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

NCT01449942 | Completed Phase 1 DMC

• 1 other identifier: CSU-863-DZ
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal carcinoma; EBV; LMP1

Outcome Measures

Primary Outcomes (1)

• Tumor regression rate measured by MRI

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

  Two years

Secondary Outcomes (1)

• Tumor vasculature permeability and EBV DNA copies

  Two years

Study Arms (2)

DZ1

EXPERIMENTAL

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

Biological: DNAzyme targeting EBV-LMP1 (DZ1); Other: Saline

Saline

PLACEBO COMPARATOR

Placebo group receives saline injection in combination with radiation therapy.

Biological: DNAzyme targeting EBV-LMP1 (DZ1); Other: Saline

Interventions

DNAzyme targeting EBV-LMP1 (DZ1) BIOLOGICAL

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.

DZ1; Saline

Saline OTHER

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.

DZ1; Saline

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Xiangya Hospital of Central South University: lead

Study Sites (1)

XiangYa Hospital, Central South University

Changsha, Hunan, 410078, China

Location

Related Publications (9)

• 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. doi: 10.3390/molecules15096127.

  PMID: 20877211 BACKGROUND

• 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. doi: 10.1016/j.canlet.2008.02.019. Epub 2008 Mar 18.

  PMID: 18353539 BACKGROUND

• 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. doi: 10.1038/sj.cgt.7700833.

  PMID: 15803142 BACKGROUND

• 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. doi: 10.1089/108729002761381276.

  PMID: 12477279 BACKGROUND

• 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.

  PMID: 10977866 BACKGROUND

• 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. doi: 10.1038/8658.

  PMID: 10331809 BACKGROUND

• Cao Y, DePinho RA, Ernst M, Vousden K. Cancer research: past, present and future. Nat Rev Cancer. 2011 Sep 15;11(10):749-54. doi: 10.1038/nrc3138.

  PMID: 21918542 BACKGROUND

• 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.

  PMID: 17601372 BACKGROUND

• Liao WH, Yang LF, Liu XY, Zhou GF, Jiang WZ, Hou BL, Sun LQ, Cao Y, Wang XY. DCE-MRI assessment of the effect of Epstein-Barr virus-encoded latent membrane protein-1 targeted DNAzyme on tumor vasculature in patients with nasopharyngeal carcinomas. BMC Cancer. 2014 Nov 18;14:835. doi: 10.1186/1471-2407-14-835.

  PMID: 25407966 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Lun-Quan Sun, PhD

  Xiangya Hospital, Central South University, Changsha, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for Molecular Medicine, Central South University

Study Record Dates

• First Submitted: October 4, 2011
• First Posted: October 10, 2011
• Study Start: May 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: September 1, 2011
• Last Updated: October 10, 2011

Record last verified: 2011-10

Locations

CN (1)