Trial of E10A in Head and Neck Cancer

NCT ID: NCT00634595

Last Updated: 2010-07-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2010-12-31

Brief 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.

Conditions

Head and Neck Squamous Carcinoma; Nasopharyngeal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

E10A combined with Cisplatin and Paclitaxel

Group Type: EXPERIMENTAL

E10A

Intervention Type: DRUG

E10A 1\*10(12)VP, intratumoral injection, d1 d8, repeat every 3 weeks for 4 cycles

Cisplatin

Intervention Type: DRUG

25 mg/m2/d ivd d3 d4 d5, repeat every 3 weeks for 4 cycles.

Paclitaxel

Intervention Type: DRUG

160 mg/m2 ivd d3, repeat every 3 weeks for 4 cycles.

B

Cisplatin and Paclitaxel

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

25 mg/m2/d ivd d3 d4 d5, repeat every 3 weeks for 4 cycles.

Paclitaxel

Intervention Type: DRUG

160 mg/m2 ivd d3, repeat every 3 weeks for 4 cycles.

Interventions

E10A

E10A 1\*10(12)VP, intratumoral injection, d1 d8, repeat every 3 weeks for 4 cycles

Intervention Type: DRUG

Cisplatin

25 mg/m2/d ivd d3 d4 d5, repeat every 3 weeks for 4 cycles.

Intervention Type: DRUG

Paclitaxel

160 mg/m2 ivd d3, repeat every 3 weeks for 4 cycles.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Doublle Bioproduct Inc

INDUSTRY

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Cancer center, Sun Yat-sen University

Principal Investigators

Wenqi Jiang

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Cancer center, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xubin Lin, MD, PhD

Role: CONTACT

linxubin@mail.sysu.edu.cn

86-20-87343355

Facility Contacts

Xubin Lin, MD, PhD

Role: primary

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. doi: 10.4161/cbt.6.5.4004. Epub 2007 Feb 13.

Reference Type: BACKGROUND

PMID: 17426445 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24662947 (View on PubMed)

Other Identifiers

TG0717E10A

Identifier Type: -

Identifier Source: org_study_id