Study of Cytolytic Viral Activation Therapy (CVAT) for Recurrent/Metastatic Nasopharyngeal Carcinoma

Summary

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus(EBV) related malignancy and is an endemic disease in Southeast Asian countries. EBV had been identified as a therapeutic target in some EBV related cancer such as lymphoma and NPC. In cancer cell, EBV was in latent phase and expressed 8-11 genes for maintaining EBV proliferation. After switching to lytic phase, almost all the EBV encoding genes were expressed including thymidine kinase (TK) and some highly immunogenetic genes. These latent-lytic phase swifter included DNA methyltransferase inhibitors, various histone deacetylase (HDAC) inhibitors, radiotherapy and chemotherapy. Recently, combined chemotherapy and viral lytic therapy, cytolytic viral activation therapy (CVAT) had been shown some promising result in pilot study of NPC. In our patient derived xenograft (PDX) animal model drug sensitivity screening, gemcitabine (GEM) was shown to be the most effective drug. Furthermore, CVAT with GEM + Valproic acid (VPA) + ganciclovir (GCV) maintaining chemotherapy may benefit but reduce chemotherapy related side effect and prolonging treatment response duration. The following phase I clinical trial will be proposed to test the optimal combination of these drugs.

1. Number of patients: total 18 patients are needed
2. Inclusion criteria:(1) used as 2nd line regimen in recurrence/metastasis NPC patients with tissue proved of World Health Organization (WHO) type II or type III.(2) Performance status: eastern cooperative oncology group performance status (ECOG PS) ≤2.
3. Chemotherapy regimen: Gemcitabine (GEM, TTY) + Valproic acid (VPA, generic medicine) for viral activation + Valganciclovir (VGC, Roche) for antiviral medication
4. This treatment cycle of 28 days was repeated maximum 6 times. (Q4wks/cycle, max: 6 cycles)
5. Dosage:

(1) GEM: 600, 800, 1000, 1250 mg/m\^2, D1 \& D8, intravenously. (2) VPA 12.5 mg/kg/day D1\~14, per os. (3) VGC (2-3) x 450 mg/day D9\~15, per os. 6. Objectives:

1. primary: to find the best combination of these 3 drugs in recurrent/metastatic NPC patients.
2. second: to evaluate the response and disease control rate in this pilot study.

Key words: NPC, cytolytic viral activation therapy, gemcitabine, valproic acid, ganciclovir.

Conditions

• Nasopharyngeal Carcinoma

Interventions

DRUG

Gemcitabine

Gemcitabine will be administrated 600\~1250 mg/m\^2 intravenously according to the body surface area at day 1 and day 8 in a 28 day-treatment cycle. The treatment cycle of 28 days will be repeated maximum 6 times. The first dose level of gemcitabine will be started at 800 mg/m\^2. If no subject suffered the dose limit toxicity, 1000 mg/m\^2 and even 1250 mg/m\^2 will be started by order. If subjects suffered the dose limit toxicity in 800 mg/m\^2, the 600 mg/m\^2 will be started.

DRUG

Valproic acid

Valproic acid will be administrated orally by the fixed dose 12.5 mg/kg/day according to instructions from day 1 to day 14 in one treatment cycle. The treatment cycle of 28 days will be repeated maximum 6 times.

DRUG

Valganciclovir

Valganciclovir will be administrated orally by the fixed dose 1350 mg/day (creatinine clearance rate ≥ 60 mL/min) or 900 mg/day (creatinine clearance rate ≥ 40 mL/min and \< 60 mL/min) from day 9 to day 15 in one treatment cycle. The treatment cycle of 28 days will be repeated maximum 6 times.

Sponsors & Collaborators

• TTY Biopharm

  collaborator INDUSTRY

• Chang Gung Memorial Hospital

  lead OTHER

Principal Investigators

• Cheng-Lung Hsu, Physican · Chang Gung Memorial Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

20 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-05-31

Primary Completion

2017-06-30

Countries

• Taiwan

Study Locations