E10A for the Treatment of Squamous Cell Carcinoma of the Head and Neck

Phase 3

• Conditions: Head and Neck Neoplasms
• Interventions: Drug: Paclitaxel injection; Drug: Endostatins; Drug: Cisplatin injection

• Registration Number: NCT02630264
• Lead Sponsor: Guangzhou Double Bioproducts Co., Ltd

Brief Summary

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.

Detailed Description

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.

The OS of the E10A group was relatively prolonged in different subgroups compared with the controls (e.g., 13.37 months versus 9.67 months in the HNSCC patients, 13.03 months versus 10.50 months in those who had received prior treatment; Figure 1), but these results did not translate into significantly superior survival.

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2013-12-26
• Status Verified: 2015-12
• Study First Submitted QC: 2015-12-10
• Last Update Submitted: 2015-12-10
• Study First Posted: 2015-12-15
• Last Update Posted: 2015-12-15
• Primary Completion: 2016-06
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 540

Inclusion Criteria

1. Patients older than 18 years with histologically or cytologically proven locoregionally advanced or metastatic HNSCC (excluding NPC) not suitable for operation or radiotherapy
2. A life expectancy≧12 weeks.
3. 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,
4. Not received chemotherapy, radiotherapy, or biotherapy within 4 weeks.
5. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-2.
6. Adequate bone marrow,renal, and liver functions.

Exclusion Criteria

1. Known allergies to the study drug.
2. The presence of important blood vessels/nerves or ulceration in the target lesion not suitable for injection.
3. Tumor relapses within 6 months after paclitaxel chemotherapy.
4. Severe coagulation disorders or bleeding tendency.
5. Severe uncontrolled medical conditions.
6. Recent history of myocardial infarction acute infection, pregnancy or lactation, or symptomatic brain metastases
7. A history of corticosteroids or immunosuppressives use within four weeks of study entry
8. Received any chemotherapy or radiotherapy within four weeks of study entry

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemotherapy	Paclitaxel injection	Chemotherapy-alone group (180 subjects): 1. Paclitaxel Injection 160mg/m2 on day 1 2. Cisplatin Injection 25mg/m2 on day 1, 2, and 3. Repeat every 21 days
Combination therapy	Cisplatin injection	E10A+chemotherapy group (360 subjects): 1. E10A (Endostatins) of 1.0×1012VP on day 1 and 6 2. Paclitaxel Injection 160mg/m2 on day 3 3. Cisplatin Injection 25mg/m2 on day 3, 4, and 5. Repeat every 21 days.
Combination therapy	Paclitaxel injection	E10A+chemotherapy group (360 subjects): 1. E10A (Endostatins) of 1.0×1012VP on day 1 and 6 2. Paclitaxel Injection 160mg/m2 on day 3 3. Cisplatin Injection 25mg/m2 on day 3, 4, and 5. Repeat every 21 days.
Chemotherapy	Cisplatin injection	Chemotherapy-alone group (180 subjects): 1. Paclitaxel Injection 160mg/m2 on day 1 2. Cisplatin Injection 25mg/m2 on day 1, 2, and 3. Repeat every 21 days
Combination therapy	Endostatins	E10A+chemotherapy group (360 subjects): 1. E10A (Endostatins) of 1.0×1012VP on day 1 and 6 2. Paclitaxel Injection 160mg/m2 on day 3 3. Cisplatin Injection 25mg/m2 on day 3, 4, and 5. Repeat every 21 days.

Primary Outcome Measures

Name	Time	Method
Time to progression	Up to 24 weeks	Time to progression is defined as the time from randomization until objective tumor progression as verified for the first time

Secondary Outcome Measures

Name	Time	Method
Change in Overall response rate (CR+PR)	Up to 24 weeks, from date of randomization until the date of first documented progression	the end of every 2 treatment cycles (each cycle is 21 days), and every 3 months during follow-up until disease progression. 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.
Chang in disease control rate (CR+PR+SD)	Up to 24 weeks, From date of randomization until the date of first documented progression	the end of every 2 treatment cycles(each cycle is 21 days), and every 3 months during follow-up until disease progression.The CR or PR patients were reconfirmed
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	All adverse events were recorded regardless of their relevance to E10A
Overall survival	Up to 24 month, through study completion	from cycle 2 to cycle 4 and calculated the survival during follow-up

Trial Locations

Locations (1)

Guangzhou DB; 🇨🇳 Gaungzhou, Guangdong, China