Trial of E10A in Head and Neck Cancer

• ClinicalTrials.gov Identifier: NCT00634595
• Recruitment Status: Unknown
• First Posted: March 13, 2008
• Last Update Posted: July 28, 2010
• Sponsor: Sun Yat-sen University
• Collaborator: Doublle Bioproduct Inc
• Information provided by: Sun Yat-sen University

Tracking Information

• First Submitted Date: March 5, 2008
• First Posted Date: March 13, 2008
• Last Update Posted Date: July 28, 2010
• Study Start Date: March 2008
• Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 5, 2008): tumor response confirmed by CT or MRI [ Time Frame: 3 months ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: March 5, 2008): NCI toxicity criteria (CIC 3.0) [ Time Frame: 3 months ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of E10A in Head and Neck Cancer
• 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Head and Neck Squamous Carcinoma
• Nasopharyngeal Carcinoma

Intervention

• 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.

Study Arms

• Experimental: A
  E10A combined with Cisplatin and Paclitaxel
  Interventions:

  • Drug: E10A
  • Drug: Cisplatin
  • Drug: Paclitaxel
• Active Comparator: B
  Cisplatin and Paclitaxel
  Interventions:

  • Drug: Cisplatin
  • Drug: Paclitaxel

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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 5, 2008): 116
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2010
• Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT00634595
• Other Study ID Numbers: TG0717E10A
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Wenqi Jiang, Professor, Cancer center, Sun Yat-sen University
• Original Responsible Party: Same as current
• Current Study Sponsor: Sun Yat-sen University
• Original Study Sponsor: Same as current
• Collaborators: Doublle Bioproduct Inc

Investigators

• Principal Investigator: Wenqi Jiang; Sun Yat-sen University

• PRS Account: Sun Yat-sen University
• Verification Date: July 2010