PD-1 Inhibitor and Bevacizumab Replace Cisplatin in Induction, Concurrent, and/or Adjuvant Therapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- grade ≥3 nasopharyngeal necrosis or hemorrhage
研究概览
简要总结
At present, the treatment regimen of locally advanced nasopharyngeal carcinoma still needs to be further improved, and the focus of improvement lies in "replacing cisplatin with high-efficiency and low-toxicity treatment regimen". Considering the synergistic effect among radiotherapy, immunotherapy and anti-angiogenesis therapy, we chose PD-1 inhibitor combined with bevacizumab to replace cisplatin chemotherapy.
详细描述
We plan to use PD-1 inhibitor combined with bevacizumab to replace cisplatin (induction + concurrent ± adjuvant) in patients with locally advanced nasopharyngeal carcinoma. Considering the safety of the original study, we will set up two groups for the adjuvant treatment stage: one group will only use PD-1 inhibitor at the adjuvant treatment stage (low risk group), and the other group will use bevacizumab +PD-1 inhibitor combined treatment (high risk group). Once the efficacy and safety of this protocol are confirmed, it may provide a new treatment option for locally advanced nasopharyngeal carcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Voluntary participation with Written informed consent.
- •Age ≥ 18 years and ≤ 65 years.
- •Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type).
- •Original clinical staged as III-IVa (according to the 8th AJCC edition).
- •Stage III patients should meet the criteria of EBV DNA≥4000 cps/ml.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or
- •Patients must have adequate organ function:
- •White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN),serum total bilirubin (TBIL) ≤2.0 times the upper limit of normal (ULN) .
- •Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5× upper limit of normal value.
- •INR, APTT≤1.5 x ULN.
排除标准
- •Subjects with recurrent or metastatic nasopharyngeal carcinoma.
- •Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
- •Prior therapy with systemic therapy for nasopharyngeal carcinoma.
- •Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.
- •Prior exposure to antiangiogenic agents.
- •Tumor invasion to the intracranial with clinical symptoms accompanied by cerebral edema, requiring hormone therapy.
- •Any grade ≥2 bleeding event (according to CTCAE 5.0) occurred within 4 weeks prior to enrollment.
- •Subjects with an active, known or suspected autoimmune disease.
- •Subjects with clinically significant cardiovascular and cerebrovascular diseases.
- •Subjects with high blood pressure who cannot be controlled well with antihypertensive drugs.
- •Subjects with previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency.
- •Subjects with arterial / venous thrombosis events occurred within 6 months of the first dose.
- •Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.
- •Seropositivity for human immunodeficiency virus (HIV).
- •Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).
研究组 & 干预措施
low risk
Patients will receive induction therapy with toripalimab plus bevacizumab and gemcitabine every 3 weeks for 3 cycles before radiotherapy, then followed by IMRT and concurrent therapy with toripalimab plus bevacizumab for 2 cycles, then followed by adjuvant therapy with toripalimab every 3 weeks for a maximum of 1 year after radiotherapy.
干预措施: Bevacizumab+Toripalimab+gemcitabine, adjuvant with Toripalimab (Drug)
high risk
Patients will receive induction therapy with toripalimab plus bevacizumab and gemcitabine every 3 weeks for 3 cycles before radiotherapy, then followed by IMRT and concurrent therapy with toripalimab plus bevacizumab for 2 cycles, then followed by adjuvant therapy with toripalimab and bevacizumab every 3 weeks for a maximum of 1 year after radiotherapy.
干预措施: Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and Toripalimab (Drug)
结局指标
主要结局
grade ≥3 nasopharyngeal necrosis or hemorrhage
时间窗: At the end of each cycle (each cycle is 21 days)
Incidence of nasopharyngeal necrosis or massive hemorrhage (grade ≥3). Grade ≥3 hemorrhage: Grade 3, Transfusion indicated; invasive intervention indicated; hospitalization. Grade 4, Life-threatening consequences; urgent intervention indicated (e.g., tracheotomy or intubation). Grade 5, death. Grade ≥3 nasopharyngeal necrosis: Grade 3, Severe pain; unable to adequately aliment or hydrate orally; limiting self care ADL. Grade 4, Life-threatening consequences; urgent intervention indicated. Grade 5, death.
次要结局
- Objective response rate(3 weeks after indution therapy; 3 months after concurrent therapy)
- Progression-free survival(3 year)
- Overall survival(3 year)
- Locoregional failure-free survival (LRRFS)(3 year)
- Distant metastasis-free survival (DMFS)(3 year)
- Incidence rate of adverse events (AEs)(3 year)
研究者
Ming-Yuan Chen
Chief physician, Proffessor
Sun Yat-sen University