Clinical trial NCT02630264: E10A for the Treatment of Squamous Cell Carcinoma of the Head and Neck
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Head and Neck Neoplasms
Keywords: clinical trial
Recombinant Human Endostatin Adenovirus
randomized
Lead sponsor: Guangzhou Double Bioproducts Co., Ltd
Sponsor class: INDUSTRY
First posted: 2015-12-15
Enrollment: 540
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to progression
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Change in Overall response rate (CR+PR)
timeFrame: Up to 24 weeks, from date of randomization until the date of first documented progression
measure: Chang in disease control rate (CR+PR+SD)
timeFrame: Up to 24 weeks, From date of randomization until the date of first documented progression
measure: Incidence of Treatment-Emergent Adverse Events (Safety and tolerability)
timeFrame: Up to 32 weeks, from date of randomization until the date of first documented progression or date
measure: Overall survival
timeFrame: Up to 24 month, through study completion
Other outcomes:
Locations:
city: Gaungzhou
country: China
facility: Guangzhou DB
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Huiqiang Huang, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ye W, Liu R, Pan C, Jiang W, Zhang L, Guan Z, Wu J, Ying X, Li L, Li S, Tan W, Zeng M, Kang T, Liu Q, Thomas GR, Huang M, Deng W, Huang W. Multicenter randomized phase 2 clinical trial of a recombinant human endostatin adenovirus in patients with advanced head and neck carcinoma. Mol Ther. 2014 Jun;22(6):1221-1229. doi: 10.1038/mt.2014.53. Epub 2014 Mar 25.
citation: Lin X, Huang H, Li S, Li H, Li Y, Cao Y, Zhang D, Xia Y, Guo Y, Huang W, Jiang W. A phase I clinical trial of an adenovirus-mediated endostatin gene (E10A) in patients with solid tumors. Cancer Biol Ther. 2007 May;6(5):648-53. doi: 10.4161/cbt.6.5.4004. Epub 2007 Feb 13.