Trial of E10A in Head and Neck Cancer

Nasopharyngeal Carcinoma Clinical Trial

Official title:

A Randomized Phase II Clinical Trial of an Adenovirus-mediated Endostatin Gene (E10A) Combined With Cisplatin and Paclitaxel in Patients With Head and Neck Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00634595
• Other study ID #: TG0717E10A
• Status: Recruiting
• Phase: Phase 2
• First received: March 5, 2008
• Last updated: July 26, 2010
• Start date: March 2008
• Est. completion date: December 2010

Study information

• Verified date: July 2010
• Source: Sun Yat-sen University
• Contact: Xubin Lin, MD, PhD
• Phone: 86-20-87343355
• Email: linxubin[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Angiogenesis, the formation of new blood vessel from existing vessels, is essential for tumor growth and metastasis. Antiangiogenic therapies inhibit the growth of genetically stable endothelial cells, and most tumors should starve to death with little acquired resistance. Endostatin has been shown to block endothelial cell proliferation, survival, and migration. Antitumor activity of endostatin protein has been demonstrated in various murine and human tumors in animal model studies without any detectable toxicity. Endostatin gene therapy could directly express the highly bioactive protein in vivo by means of the mechanism of eukaryotic expression system as post-translational modification and folding, as well as overcoming the challenge of the long-term storage and the cumbersome daily administration of endostatin protein.

E10A is a replication-deficient recombinant adenovirus containing a wild-type human endostatin transgene constructed from serotype 5 adenovirus (Ad5). Preclinical studies demonstrated that intratumoral injection of E10A provided significant tumor growth inhibition and sustained elevation of endostatin in blood and tumor tissue in hepatocellular carcinoma, nasopharyngeal carcinoma, and tongue cancer animal models. A Phase I clinical trial of E10A we conducted showed that repetitive intratumoral injection of E10A resulted in a small and sustained elevation of endostatin in blood and had a mild antitumor activities with very limited toxicity. The major toxicity was transient and manageable fever. A randomized Phase III trial in nonsmall-cell lung cancer showed endostatin improved response rate and time to tumor progression in combination to chemotherapy. Therefore, we designed a randomized phase II trial to explore the safety and effectiveness of E10A combined with chemotherapy in the treatment of patients with head and neck cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 116
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• histologically or cytologically confirmed recurrent or metastatic head and neck squamous carcinoma or nasopharyngeal carcinoma

• the tumor was amenable to direct injection and measurement ( > 2 cm)

• an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

• a life expectancy over three months

• the absence of serious medical or psychiatric disorders

• serum creatinine < 1.5 mg/dL; WBC count >3,000/mm3, platelet count > 80,000/mm3, hemoglobin > 8 g/dL; total bilirubin value < 1.5 times the upper limit of normal [ULN], ALT level < 2.5 times ULN, AST < 2.5 times ULN.

Exclusion Criteria:

• pregnant or breast feeding

• a history of brain metastases or a primary brain tumor

• a history of hemorrhagic diathesis

• a history of corticosteroids or immunosuppressives use within four weeks of study entry

• a history of immune deficiency disorder or organ transplant

• has evidence of active adenovirus infection or uncontrolled infection

• received any chemotherapy or radiotherapy within four weeks of study entry

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Head and Neck Squamous Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• E10A
E10A 1*10(12)VP, intratumoral injection, d1 d8, repeat every 3 weeks for 4 cycles
• Cisplatin
25 mg/m2/d ivd d3 d4 d5, repeat every 3 weeks for 4 cycles.
• Paclitaxel
160 mg/m2 ivd d3, repeat every 3 weeks for 4 cycles.

Locations

Country	Name	City	State
China	Cancer center, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	Doublle Bioproduct Inc

Country where clinical trial is conducted

China, 

References & Publications (1)

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. Epub 2007 Feb 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	tumor response confirmed by CT or MRI		3 months	No
Secondary	NCI toxicity criteria (CIC 3.0)		3 months	Yes