Clinical trial NCT00634595: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Head and Neck Squamous Carcinoma
Nasopharyngeal Carcinoma
Keywords: clinical trial
randomized
Endostatin
gene therapy
head and neck cancer
head and neck squamous carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Doublle Bioproduct Inc
First posted: 2008-03-13
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: tumor response confirmed by CT or MRI
timeFrame: 3 months
Secondary outcomes:
measure: NCI toxicity criteria (CIC 3.0)
timeFrame: 3 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Cancer center, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Wenqi Jiang
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.