigator
  affiliation: First Hospital of China Medical University
  last name: Yunpeng Liu, PhD
  phone: 86-24-83282312
  email: cmu_trial@163.com
  last name: Ling Xu, PhD
  email: cmuxuling@163.com
  responsible party type: Principal Investigator
  investigator affiliation: China Medical University, China
  investigator full name: Yunpeng Liu
  investigator title: Director of Department of Medical Oncology
  mesh term: Digestive System Neoplasms
  mesh term: Gastrointestinal Neoplasms
  sharing ipd: No