Brief Summary

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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"

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.

• Study Type: Interventional
• Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Study Primary Completion Date: December 2010

Interventions Used in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • E10A combined with Cisplatin and Paclitaxel
• Active Comparator: B
  • Cisplatin and Paclitaxel

Outcome Measures for this Clinical Trial

Primary Measures

• tumor response confirmed by CT or MRI
  • Time Frame: 3 months
    Safety Issue?: No

Secondary Measures

• NCI toxicity criteria (CIC 3.0)
  • Time Frame: 3 months
    Safety Issue?: Yes

Criteria for Participation in this Clinical Trial

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

• Lead Sponsor
  • Sun Yat-sen University
• Collaborator
  • Doublle Bioproduct Inc
• Provider of Information About this Clinical Study
  • Wenqi Jiang, Professor, Cancer center, Sun Yat-sen University
• Overall Official(s)
  • Wenqi Jiang, Principal Investigator, Sun Yat-sen University
• Overall Contact(s)
  • Xubin Lin, MD, PhD, 86-20-87343355, linxubin@mail.sysu.edu.cn

References

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.