A Phase II/III Randomized Trial of Comparison of Survival Benefit of Administration of PD1/PDL1/CTLA4 Inhibitors or Their Combinations Via Neck Artery or Intratumor Versus Vein Infusion for Immunotherapy of HNC
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
This trial was designed to investigate the survival outcomes, response rates, and safety of patients with advanced Head/Neck Squamous cancer via intra-tumor or intra-artery versus vein infusion of PD1/PDL1/CTLA4 inhibitor or their combinations.
详细描述
Head/Neck cancer is a kind of hard-to-treat malignancy worldwide and its overall survival rate is still low. PD1/PDL1/CTLA4 inhibitors are widely used to treat various of cancers now. Delivery of antibody drugs through interventional approaches including intra-tumor or intra-artery, based on the theory of "first pass effect" of drug, can significantly increase the local drug concentration of the tumor, improve the efficacy, and reduce systemic adverse reactions.
To the investigator's knowledge, no studies have been developed on the survival benefit of neck artery infusion or intra-tumor injection of immunotherapeutic agents in patients with advanced HNC. This phase II-III clinical trial was designed to compare the effects of PD1/PDL1/CTLA4 inhibitor or their combinations via IA/IT and IV on the survival benefit of patients with advanced HNC, including ORR, DCR, median survival time, and safety.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cytohistological confirmation is required for diagnosis of HNC.
- •Signed informed consent before recruiting.
- •Age between 18 to 80 years with estimated survival over 3 months.
- •ECOG score < 2
- •Tolerable coagulation function or reversible coagulation disorders
- •Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR < 2.3 or PT < 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin > 28 g/L；Total bilirubin < 51 μmol/L
- •At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.
- •Patients with advanced HNC which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection and other treatment.
- •Birth control.
- •Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
排除标准
- •Patients participated in other clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
- •Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
- •Patients accompanied with other tumors or past medical history of malignancy;
- •Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;
- •Patients have poor compliance.
- •Any contraindications for neck artery infusion procedure:
- •A. Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 50%).
- •B. Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C. Known severe atheromatosis. D. Known uncontrolled blood hypertension (> 160/100 mm/Hg).
- •Allergic to adriamycin chemotherapy drugs，contrast agent or lipiodol;
- •Any agents which could affect the absorption or pharmacokinetics of the study drugs
- •Subjects unable to suffer the discomfort of the artery infusion procedure
研究组 & 干预措施
PD1/PDL1/CTLA4 inhibitor or their combinations infusion via neck artery
Interventional technique is used to localize neck artery to infuse the inhibitor or their combinations directly into tumor.
干预措施: PD1/PDL1/CTLA4 inhibitors (Drug)
PD1/PDL1/CTLA4 inhibitor or their combinations infusion via peripheral vein
Routine peripheral vein infusion of PD1/PDL1/CTLA4 inhibitor or their combinations is performed.
干预措施: PD1/PDL1/CTLA4 inhibitors (Drug)
PD1/PDL1/CTLA4 inhibitor or their combinations infusion via intra-tumor penetration
Interventional technique is used to intra-tumor injection of the inhibitor or their combinations directly into tumor.
干预措施: PD1/PDL1/CTLA4 inhibitors (Drug)
结局指标
主要结局
Overall survival
时间窗: 2 years
Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.
次要结局
- Progression-free survival(2 years)
- Adverse event rate(2 years)