A Prospective, Single-arm, Phase II Study of Envafolimab Combined With Chemoradiotherapy and Recombinant Human Endostatin in Locally Advanced Nasopharyngeal Carcinoma.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Complete Response Rate (CRR) after Induction Therapy
研究概览
简要总结
This is a single-center, prospective, single-arm, phase II clinical study, to evaluate the therapeutic efficacy and safety of envafolimab combined with chemoradiotherapy and recombinant human endostatin in patients with locally advanced nasopharyngeal carcinoma.
详细描述
This is a single-center, prospective, single-arm phase II clinical study. Patients with high-risk locally advanced stage III-IVA (8th AJCC/UICC staging) primary nasopharyngeal carcinoma, i.e., T4N+ or N2-3, or pretreatment EBV-DNA ≥4000 copies/ml, or lymph node extra-envelope invasion grade 3 (invasion of muscle skin, etc.) are enrolled. After being screened to meet the enrolment criteria and signing the informed consent form, they will receive 3 cycles of induction therapy with envafolimab combined with recombinant human vascular endothelial inhibitor and gemcitabine and cisplatin, followed by cisplatin-concomitant radiotherapy, and 8 cycles of adjuvant therapy with envafolimab after radiotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ECOG score 0-
- •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.
- •high-risk locally advanced stage III-IVA (8th AJCC/UICC staging), i.e., T4N+ or N2-3, or pretreatment EBV-DNA ≥4000 copies/ml, or lymph node extra-envelope invasion grade 3 (invasion of muscle skin, etc.), 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;
排除标准
- •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.
研究组 & 干预措施
Envafolimab and recombinant human endostatin combined with chemoradiotherapy
Intervention Description: Induction envafolimab combined with recombinant endostatin and gemcitabine and cisplatin therapy for three cycles (every 3 weeks) followed by definitive radiotherapy with concurrent cisplatin chemotherapy. After 4 weeks of the completion of radiotherapy, adjuvant envafolimab therapy will begin every 3 weeks for 8 cycles or continue until progression or unacceptable toxicity.
干预措施: Envafolimab and recombinant human endostatin combined with chemoradiotherapy (Drug)
结局指标
主要结局
Complete Response Rate (CRR) after Induction Therapy
时间窗: From enrollment to the end of induction therapy at 12 weeks
The proportion of patients in whom all target and non-target lesions confirmed at baseline have completely disappeared, as assessed by magnetic resonance imaging (MRI) following the completion of induction therapy.
次要结局
- Objective Response Rate (ORR) after Induction Therapy(From enrollment to the end of induction therapy at 12 weeks)
- Progression Free Survival (PFS)(2 years)
- Overall survival (OS)(2 years)
- Locoregional Relapse-Free Survival (LRRFS)(2 years)
- Distant metastases-Free survival (DMFS)(2 years)
- Incidence rate of adverse events (AEs)(through study completion, an average of 1 year)
研究者
JiangDong Sui
Deputy Director of Chongqing University Cancer Hospital
Chongqing University Cancer Hospital