Trial of E10A in Head and Neck Cancer

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 Overview

• Status: Unknown
• Conditions: Nasopharyngeal Carcinoma; Head and Neck Squamous Carcinoma
• Intervention / Treatment: Drug: E10A; Drug: Cisplatin; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Anticipated): 116
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xubin Lin, MD, PhD; Phone Number: 86-20-87343355; Email: linxubin@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer Center, Sun Yat-sen University
      • Contact: Xubin Lin, MD, PhD; Email: linxubin@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; E10A combined with Cisplatin and Paclitaxel	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.
Active Comparator: B; Cisplatin and Paclitaxel	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
tumor response confirmed by CT or MRI	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
NCI toxicity criteria (CIC 3.0)	3 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Doublle Bioproduct Inc
• Investigators: Principal Investigator: Wenqi Jiang, Sun Yat-sen University

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Anticipated): December 1, 2010
• Study Completion (Anticipated): December 1, 2010

Study Registration Dates

• First Submitted: March 5, 2008
• First Submitted That Met QC Criteria: March 5, 2008
• First Posted (Estimate): March 13, 2008

Study Record Updates

• Last Update Posted (Estimate): July 28, 2010
• Last Update Submitted That Met QC Criteria: July 26, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Keywords: clinical trial; gene therapy; head and neck cancer; randomized; head and neck squamous carcinoma; Endostatin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Squamous Cell; Nasopharyngeal Neoplasms; Head and Neck Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Carcinoma, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin
• Other Study ID Numbers: TG0717E10A