Neoadjuvant Personalized Anti-PD-1 Therapy With Combination of Anti-VEGFR Therapy in Locally Advanced and Resectable Oral Squamous Cell Carcinoma: A Randomized Controlled Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- 2-year disease-free survival rate
研究概览
简要总结
To evaluate the efficacy of neoadjuvant anti-PD-1 plus anti-VEGFR therapy for patients with locally advanced and resectable oral squamous cell carcinoma, and the CPS>10 in the biopsy samples.
详细描述
In the previous "Icemelting" trial, neoadjuvant anti-PD-1 plus anti-VEGFR therapy was used in 20 patients with locally advanced and resectable oral squamous cell carcinoma (OSCC), and the neoadjuvant therapy was well-tolerated, with no grade 3-4 toxicity. The MPR rate was 40% (8/20), including 5% (1/20) pathological complete response; furthermore, in the patients with CPS>10, the MPR rate was 100%. As we know, the MPR might transfer to survival benefit in the patients received neoadjuvant therapy. Therefore, in this randomized phase II trial, we aimed to evaluate the survival benefit of neoadjuvant anti-PD-1 plus anti-VEGFR therapy in the patients with locally advanced OSCC and CPS>10 (Icemelting-2 trial). A total of 46 patients will be enrolled in this trial, and the primary endpoint is 2-year disease-free survival rate. The neoadjuvant therapy arm will receive three cycles of Carrelizumab plus Apatinib with 14 days each, followed by the standard treatment of surgery and postoperative adjuvant therapy. The control arm will received the standard treatment of surgery and postoperative adjuvant therapy.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18 to 75
- •Gender: Male and female
- •ECOG Score: 0-2
- •Histologically confirmed primary oral squamous cell carcinoma (including tongue, gingival, buccal, oral base, hard palate, posterior molar area)
- •Clinical stage III/IVA (cT1-2/N1-2/M0 or cT3-4a/N0-2 /M0, AJCC 8th)
- •The combined positive score (CPS score) of PD-L1 expression > 10
- •Has signed informed consent
排除标准
- •Toxicity of ≥ grade 2 (CTCAE 5.0) that has not subsided due to previous anticancer therapy
- •Obvious cardiovascular abnormalities (such as myocardial infarction, superior vena cava syndrome, ≥ grade 2 heart disease diagnosed according to the NYHA classification criteria within 3 months prior to enrollment)
- •Active severe clinical infection (> NCI-CTCAE Version 5.0 level 2 infection)
- •Uncontrollable hypertension (systolic blood pressure > after antihypertensive medication; 150mmHg and/or diastolic blood pressure > 90mmHg) or clinically significant (such as activity) cardiovascular disease, such as cerebrovascular accident (≤ 6 months before screening), myocardial infarction (≤ 6 months before screening), unstable angina, congestive heart failure rated class II or above by NYHA, or severe arrhythmias that cannot be controlled or have a potential impact on trial treatment
- •Blood routine examination: WBC < 3,000/mm3, hemoglobin < 8g/L, platelet < 80,000/mm3
- •Liver function: ALAT/ASAT > 2.5 times the normal upper limit, bilirubin > 1.5 times the normal upper limit
- •Renal function: serum creatinine > 1.5 times the normal upper limit
- •Has a history of maxillofacial and neck radiotherapy
- •Pregnant or lactating women
- •Participation in other clinical studies within 30 days prior to enrollment
- •Other conditions that the investigator considers inappropriate for participation
研究组 & 干预措施
Neoadjuvant arm
The patients received three cycles of neoadjuvant therapy, with 14 days each. Dosage and administration: 200mg Carrelizumab intravenously on the first day of each cycle; Apatinib orally 250mg once a day from the first day of each cycle until the 9th day of the third cycle. Then the patients received the standard treatment of surgery and postoperative adjuvant therapy of radiotherapy or chemoradiotherapy.
干预措施: Camrelizumab (anti-PD-1 inhibitor) (Drug)
Neoadjuvant arm
The patients received three cycles of neoadjuvant therapy, with 14 days each. Dosage and administration: 200mg Carrelizumab intravenously on the first day of each cycle; Apatinib orally 250mg once a day from the first day of each cycle until the 9th day of the third cycle. Then the patients received the standard treatment of surgery and postoperative adjuvant therapy of radiotherapy or chemoradiotherapy.
干预措施: Apatinib (anti-VEGFR inhibitor) (Drug)
结局指标
主要结局
2-year disease-free survival rate
时间窗: 24 months
Disease-free survival was calculated from the date of randomization to tumor recurrence or death from any cause.
次要结局
- 2-year overall survival rate(24 months)
- Major pathological response(3 months)
研究者
Lai-ping Zhong
Professor
Shanghai Jiao Tong University School of Medicine