A Randomized, Open-label, Multi-center Phase III Study Designed to Evaluate the Safety and Efficacy of E10A in Patients With Recurrent/Unresectable Squamous Cell Carcinoma of the Head and Neck Region
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 540
- 试验地点
- 1
- 主要终点
- Time to progression
研究概览
简要总结
Recombinant human endostatin adenovirus injection is a novel anti-tumor gene therapy drug. E10A contains a recombinant human endostatin gene with the second-generation recombinant adenovirus as its vector. After transfection tumor cells. E10A expresses human endostatin, which inhibits vascular endothelial cell proliferation and tumor angiogenesis, and blocks tumor blood supply, thereby specifically inhibiting tumor growth and inducing apoposis of tumor cells. Both pre-clinical and animal models have demonstrated the anti-tumor activities of E10A. The safety and efficacy of E10A in treating head and neck cancer has also been demonstrated in Phase I and Phase II studies.
详细描述
Phase II Clinical Study From March 2008 to December 2010 Safety and efficacy of intratumoral injections of E10A to cisplatin and paclitaxel was evaluated a multicenter, open-label, randomized clinical study in patients with advanced head and neck squamous cell carcinoma.
136 eligible patients were recruited and randomly assigned. Patients with locally advanced or metastatic head and neck squamous cell carcinoma or nasopharyngeal carcinoma not suitable for operation or radiotherapy were randomly assigned to receive E10A plus chemotherapy every 21 for a maximum of six cycles or to receive chemotherapy only.
The primary end point was the objective response rate (RR), defined as the proportion of patients who had a complete response (CR) or partial response (PR) at the target tumor lesion. The secondary end points were the objective disease control rate (DCR, or stable disease (SD) + PR + CR at the target tumor lesion), the overall RR, the overall DCR, OS, and progression-free survival (PFS).
The administration of E10A benefited some subgroups of patients. In the HNSCC patients, the objective RR was 36.5% (15/41) with E10A administration, exhibiting a trend of exceeding the rate of 20.0% (7/35) in the control group (P = 0.090; OR: 0.43), whereas the objective RR was 44.4% (12/27) versus 40.6% (13/32) in the NPC patients (P = 0.487; OR: 0.86). Patients who had previously received chemotherapy in the E10A group had a 44.8% (12/29) objective RR, whereas patients in the control group had only a 22.6% objective RR (7/31; P = 0.06, OR: 0.36). In contrast, patients without previous chemotherapy had a similar RR in both groups (34.3 versus 39.4%; P = 0.426, OR: 1.25).
The difference in the Kaplan-Meier estimates of PFS favored chemotherapy plus E10A, which resulted in a 3.43-month improvement. With a median follow-up of 10.47 months, the median PFS was 3.60 months (interquartile range: 2.60-7.63) in the control group and 7.03 months (interquartile range: 3.27-13.73) in the E10A group. As The median PFS was 3.60 months (interquartile range: 2.60-7.63) in the control group and 7.03months (interquartile range: 3.27-13.73) in the E10A group.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients older than 18 years with histologically or cytologically proven locoregionally advanced or metastatic HNSCC (excluding NPC) not suitable for operation or radiotherapy
- •A life expectancy≧12 weeks.
- •Patients were required to have at least one measurable (by imaging or photograph complied RECIST) lesion with the largest diameter ≧2 cm and suitable for the intratumoral injection of E10A,
- •Not received chemotherapy, radiotherapy, or biotherapy within 4 weeks.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-
- •Adequate bone marrow,renal, and liver functions.
排除标准
- •Known allergies to the study drug.
- •The presence of important blood vessels/nerves or ulceration in the target lesion not suitable for injection.
- •Tumor relapses within 6 months after paclitaxel chemotherapy.
- •Severe coagulation disorders or bleeding tendency.
- •Severe uncontrolled medical conditions.
- •Recent history of myocardial infarction acute infection, pregnancy or lactation, or symptomatic brain metastases
- •A history of corticosteroids or immunosuppressives use within four weeks of study entry
- •Received any chemotherapy or radiotherapy within four weeks of study entry
研究组 & 干预措施
Combination therapy
E10A+chemotherapy group (360 subjects):
- E10A (Endostatins) of 1.0×1012VP on day 1 and 6
- Paclitaxel Injection 160mg/m2 on day 3
- Cisplatin Injection 25mg/m2 on day 3, 4, and 5. Repeat every 21 days.
干预措施: Cisplatin injection (Drug)
Combination therapy
E10A+chemotherapy group (360 subjects):
- E10A (Endostatins) of 1.0×1012VP on day 1 and 6
- Paclitaxel Injection 160mg/m2 on day 3
- Cisplatin Injection 25mg/m2 on day 3, 4, and 5. Repeat every 21 days.
干预措施: Endostatins (Drug)
Combination therapy
E10A+chemotherapy group (360 subjects):
- E10A (Endostatins) of 1.0×1012VP on day 1 and 6
- Paclitaxel Injection 160mg/m2 on day 3
- Cisplatin Injection 25mg/m2 on day 3, 4, and 5. Repeat every 21 days.
干预措施: Paclitaxel injection (Drug)
Chemotherapy
Chemotherapy-alone group (180 subjects):
- Paclitaxel Injection 160mg/m2 on day 1
- Cisplatin Injection 25mg/m2 on day 1, 2, and 3. Repeat every 21 days
干预措施: Paclitaxel injection (Drug)
Chemotherapy
Chemotherapy-alone group (180 subjects):
- Paclitaxel Injection 160mg/m2 on day 1
- Cisplatin Injection 25mg/m2 on day 1, 2, and 3. Repeat every 21 days
干预措施: Cisplatin injection (Drug)
结局指标
主要结局
Time to progression
时间窗: Up to 24 weeks
Time to progression is defined as the time from randomization until objective tumor progression as verified for the first time
次要结局
- Change in Overall response rate (CR+PR)(Up to 24 weeks, from date of randomization until the date of first documented progression)
- Chang in disease control rate (CR+PR+SD)(Up to 24 weeks, From date of randomization until the date of first documented progression)
- Incidence of Treatment-Emergent Adverse Events (Safety and tolerability)(Up to 32 weeks, from date of randomization until the date of first documented progression or date)
- Overall survival(Up to 24 month, through study completion)