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Envafolimab Combined With Recombinant Human Endostatin and First-line Chemotherapy Treat of Advanced Mucosal Melanoma

Primary Purpose

Advanced Mucosal Melanoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Envafolimab combined with recombinant human endostatin and first-line chemotherapy
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Mucosal Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥ 18 years old, regardless of gender. Histology and pathology confirmed advanced mucosal melanoma. Gene mutation state is not limited, except BRAFV600 mutation. Has not received first-line treatment for advanced melanoma, and temozolomide and cisplatin have been used in the adjuvant therapy phase, except that the adjuvant therapy phase has been over 6 months or more. Eastern Cancer Cooperation Group (ECOG) physical condition score (PS) 0-1. The estimated survival time is more than 3 months. Within 7 days before screening (including 7 days), the laboratory data were required as follows: neutrophil count ≥ 1.5 × 109 shock L, platelet count ≥ 90 × 109 shock L, hemoglobin ≥ 90g/L (no blood transfusion within 14 days), serum total bilirubin ≤ 1.25x normal upper limit (ULN), ALT and AST ≤ 2.5xULN (patients with liver metastasis ≤ 5xULN); serum creatinine ≤ 1.25xULN. Have at least one measurable focus (RECIST1.1 standard). Subjects (or their legal representatives / guardians) must sign an informed consent form indicating that they understand the purpose of the study, understand the necessary procedures for the study, and are willing to participate in the study. Exclusion Criteria: Patients who have previously used PD-L1 inhibitors, except those who progressed 1 year after the end of adjuvant therapy of PD-L1 monoclonal antibody; Allergic to Envafolimab or recombinant human endostatin and experimental chemotherapeutic drugs; Received any experimental drugs or antineoplastic drugs within 4 weeks before entering the group; There is a risk of bleeding, bleeding events of clinical significance or other taboos in the use of antivascular drugs; There is a history of other tumors in the past five years, except for cured cervical cancer or skin basal cell carcinoma; There are tumor emergencies that require immediate radiotherapy, such as symptomatic brain or meningeal metastasis, bone-related events, etc; Pregnant or lactating women; Fertile women who do not use adequate contraception; Alcohol or drug addiction; Patients with active, or history of autoimmune diseases that may recur (e.g. systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or patients at high risk (such as immunosuppressive therapy required for organ transplants). Except for autoimmune hypothyroidism that requires only hormone replacement therapy or skin diseases that do not require systemic treatment; Patients who need to receive systemic corticosteroids (dose equivalent to > 10mg prednisone / day) or other immunosuppressive drugs within 14 days before enrollment or during the study. The use of topical or inhaled corticosteroids, or short-term (≤ 7 days) use of glucocorticoids for the prevention or treatment of non-autoimmune and infrequent allergic diseases; Important organ failure or other serious diseases, including interstitial pneumonia, clinically related coronary artery disease, cardiovascular disease or myocardial infarction, congestive heart failure, unstable angina pectoris, symptomatic pericardial effusion or unstable arrhythmia within 6 months before admission; A history of human immunodeficiency virus infection, or other acquired, congenital immunodeficiency diseases, or a history of organ transplant or stem cell transplantation; Patients with active chronic hepatitis B or active hepatitis C. HBV carriers, stable hepatitis B (DNA titer ≤ 103copies / ml) and cured hepatitis C patients (HCVRNA negative) can be enrolled in the group; A history of severe neurological or psychiatric illness; severe infection; active disseminated intravascular coagulation or other concomitant diseases that, in the opinion of the researchers, seriously endanger the safety of patients or affect the completion of the study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Envafolimab combined with recombinant human endostatin and first-line chemotherapy

    Arm Description

    Outcomes

    Primary Outcome Measures

    Progression-free Survival (PFS)
    Time from the date of randomization to the date of progressive disease (PD) or death, whichever occurs first.

    Secondary Outcome Measures

    Objective Response Rate (ORR)
    ORR was defined as the percentage of participants with measurable lesions achieving a Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) criteria.
    Disease Control Rate (DCR)
    The proportion of participants who achieves a best overall response of CR, PR or stable disease(SD).
    Duration of Response (DoR)
    The time from the date that response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first.
    Overall Survival (OS)
    OS is defined as the time from enrollment to death from any cause.
    PD-L1 expression from the tissue and peripheral blood samples of the patients
    The tissue and peripheral blood samples of the patients were taken for the determination of PD-L1 expression, and the results were analyzed to find the predictive factors of prognosis or curative effect.
    ctDNA expression from the tissue and peripheral blood samples of the patients
    The tissue and peripheral blood samples of the patients were taken for the determination of ctDNA expression, and the results were analyzed to find the predictive factors of prognosis or curative effect.
    Adverse Events (AEs) according to CTCAE v5.0.
    Adverse Events (AEs) according to CTCAE v5.0.

    Full Information

    First Posted
    September 12, 2023
    Last Updated
    September 15, 2023
    Sponsor
    Fudan University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06041724
    Brief Title
    Envafolimab Combined With Recombinant Human Endostatin and First-line Chemotherapy Treat of Advanced Mucosal Melanoma
    Official Title
    Single-arm II Phase Study of Envafolimab Combined With Recombinant Human Endostatin and First-line Chemotherapy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 18, 2023 (Anticipated)
    Primary Completion Date
    September 18, 2025 (Anticipated)
    Study Completion Date
    March 18, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Fudan University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a phase II, open, single-center study to explore the efficacy and safety of Envafolimab combined with recombinant human endostatin, temozolomide and cisplatin in the treatment of mucosal melanin. At the same time, the tissue and peripheral blood samples of the patients were taken for the determination of PD-L1 expression, ctDNA and other biomarkers and the results were analyzed to find the predictive factors of prognosis or curative effect. Patients with advanced mucosal melanoma who met the inclusion criteria but did not meet the exclusion criteria were enrolled in this study and received 6 cycles of Envafolimab combined with recombinant human endostatin, temozolomide and cisplatin. Patients without progression were then maintained with Envafolimab combined with recombinant human endostatin until disease progression, intolerable adverse reactions, patient death or withdrawal of informed consent. The longest administration time of recombinant human endostatin was no more than 1 year, and that of Envafolimab was not more than 2 years. The efficacy was evaluated for the first time at 6 weeks, every 6 weeks for the following year, and then every 12 weeks until the end of progress or treatment. The examination method was consistent with the baseline; it was expected to be included in the group for 18 months, and clinical observation until disease progression and patient death.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Advanced Mucosal Melanoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    46 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Envafolimab combined with recombinant human endostatin and first-line chemotherapy
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Envafolimab combined with recombinant human endostatin and first-line chemotherapy
    Intervention Description
    Envafolimab: 300mg day1, s.c. Q3W; Recombinant human endostatin: 210mg day1, Intravenous pump for 72 hours, Q3W; Temozolomide: 150 mg/m2 d1-5, i.v. Q3W; Cisplatin: 25 mg/m2 d1-3, i.v. Q3W. All of the above drugs were used for 6 cycles, and then Envafolimab and recombinant human endostatin continued only in patients with no progression in the first stage until disease progression as defined by RECIST1.1, unacceptable toxicity, withdrawal from the study or death, or no more than 2 years.
    Primary Outcome Measure Information:
    Title
    Progression-free Survival (PFS)
    Description
    Time from the date of randomization to the date of progressive disease (PD) or death, whichever occurs first.
    Time Frame
    12 months
    Secondary Outcome Measure Information:
    Title
    Objective Response Rate (ORR)
    Description
    ORR was defined as the percentage of participants with measurable lesions achieving a Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) criteria.
    Time Frame
    12 months
    Title
    Disease Control Rate (DCR)
    Description
    The proportion of participants who achieves a best overall response of CR, PR or stable disease(SD).
    Time Frame
    12 months
    Title
    Duration of Response (DoR)
    Description
    The time from the date that response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first.
    Time Frame
    12 months
    Title
    Overall Survival (OS)
    Description
    OS is defined as the time from enrollment to death from any cause.
    Time Frame
    12 months
    Title
    PD-L1 expression from the tissue and peripheral blood samples of the patients
    Description
    The tissue and peripheral blood samples of the patients were taken for the determination of PD-L1 expression, and the results were analyzed to find the predictive factors of prognosis or curative effect.
    Time Frame
    baseline (When entering the group)
    Title
    ctDNA expression from the tissue and peripheral blood samples of the patients
    Description
    The tissue and peripheral blood samples of the patients were taken for the determination of ctDNA expression, and the results were analyzed to find the predictive factors of prognosis or curative effect.
    Time Frame
    baseline (When entering the group)
    Title
    Adverse Events (AEs) according to CTCAE v5.0.
    Description
    Adverse Events (AEs) according to CTCAE v5.0.
    Time Frame
    12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥ 18 years old, regardless of gender. Histology and pathology confirmed advanced mucosal melanoma. Gene mutation state is not limited, except BRAFV600 mutation. Has not received first-line treatment for advanced melanoma, and temozolomide and cisplatin have been used in the adjuvant therapy phase, except that the adjuvant therapy phase has been over 6 months or more. Eastern Cancer Cooperation Group (ECOG) physical condition score (PS) 0-1. The estimated survival time is more than 3 months. Within 7 days before screening (including 7 days), the laboratory data were required as follows: neutrophil count ≥ 1.5 × 109 shock L, platelet count ≥ 90 × 109 shock L, hemoglobin ≥ 90g/L (no blood transfusion within 14 days), serum total bilirubin ≤ 1.25x normal upper limit (ULN), ALT and AST ≤ 2.5xULN (patients with liver metastasis ≤ 5xULN); serum creatinine ≤ 1.25xULN. Have at least one measurable focus (RECIST1.1 standard). Subjects (or their legal representatives / guardians) must sign an informed consent form indicating that they understand the purpose of the study, understand the necessary procedures for the study, and are willing to participate in the study. Exclusion Criteria: Patients who have previously used PD-L1 inhibitors, except those who progressed 1 year after the end of adjuvant therapy of PD-L1 monoclonal antibody; Allergic to Envafolimab or recombinant human endostatin and experimental chemotherapeutic drugs; Received any experimental drugs or antineoplastic drugs within 4 weeks before entering the group; There is a risk of bleeding, bleeding events of clinical significance or other taboos in the use of antivascular drugs; There is a history of other tumors in the past five years, except for cured cervical cancer or skin basal cell carcinoma; There are tumor emergencies that require immediate radiotherapy, such as symptomatic brain or meningeal metastasis, bone-related events, etc; Pregnant or lactating women; Fertile women who do not use adequate contraception; Alcohol or drug addiction; Patients with active, or history of autoimmune diseases that may recur (e.g. systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or patients at high risk (such as immunosuppressive therapy required for organ transplants). Except for autoimmune hypothyroidism that requires only hormone replacement therapy or skin diseases that do not require systemic treatment; Patients who need to receive systemic corticosteroids (dose equivalent to > 10mg prednisone / day) or other immunosuppressive drugs within 14 days before enrollment or during the study. The use of topical or inhaled corticosteroids, or short-term (≤ 7 days) use of glucocorticoids for the prevention or treatment of non-autoimmune and infrequent allergic diseases; Important organ failure or other serious diseases, including interstitial pneumonia, clinically related coronary artery disease, cardiovascular disease or myocardial infarction, congestive heart failure, unstable angina pectoris, symptomatic pericardial effusion or unstable arrhythmia within 6 months before admission; A history of human immunodeficiency virus infection, or other acquired, congenital immunodeficiency diseases, or a history of organ transplant or stem cell transplantation; Patients with active chronic hepatitis B or active hepatitis C. HBV carriers, stable hepatitis B (DNA titer ≤ 103copies / ml) and cured hepatitis C patients (HCVRNA negative) can be enrolled in the group; A history of severe neurological or psychiatric illness; severe infection; active disseminated intravascular coagulation or other concomitant diseases that, in the opinion of the researchers, seriously endanger the safety of patients or affect the completion of the study.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Zhiguo Luo, M.D
    Phone
    +8621-64175590
    Ext
    8908
    Email
    luozhiguo88@163.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Zhiguo Luo, M.D
    Organizational Affiliation
    Fudan University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Envafolimab Combined With Recombinant Human Endostatin and First-line Chemotherapy Treat of Advanced Mucosal Melanoma

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