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

• Status: Unknown status
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Chang Gung Memorial Hospital
• Collaborator: TTY Biopharm
• Treatments: Ganciclovir; Gemcitabine; Valganciclovir; Valproic Acid

Criteria

Inclusion Criteria:

1. Have the ability to understand and willingness to sign a written informed consent document

2. Identified as recurrent nasopharyngeal carcinoma or distant metastases of male or female subjects who had failed in 1st line therapy including radiotherapy, not suitable for radiotherapy or unwilling to receive radiotherapy, 1st line chemotherapy excluding gemcitabine, and no curative treatment options

3. Biopsy confirmed belong to World Health Organization classification of nasopharyngeal carcinoma type II or type III

4. Men and women between aged 20 to 80 years of age; female patients with childbearing potential will routinely consult obstetric doctor for contraception and need to have contraception at least 6 months after finished this trial

5. Adequate internal organs including liver, kidney and bone marrow function

• white blood cell count of >3,000/µL; platelet count of ≥100,000/µL; absolute neutrophil count >1,500/µL

• total bilirubin <2.0 mg/dL, aspartate aminotransferase (AST), alanine transaminase(ALT) <2.5x upper limit of normal range (ULN)

• serum creatinine <2.0 mg/dL

6. The daily performance status ECOG ≤ 2 points

Exclusion Criteria:

1. Pregnancy or breast-feeding women, and plans within six months of pregnancy

2. Contraindication to Gemmis injection, Depakine gastro-resistant tablet, and Valcyte film-coated tablets, including:

• Allergy to Gemmis injection, Depakine gastro-resistant tablet, Valcyte film-coated tablets, and other similar drugs

• Patients with hepatic B or C, patients with human immunodeficiency virus, or viral related disease receiving anti-viral treatment

• Acute or chronic hepatitis not related to NPC with liver metastasis

• Using drugs which ineligible combination with valproic acid, including mefloquine, St.-John's-Wort, lamotrigine, Topiramate, quetiapine, cyclosporin, hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine phenobarbital, primidone, rifampin), enzyme inhibitors (e.g., felbamate), aspirin, cimetidine, erythromycin, carbapenem (e.g., Panipenem, Aztreonam, Imipenem, Meropenem), diazepam, ethosuximide, lamotrigine, phenytoin, nimodipine

3. With insomnia, anxiety or spiritual concerns, or are receiving mental illness treatment

4. Has been diagnosed with a second cancer, except to basal cell carcinoma

5. Patients unsuitable to this trial, including:

• Patients with significant disease

• PI evaluated with high risk group patients

• Patients not recovered from previous anti-cancer treatment

• Recent major surgery

6. Patients with creatinine clearance rate <40 ml/min