NCT00634595

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
116

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Mar 2008

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2008

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

March 5, 2008

Completed
8 days until next milestone

First Posted

Study publicly available on registry

March 13, 2008

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2010

Completed
Last Updated

July 28, 2010

Status Verified

July 1, 2010

Enrollment Period

2.8 years

First QC Date

March 5, 2008

Last Update Submit

July 26, 2010

Conditions

Keywords

clinical trialrandomizedEndostatingene therapyhead and neck cancerhead and neck squamous carcinoma

Outcome Measures

Primary Outcomes (1)

  • tumor response confirmed by CT or MRI

    3 months

Secondary Outcomes (1)

  • NCI toxicity criteria (CIC 3.0)

    3 months

Study Arms (2)

A

EXPERIMENTAL

E10A combined with Cisplatin and Paclitaxel

Drug: E10ADrug: CisplatinDrug: Paclitaxel

B

ACTIVE COMPARATOR

Cisplatin and Paclitaxel

Drug: CisplatinDrug: Paclitaxel

Interventions

E10ADRUG

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

A

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

AB

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

AB

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cancer center, Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (2)

  • 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.

    PMID: 17426445BACKGROUND
  • 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.

MeSH Terms

Conditions

Nasopharyngeal CarcinomaHead and Neck Neoplasms

Interventions

CisplatinPaclitaxel

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNasopharyngeal NeoplasmsPharyngeal NeoplasmsOtorhinolaryngologic NeoplasmsNeoplasms by SiteNasopharyngeal DiseasesPharyngeal DiseasesStomatognathic DiseasesOtorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Chlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Study Officials

  • Wenqi Jiang

    Sun Yat-sen University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

March 5, 2008

First Posted

March 13, 2008

Study Start

March 1, 2008

Primary Completion

December 1, 2010

Study Completion

December 1, 2010

Last Updated

July 28, 2010

Record last verified: 2010-07

Locations