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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Prospective, Single-arm, Phase II Study of Envafolimab Combined With Chemoradiotherapy and Recombinant Human Endostatin in Locally Advanced Nasopharyngeal Carcinoma.

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Envafolimab and recombinant human endostatin combined with chemoradiotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Envafolimab and recombinant human endostatin combined with chemoradiotherapy<br>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. | Drug: Envafolimab and recombinant human endostatin combined with chemoradiotherapy<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Overall survival is measured from randomization until death due to any cause or the latest known date alive. | 3 years | 
| 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. | 3 years | 
| 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. | 3 years | 
| 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. | 3 years | 
| 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. | 3 years | 
| 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. | 3 years |