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Envafolimab Combined With Chemoradiotherapy and Recombinant Human Endostatin for LA-NPC.

Primary Purpose

Nasopharyngeal Carcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Envafolimab and recombinant human endostatin combined with chemoradiotherapy
Sponsored by
Chongqing University Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: ECOG score 0-1. Aged 18-65 years, male or non-pregnant female; Pathologically confirmed diagnosis of nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated, WHO type II or III) without the need to detect MSI and dMMR status. Stage III-IVA (8th AJCC/UICC), including T1-2 N2-3/T3N1-3/T4N0-3, treatment-naive nasopharyngeal carcinoma patients. MRI data of nasopharynx and neck before enrollment, and measurable lesions; Agree to provide a previously stored tumor tissue specimen or biopsy to collect tumor lesion tissue and send it to the central laboratory for PD-L1 IHC testing. Agree to undergo EBV antibody and EBV-DNA quantitative testing before receiving treatment. Hematology: WBC ≥ 4000/μL, neutrophils ≥ 2.000/μL, hemoglobin ≥ 9 g/dL, platelets ≥ 100,000/μL; Liver function: ALT, AST < 1.5 times the upper limit of normal (ULN), total bilirubin < 1.5 × ULN; Renal function: serum creatinine < 1.5 × ULN. Patients have signed the informed consent form and are willing and able to comply with the study plan visits, treatment plan, laboratory tests and other study procedures; Exclusion Criteria: Patients with recurrent nasopharyngeal carcinoma and distant metastasis. Pathology was keratinizing squamous cell carcinoma (WHO classification type I). Patients who have undergone radiotherapy or systemic chemotherapy; Pregnant or lactating women, in the reproductive period without effective contraceptive measures; HIV positive. Having had other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ); Patients who have been treated with inhibitors of immune regulatory points (CTLA-4, PD-1, PD-L1, etc.); Patients need long-term use of immunosuppressive drug therapy, or systemic or local use of immunosuppressive doses of corticosteroids complications; Patients with immunodeficiency disease, history of organ transplantation (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo or complete remission of asthma in childhood, without any intervention after adulthood can be included; patients with asthma requiring bronchodilators for medical intervention can not be included; Use of excessive doses of glucocorticoids within 4 weeks. Laboratory test values within 7 days before enrollment do not meet the relevant criteria; Patients with significantly low heart, liver, lung, kidney and bone marrow function. Any other diseases or conditions are contraindications to recombinant human vascular endothelial inhibitors, chemoradiotherapy, immunotherapy (such as active phase of infection, within 6 months after myocardial infarction, symptomatic heart disease including unstable angina pectoris, congestive heart failure or uncontrolled arrhythmia, immunosuppressive therapy); Any arterial thrombosis, embolism or ischemia within 6 months before inclusion for treatment, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack; Severe, uncontrolled medical illness and infection. Concurrent use of other investigational drugs or ongoing other clinical trials; Refusing or unable to sign the informed consent form to participate in the trial. Personality or mental disorders, no civil capacity or limited civil capacity; Hepatitis B surface antigen (HBsAg) positive and peripheral blood hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 1000cps/ml. Patients who tested positive for HCV antibody were included in the study only if they tested negative for HCV RNA by polymerase chain reaction.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Envafolimab and recombinant human endostatin combined with chemoradiotherapy

    Arm Description

    Intervention Description: Induction envafolimab combined with recombinant endostatin and gemcitabine and cisplatin therapy for three cycle (every 3 weeks) followed by definitive radiotherapy with or without concurrent cisplatin chemotherapy. After 4weeks of the completion of radiotherapy, adjuvant envafolimab therapy will begin every 3 weeks for 5 cycles or continue until progression or unacceptable toxicity.

    Outcomes

    Primary Outcome Measures

    Progress-free survival (PFS)
    Defined as the time interval from randomization to tumor progression or death due to any cause. The appearance of new lesions was used as a criterion for progression, and the landmark time point of progression was the date when measurable new lesions were first observed.

    Secondary Outcome Measures

    Overall survival (OS)
    Overall survival is measured from randomization until death due to any cause or the latest known date alive.
    Recurrence-free survival(RFS)
    Defined as the time from randomization to documented disease recurrence (distant metastasis or local disease recurrence) or death from any cause, whichever occurs first.
    Locoregional Relapse-Free Survival (LRFS)
    Defined as the time interval from randomization to the first occurrence of recurrence, or to the last follow-up time if there was no recurrence.
    Distant metastases-Free survival (DMFS)
    Defined as the time interval from randomization to the occurrence of distant metastasis after treatment, or the time to the last follow-up or death due to other causes if there was no distant metastasis.
    Incidence rate of adverse events (AEs)
    Analysis of adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs, according to the Common Terminology Criteria for Adverse Events, version 5.0.
    Compliance
    Refers to patients taking the drug according to the prescribed dose and course of treatment, as well as the degree of compliance with the study protocol during the implementation by the investigator.

    Full Information

    First Posted
    September 23, 2023
    Last Updated
    September 23, 2023
    Sponsor
    Chongqing University Cancer Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06059261
    Brief Title
    Envafolimab Combined With Chemoradiotherapy and Recombinant Human Endostatin for LA-NPC.
    Official Title
    A Prospective, Single-arm, Phase II Study of Envafolimab Combined With Chemoradiotherapy and Recombinant Human Endostatin in Locally Advanced Nasopharyngeal Carcinoma.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 1, 2023 (Anticipated)
    Primary Completion Date
    October 1, 2027 (Anticipated)
    Study Completion Date
    October 1, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Chongqing University Cancer Hospital

    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 single-center, prospective, single-arm, phase II clinical study, with the purpose to evaluate the therapeutic efficacy and safety of envafolimab combined with chemoradiotherapy and recombinant human endostatin in patients with locally advanced nasopharyngeal carcinoma.
    Detailed Description
    Patients with locally advanced nasopharyngeal carcinoma will receive 3 cycles of induction therapy with envafolimab combined with recombinant endostatin and gemcitabine and cisplatin, followed by 2 cycles of sequential envafolimab and recombinant human endostatin combined with radiotherapy alone in the low-risk group (with undetectable EBV DNA and CR/PR after induction therapy), or 2 cycles of sequential envafolimab and recombinant human endostatin combined with concurrent chemoradiotherapy in the high-risk group (with detectable EBV DNA or SD/PD after induction therapy), and finally 5 cycles of adjuvant therapy with envafolimab.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Nasopharyngeal Carcinoma

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Envafolimab and recombinant human endostatin combined with chemoradiotherapy
    Arm Type
    Experimental
    Arm Description
    Intervention Description: Induction envafolimab combined with recombinant endostatin and gemcitabine and cisplatin therapy for three cycle (every 3 weeks) followed by definitive radiotherapy with or without concurrent cisplatin chemotherapy. After 4weeks of the completion of radiotherapy, adjuvant envafolimab therapy will begin every 3 weeks for 5 cycles or continue until progression or unacceptable toxicity.
    Intervention Type
    Drug
    Intervention Name(s)
    Envafolimab and recombinant human endostatin combined with chemoradiotherapy
    Intervention Description
    Induction treatment phase:Envafolimab administered by subcutaneous injection on day 1 every 3 weeks at 300 mg for 3 cycles, cisplatin administered by intravenous infusion on day 1 of each cycle at 80 mg/m2 every 3 weeks for 3 cycles, gemcitabine was administered by intravenous infusion on days 1 and 8 of each cycle at 1 g/m2 every 3 weeks for 3 cycles, recombinant human endostatin was administered on day 1 every 3 weeks at 210 mg for 3 cycles. Concurrent treatment phase: Envafolimab was administered by subcutaneous injection on day 1 every 3 weeks at 300 mg for 2 cycles. For high risk group, cisplatin was administered by intravenous infusion on day 1 of each cycle at 100mg/m2 every 3 weeks for 2 cycles, for low risk group, there is no need for chemotherapy. Adjuvant treatment Phase: Envafolimab was administered on day 1 every 3 weeks at 300 mg for 5 cycles as a subcutaneous injection. Intensity-modulated radiotherapy: 69.96Gy/33fractions/7weeks,5 fractions/week, 1 fraction/day.
    Primary Outcome Measure Information:
    Title
    Progress-free survival (PFS)
    Description
    Defined as the time interval from randomization to tumor progression or death due to any cause. The appearance of new lesions was used as a criterion for progression, and the landmark time point of progression was the date when measurable new lesions were first observed.
    Time Frame
    3 years
    Secondary Outcome Measure Information:
    Title
    Overall survival (OS)
    Description
    Overall survival is measured from randomization until death due to any cause or the latest known date alive.
    Time Frame
    3 years
    Title
    Recurrence-free survival(RFS)
    Description
    Defined as the time from randomization to documented disease recurrence (distant metastasis or local disease recurrence) or death from any cause, whichever occurs first.
    Time Frame
    3 years
    Title
    Locoregional Relapse-Free Survival (LRFS)
    Description
    Defined as the time interval from randomization to the first occurrence of recurrence, or to the last follow-up time if there was no recurrence.
    Time Frame
    3 years
    Title
    Distant metastases-Free survival (DMFS)
    Description
    Defined as the time interval from randomization to the occurrence of distant metastasis after treatment, or the time to the last follow-up or death due to other causes if there was no distant metastasis.
    Time Frame
    3 years
    Title
    Incidence rate of adverse events (AEs)
    Description
    Analysis of adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs, according to the Common Terminology Criteria for Adverse Events, version 5.0.
    Time Frame
    3 years
    Title
    Compliance
    Description
    Refers to patients taking the drug according to the prescribed dose and course of treatment, as well as the degree of compliance with the study protocol during the implementation by the investigator.
    Time Frame
    3 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: ECOG score 0-1. Aged 18-65 years, male or non-pregnant female; Pathologically confirmed diagnosis of nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated, WHO type II or III) without the need to detect MSI and dMMR status. Stage III-IVA (8th AJCC/UICC), including T1-2 N2-3/T3N1-3/T4N0-3, treatment-naive nasopharyngeal carcinoma patients. MRI data of nasopharynx and neck before enrollment, and measurable lesions; Agree to provide a previously stored tumor tissue specimen or biopsy to collect tumor lesion tissue and send it to the central laboratory for PD-L1 IHC testing. Agree to undergo EBV antibody and EBV-DNA quantitative testing before receiving treatment. Hematology: WBC ≥ 4000/μL, neutrophils ≥ 2.000/μL, hemoglobin ≥ 9 g/dL, platelets ≥ 100,000/μL; Liver function: ALT, AST < 1.5 times the upper limit of normal (ULN), total bilirubin < 1.5 × ULN; Renal function: serum creatinine < 1.5 × ULN. Patients have signed the informed consent form and are willing and able to comply with the study plan visits, treatment plan, laboratory tests and other study procedures; Exclusion Criteria: Patients with recurrent nasopharyngeal carcinoma and distant metastasis. Pathology was keratinizing squamous cell carcinoma (WHO classification type I). Patients who have undergone radiotherapy or systemic chemotherapy; Pregnant or lactating women, in the reproductive period without effective contraceptive measures; HIV positive. Having had other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ); Patients who have been treated with inhibitors of immune regulatory points (CTLA-4, PD-1, PD-L1, etc.); Patients need long-term use of immunosuppressive drug therapy, or systemic or local use of immunosuppressive doses of corticosteroids complications; Patients with immunodeficiency disease, history of organ transplantation (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo or complete remission of asthma in childhood, without any intervention after adulthood can be included; patients with asthma requiring bronchodilators for medical intervention can not be included; Use of excessive doses of glucocorticoids within 4 weeks. Laboratory test values within 7 days before enrollment do not meet the relevant criteria; Patients with significantly low heart, liver, lung, kidney and bone marrow function. Any other diseases or conditions are contraindications to recombinant human vascular endothelial inhibitors, chemoradiotherapy, immunotherapy (such as active phase of infection, within 6 months after myocardial infarction, symptomatic heart disease including unstable angina pectoris, congestive heart failure or uncontrolled arrhythmia, immunosuppressive therapy); Any arterial thrombosis, embolism or ischemia within 6 months before inclusion for treatment, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack; Severe, uncontrolled medical illness and infection. Concurrent use of other investigational drugs or ongoing other clinical trials; Refusing or unable to sign the informed consent form to participate in the trial. Personality or mental disorders, no civil capacity or limited civil capacity; Hepatitis B surface antigen (HBsAg) positive and peripheral blood hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 1000cps/ml. Patients who tested positive for HCV antibody were included in the study only if they tested negative for HCV RNA by polymerase chain reaction.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xin Zhang, Ph.D, M.D.
    Phone
    18323063006
    Email
    zhangxin9964@126.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jiang D Sui, Ph.D, M.D.
    Phone
    13594190011
    Email
    jiangdong.sui@cqu.edu.cn
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jiang D Sui, Ph.D, M.D.
    Organizational Affiliation
    Chongqing University Cancer Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
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    Envafolimab Combined With Chemoradiotherapy and Recombinant Human Endostatin for LA-NPC.

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