Clinical Study of EBV-LMP1 Targeted DNAzyme to Treat Nasopharyngeal Carcinoma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Nasopharyngeal Carcinoma	Biological: DNAzyme targeting EBV-LMP1 (DZ1) Other: Saline	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Phase I/II Study of EBV-LMP1 Targeted DNAzyme in Nasopharyngeal Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Xiangya Hospital of Central South University:

Primary Outcome Measures:

Tumor regression rate measured by MRI [ Time Frame: Two years ] [ Designated as safety issue: Yes ]
Tumor growth is measured using MRI weekly from week 1 to week 7, followed by six-monthly measures until week 104.

Secondary Outcome Measures:

Tumor vasculature permeability and EBV DNA copies [ Time Frame: Two years ] [ Designated as safety issue: Yes ]
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.

Enrollment:	40
Study Start Date:	May 2009
Study Completion Date:	September 2011
Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: DZ1 DZ1 group receives DZ1 intratumoral injection in combination with radiation therapy.	Biological: DNAzyme targeting EBV-LMP1 (DZ1) DZ1 in saline is administrated by intratumoral injection two hours prior to radiation therapy from week 1 to week 7 on Monday and Thursday. Dosage for each injection is 12 mg in 0.1 mL (200 micrograms per kilogram body weight. The radical radiotherapy is given to patients 5 times per week with 2 Gy of each treatment. The entire procedure lasts seven weeks. Other: Saline 0.1 mL of saline is administrated by intratumoral injection two hours prior to radiation therapy from week 1 to week 7 on Monday and Thursday. The radical radiotherapy is given to patients 5 times per week with 2 Gy of each treatment. The entire procedure lasts seven weeks.
Placebo Comparator: Saline Placebo group receives saline injection in combination with radiation therapy.	Biological: DNAzyme targeting EBV-LMP1 (DZ1) DZ1 in saline is administrated by intratumoral injection two hours prior to radiation therapy from week 1 to week 7 on Monday and Thursday. Dosage for each injection is 12 mg in 0.1 mL (200 micrograms per kilogram body weight. The radical radiotherapy is given to patients 5 times per week with 2 Gy of each treatment. The entire procedure lasts seven weeks. Other: Saline 0.1 mL of saline is administrated by intratumoral injection two hours prior to radiation therapy from week 1 to week 7 on Monday and Thursday. The radical radiotherapy is given to patients 5 times per week with 2 Gy of each treatment. The entire procedure lasts seven weeks.

Arms

Assigned Interventions

Experimental: DZ1

DZ1 group receives DZ1 intratumoral injection in combination with radiation therapy.

Biological: DNAzyme targeting EBV-LMP1 (DZ1)

DZ1 in saline is administrated by intratumoral injection two hours prior to radiation therapy from week 1 to week 7 on Monday and Thursday. Dosage for each injection is 12 mg in 0.1 mL (200 micrograms per kilogram body weight.

The radical radiotherapy is given to patients 5 times per week with 2 Gy of each treatment. The entire procedure lasts seven weeks.

Other: Saline

0.1 mL of saline is administrated by intratumoral injection two hours prior to radiation therapy from week 1 to week 7 on Monday and Thursday.

The radical radiotherapy is given to patients 5 times per week with 2 Gy of each treatment. The entire procedure lasts seven weeks.

Placebo Comparator: Saline

Placebo group receives saline injection in combination with radiation therapy.

Biological: DNAzyme targeting EBV-LMP1 (DZ1)

DZ1 in saline is administrated by intratumoral injection two hours prior to radiation therapy from week 1 to week 7 on Monday and Thursday. Dosage for each injection is 12 mg in 0.1 mL (200 micrograms per kilogram body weight.

The radical radiotherapy is given to patients 5 times per week with 2 Gy of each treatment. The entire procedure lasts seven weeks.

Other: Saline

0.1 mL of saline is administrated by intratumoral injection two hours prior to radiation therapy from week 1 to week 7 on Monday and Thursday.

The radical radiotherapy is given to patients 5 times per week with 2 Gy of each treatment. The entire procedure lasts seven weeks.

Show Detailed Description

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Clinical diagnosis of nasopharyngeal squamous carcinoma
EBV-LMP1 positive
Signed Informed Consent Form

Exclusion Criteria:

Abnormal laboratory results within 45 days prior to study entry
Participation in any study involving an experimental drug or an experimental medical device in 30 days prior to study entry
Current pregnancy
Inability to provide informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01449942

Locations

China, Hunan
XiangYa Hospital, Central South University
Changsha, Hunan, China, 410078

Sponsors and Collaborators

Xiangya Hospital of Central South University

Investigators

Principal Investigator:

Lun-Quan Sun, PhD

Xiangya Hospital, Central South University, Changsha, China

More Information

Publications:

Yang L, Lu Z, Ma X, Cao Y, Sun LQ. A therapeutic approach to nasopharyngeal carcinomas by DNAzymes targeting EBV LMP-1 gene. Molecules. 2010 Sep 1;15(9):6127-39. Review.

Lu ZX, Ma XQ, Yang LF, Wang ZL, Zeng L, Li ZJ, Li XN, Tang M, Yi W, Gong JP, Sun LQ, Cao Y. DNAzymes targeted to EBV-encoded latent membrane protein-1 induce apoptosis and enhance radiosensitivity in nasopharyngeal carcinoma. Cancer Lett. 2008 Jul 8;265(2):226-38. Epub 2008 Mar 18.

Lu ZX, Ye M, Yan GR, Li Q, Tang M, Lee LM, Sun LQ, Cao Y. Effect of EBV LMP1 targeted DNAzymes on cell proliferation and apoptosis. Cancer Gene Ther. 2005 Jul;12(7):647-54.

Dass CR, Saravolac EG, Li Y, Sun LQ. Cellular uptake, distribution, and stability of 10-23 deoxyribozymes. Antisense Nucleic Acid Drug Dev. 2002 Oct;12(5):289-99.

Sun LQ, Cairns MJ, Saravolac EG, Baker A, Gerlach WL. Catalytic nucleic acids: from lab to applications. Pharmacol Rev. 2000 Sep;52(3):325-47. Review.

Cairns MJ, Hopkins TM, Witherington C, Wang L, Sun LQ. Target site selection for an RNA-cleaving catalytic DNA. Nat Biotechnol. 1999 May;17(5):480-6.

Cao Y, Depinho RA, Ernst M, Vousden K. Cancer research: past, present and future. Nat Rev Cancer. 2011 Sep 15;11(10):749-54.

Zheng H, Li LL, Hu DS, Deng XY, Cao Y. Role of Epstein-Barr virus encoded latent membrane protein 1 in the carcinogenesis of nasopharyngeal carcinoma. Cell Mol Immunol. 2007 Jun;4(3):185-96. Review.

Responsible Party:	Sun lunquan, Director, Center for Molecular Medicine, Central South University, Xiangya Hospital of Central South University
ClinicalTrials.gov Identifier:	NCT01449942 History of Changes
Other Study ID Numbers:	CSU-863-DZ
Study First Received:	October 4, 2011
Last Updated:	October 6, 2011
Health Authority:	China: Ministry of Science and Technology

Keywords provided by Xiangya Hospital of Central South University:

Nasopharyngeal carcinoma
EBV
LMP1

Additional relevant MeSH terms:

Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms

Neoplasms by Site
Nasopharyngeal Diseases
Carcinoma
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on May 21, 2013

Clinical Study of EBV-LMP1 Targeted DNAzyme to Treat Nasopharyngeal Carcinoma (NPC-DZ)