Clinical Trial: Clinical Study of EBV-LMP1 Targeted DNAzyme to Treat Nasopharyngeal Carcinoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I/II Study of EBV-LMP1 Targeted DNAzyme in Nasopharyngeal Carcinoma

Brief Summary: The purpose of this study is to determine whether an EBV-LMP1 targeted DNAzyme is effective in radiosensitization of nasopharyngeal carcinoma in combination with standard radiation therapy.

Detailed Summary:

INTRODUCTION Nasopharyngeal carcinoma (NPC) is a serious health problems worldwide, particularly in the southern Chinese population, with an incidence rate ranging from 15 to 50 per 100 000. NPC is an epithelial malignancy with a striking racial and geographic distribution differences. High incidence rates are observed in the southeast Chinese population, and similar rates have been reported in these people wherever they have migrated, including Singapore, Taiwan, and Hong Kong. This incidence is almost 100 fold higher than in white populations. The most unique feature of NPC is its almost universal association with the infection of Epstein-Barr virus (EBV), which is the first human virus identified to be involved in the pathogenesis of several malignancies and has a particularly close association with NPC, as EBV genome can be detected in virtually all NPC cells. While radiotherapy has been the first-line treatments for NPC, radio-resistance remains a significant clinical issue for the NPC radiotherapy. Thus, there is unmet medical needs to discover and develop novel radiosensitizers for NPC therapy.

EBV infection in NPC is classified as type II latent infection in which only EBV nuclear antigen-1(EBNA-1), latent membrane protein-1(LMP1), LMP2, and EBV early RNA (EBER) expressions can be detected. Among these proteins, LMP1 is thought to play a key role in the pathogenesis of NPC. As a 60kD integral membrane protein, LMP1 functions as a constitutively active tumor necrosis factor receptor (TNFR), and contributes to multiple aspects of NPC through activating a number of signaling pathways including nuclear factor NF-κB, activator protein-1(AP-1), and Janus kinase/signal transducer and activator of transcription(JAK/STAT). Activation of NF-kB or AP-1 by LMP1 has been linked to the upregulation of some cellular proteins and inhibition of apoptosis. Depending on the cel
Sponsor: Xiangya Hospital of Central South University

Current Primary Outcome: Tumor regression rate measured by MRI [ Time Frame: Two years ]

Tumor growth is measured using MRI weekly from week 1 to week 7, followed by six-monthly measures until week 104.


Original Primary Outcome: Same as current

Current Secondary Outcome: Tumor vasculature permeability and EBV DNA copies [ Time Frame: Two years ]

Tumor vasculature permeability is measured using DCE-MRI from week 1 to week 52. EBV DNA copies are measured monthly up to 24 months.EBV cpoies are measured by quantitative PCR.


Original Secondary Outcome: Same as current

Information By: Xiangya Hospital of Central South University

Dates:
Date Received: October 4, 2011
Date Started: May 2009
Date Completion:
Last Updated: October 6, 2011
Last Verified: October 2011