<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/NCT04462965</url>
  </required_header>
  <id_info>
    <org_study_id>JS001-ISS-CO148</org_study_id>
    <nct_id>NCT04462965</nct_id>
  </id_info>
  <brief_title>Postoperative Adjuvant Treatment of Completely Resected Mucosal Melanoma Phase II Study</brief_title>
  <official_title>A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Study to Evaluate the Efficacy and Safety of Toripalimab Combined With Temozolomide and Cisplatin in the Postoperative Adjuvant Treatment of Completely Resected Mucosal Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University Cancer Hospital &amp; Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking University Cancer Hospital &amp; Institute</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>
      A mucosal melanoma postoperative adjuvant treatment of multicenter, randomized, double-blind,&#xD;
      placebo-controlled phase II study, evaluation of mucosal melanoma patients accept completely&#xD;
      resected, Toripalima Combined with Temozolomide and Cisplatin postoperative adjuvant therapy&#xD;
      efficacy and safety&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 30, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">November 30, 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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>RFS assessment per RECIST 1.1.</measure>
    <time_frame>2 years</time_frame>
    <description>To Compare the recurrence free survival (RFS) per response evaluation crieria in solid tumors(RECIST 1.1) in subjects of the postoperative adjuvant treatment of completely resected mucosal melanoma treated between Toripalima combined with Temozolomide and Cisplatin and placebo combined with Temozolomideand Cisplatin .</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>RFS assessment per RECIST1.1 in 1 year and 2 year;</measure>
    <time_frame>2 years</time_frame>
    <description>1 year and 2 year recurrence free survival rate of completely resected mucosal melanoma with postoperative adjuvant treatment, will be assessed using RECIST1.1 to evaluate tumor recurrence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DMFS assessed by investigator per RECIT1.1;</measure>
    <time_frame>2 years</time_frame>
    <description>Distant metastasis free survival (DMFS) of completely resected mucosal melanoma with postoperative adjuvant treatment per RECIST 1.1;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) per death time;</measure>
    <time_frame>2 years</time_frame>
    <description>Overall survival (OS) of completely resected mucosal melanoma with postoperative adjuvant treatment per death time;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>.Incidence and grade of AEs and SAEs related to study drugs per NCI-CTCAE version 5.0, AEs ≥ grade 3 related to the study drugs.</measure>
    <time_frame>2 years</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 for safty evaluation.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">294</enrollment>
  <condition>Mucosal Melanoma</condition>
  <arm_group>
    <arm_group_label>Test group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Toripalima Combined with Temozolomide and Cisplatin. Toripalima3 mg/kg intravenous infusion, administered once every 2 weeks (1 treatment cycle every 2 weeks) for a maximum of 1 year. Temozolomide, Oral 200mg/m2 1-5 days and Cisplatin, Iv infusion 25 mg/m2/d for a period of 1 to 3 days, 28 days for 1 cycle, lasting 6 cycles;</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Combined with Temozolomide and Cisplatin. Toripalima3 mg/kg intravenous infusion, administered once every 2 weeks (1 treatment cycle every 2 weeks) for a maximum of 1 year. Temozolomide, Oral 200mg/m2 1-5 days and Cisplatin, Iv infusion 25 mg/m2/d for a period of 1 to 3 days, 28 days for 1 cycle, lasting 6 cycles;</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Toripalimab</intervention_name>
    <description>Injection,Specification 240mg/6ml, 3 mg/kg for the dose, iV, every 2 weeks a dose cycle, up to 1 year; Temozolomide: 100mg or 20mg, Every 4 weeks a dose cycle, up to 6 cycles Cisplatin: Injection, 20mg,Every 4 weeks a dose cycle, up to 6 cycles</description>
    <arm_group_label>Test group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>Placebo：Injection,Specification 240mg/6ml, 3 mg/kg for the dose, iV, every 2 weeks a dose cycle, up to 1 year; Temozolomide: 100mg or 20mg, Every 4 weeks a dose cycle, up to 6 cycles Cisplatin: Injection, 20mg,Every 4 weeks a dose cycle, up to 6 cycles</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-75 years, male or female；&#xD;
&#xD;
          2. Histopathologically confirmed and diagnosed as mucosal melanoma;&#xD;
&#xD;
          3. ECOG score 0 or 1;&#xD;
&#xD;
          4. The primary lesion is completely resected and the surgical margin is (-); Complete&#xD;
             whole-body staging examination (including: brain enhanced CT or MRI, chest, abdomen,&#xD;
             pelvic enhanced CT (nasopharyngeal MRI or CT, oropharyngeal MRI or CT), superficial&#xD;
             lymph node b-ultrasound; or whole body PET-CT) should be performed before enrollment&#xD;
             to confirm there are no regional or distant metastases (patients with contrast media&#xD;
             allergy may choose plain CT);&#xD;
&#xD;
          5. The patient is not receiving standard adjuvant treatment；&#xD;
&#xD;
          6. No contraindications, having adequate organ and marrow function；&#xD;
&#xD;
          7. Use of highly-effective contraceptive methods during the whole study for men of&#xD;
             reproduction ability or women of childbearing potential (e.g. oral contraceptives,&#xD;
             intrauterine contraceptive device, abstinence of sexual intercourse or barrier&#xD;
             contraception in combination with spermatocide), and continuation of contraception for&#xD;
             12 months after the end of treatment；&#xD;
&#xD;
          8. Enrolled for treatment within 4 months post-procedure;&#xD;
&#xD;
          9. The subject is voluntary to participate in the study, sign the informed consent form,&#xD;
             with good compliance and willingness to cooperate with follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previously treated with anti-PD-1, anti-PD-L1, anti-PD-L2;&#xD;
&#xD;
          2. Known allergy to recombinant humanized anti-PD-1 monoclonal antibody drug and its&#xD;
             components;&#xD;
&#xD;
          3. High dose of interferon therapy or adjuvant chemotherapy (Temozolomide + Cisplatin)&#xD;
             was performed after surgery;&#xD;
&#xD;
          4. Skin melanoma, eye melanoma(except the conjunctival), melanoma with unknown primary&#xD;
             foci;&#xD;
&#xD;
          5. The primary lesion is not completely resected;&#xD;
&#xD;
          6. Staging examination indicated residual or metastatic tumor;&#xD;
&#xD;
          7. Female patients who are pregnant or lactating, or of childbearing potential but not&#xD;
             using appropriate contraceptive measures;&#xD;
&#xD;
          8. Currently having serious and uncontrolled acute infection; or suppurative infection&#xD;
             and chronic infection with prolonged wound healing;&#xD;
&#xD;
          9. Having serious heart disorder, including cardiac failure congestive, uncontrollable&#xD;
             high-risk arrhythmia, unstable angina pectoris, infarct myocardial, severe cardiac&#xD;
             valve disease and refractory hypertension;&#xD;
&#xD;
         10. Having neurological, mental disease or mental disorder that can not be easily&#xD;
             controlled, poor compliance, inability to cooperate and narrate therapeutic response;&#xD;
&#xD;
         11. Patients with other malignant tumors at the same time;&#xD;
&#xD;
         12. Patients paticipated in other clinical trials at the same time;&#xD;
&#xD;
         13. Positive HIV; positive HCV; positive HBsAg or HBcAb whilst positive HBV DNA copies&#xD;
             detected (limit of quantitation 500 IU/mL);&#xD;
&#xD;
         14. Active autoimmune diseases requiring systemic treatment in the past two years (e.g.,&#xD;
             use of disease-regulating drug, corticosteroid or immunosuppressant), relevant&#xD;
             replacement therapy is allowed (e.g., thyroxine, insulin or physiological&#xD;
             corticosteroid replacement therapy for renal or pituitary insufficiency);&#xD;
&#xD;
         15. Having received live vaccine within 4 weeks prior to the start of treatment;&#xD;
&#xD;
         16. Other severe, acute or chronic medical diseases or mental diseases or abnormalities in&#xD;
             laboratory examination possibly increasing the relevant risk in study participation or&#xD;
             possibly interfering the interpretation of study results as judged by the&#xD;
             investigators..&#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>Jun Guo</last_name>
    <phone>86 010 88196951</phone>
    <email>guoj307@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jun Guo</last_name>
      <phone>010-88196951</phone>
      <email>guoj307@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>January 9, 2022</last_update_submitted>
  <last_update_submitted_qc>January 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University Cancer Hospital &amp; Institute</investigator_affiliation>
    <investigator_full_name>Jun Guo</investigator_full_name>
    <investigator_title>Associate Director of Beijing University Cancer Hospital</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04462965
org study id: JS001-ISS-CO148
nct id: NCT04462965
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
A mucosal melanoma postoperative adjuvant treatment of multicenter, randomized, double-blind,
      placebo-controlled phase II study, evaluation of mucosal melanoma patients accept completely
      resected, Toripalima Combined with Temozolomide and Cisplatin postoperative adjuvant therapy
      efficacy and safety
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: RFS assessment per RECIST 1.1.
time frame: 2 years
description: To Compare the recurrence free survival (RFS) per response evaluation crieria in solid tumors(RECIST 1.1) in subjects of the postoperative adjuvant treatment of completely resected mucosal melanoma treated between Toripalima combined with Temozolomide and Cisplatin and placebo combined with Temozolomideand Cisplatin .
measure: RFS assessment per RECIST1.1 in 1 year and 2 year;
time frame: 2 years
description: 1 year and 2 year recurrence free survival rate of completely resected mucosal melanoma with postoperative adjuvant treatment, will be assessed using RECIST1.1 to evaluate tumor recurrence.
measure: DMFS assessed by investigator per RECIT1.1;
time frame: 2 years
description: Distant metastasis free survival (DMFS) of completely resected mucosal melanoma with postoperative adjuvant treatment per RECIST 1.1;
measure: Overall survival (OS) per death time;
time frame: 2 years
description: Overall survival (OS) of completely resected mucosal melanoma with postoperative adjuvant treatment per death time;
measure: .Incidence and grade of AEs and SAEs related to study drugs per NCI-CTCAE version 5.0, AEs ≥ grade 3 related to the study drugs.
time frame: 2 years
description: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 for safty evaluation.
arm group label: Test group
arm group type: Experimental
description: Toripalima Combined with Temozolomide and Cisplatin. Toripalima3 mg/kg intravenous infusion, administered once every 2 weeks (1 treatment cycle every 2 weeks) for a maximum of 1 year. Temozolomide, Oral 200mg/m2 1-5 days and Cisplatin, Iv infusion 25 mg/m2/d for a period of 1 to 3 days, 28 days for 1 cycle, lasting 6 cycles;
arm group label: Placebo group
arm group type: Placebo Comparator
description: Placebo Combined with Temozolomide and Cisplatin. Toripalima3 mg/kg intravenous infusion, administered once every 2 weeks (1 treatment cycle every 2 weeks) for a maximum of 1 year. Temozolomide, Oral 200mg/m2 1-5 days and Cisplatin, Iv infusion 25 mg/m2/d for a period of 1 to 3 days, 28 days for 1 cycle, lasting 6 cycles;
intervention type: Combination Product
intervention name: Toripalimab
description: Injection,Specification 240mg/6ml, 3 mg/kg for the dose, iV, every 2 weeks a dose cycle, up to 1 year; Temozolomide: 100mg or 20mg, Every 4 weeks a dose cycle, up to 6 cycles Cisplatin: Injection, 20mg,Every 4 weeks a dose cycle, up to 6 cycles
arm group label: Test group
intervention type: Combination Product
intervention name: Temozolomide
description: Placebo：Injection,Specification 240mg/6ml, 3 mg/kg for the dose, iV, every 2 weeks a dose cycle, up to 1 year; Temozolomide: 100mg or 20mg, Every 4 weeks a dose cycle, up to 6 cycles Cisplatin: Injection, 20mg,Every 4 weeks a dose cycle, up to 6 cycles
arm group label: Placebo group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jun Guo
phone: 86 010 88196951
email: guoj307@126.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking University Cancer Hospital & Institute
investigator full name: Jun Guo
investigator title: Associate Director of Beijing University Cancer Hospital
mesh term: Melanoma
mesh term: Temozolomide