A Trial of Adjuvant Chemotherapy in Nasopharyngeal Carcinoma Patients With Residual Epstein-Barr Virus (EBV) DNA Following Radiotherapy

Study Overview
=================
Brief Summary
-----------------
The purpose of this trial is to study the benefit of adjuvant chemotherapy using gemcitabine and cisplatin in high risk NPC patients with residual EBV DNA following primary radiotherapy with or without concurrent cisplatin.

Detailed Description
-----------------
The standard treatment for nasopharynx cancer is a course of radiotherapy with or without concurrent chemotherapy. This will cure about 80% of patients. For the 20% who developed recurrence or metastases, the prognosis is poor. Elevated EBV-DNA in plasma at end of radiotherapy has been shown to predict disease recurrence and may be a marker of subclinical residual disease. This study aims to test whether adjuvant treatment with 6 cycles of a modern chemotherapy regimen (gemcitabine and cisplatin combination) can improve the survival of these high risk patients of nasopharynx cancer who have elevated EBV-DNA after completion of their radiotherapy.

Official Title
-----------------
A Multi-center Prospective Randomized Phase III Trial to Determine the Benefit of Adjuvant Chemotherapy Using Gemcitabine and Cisplatin in Nasopharyngeal Carcinoma Patients With Residual EBV DNA Following Primary Radiotherapy With or Without Concurrent Cisplatin

Conditions
-----------------
Nasopharyngeal Cancer

Intervention / Treatment
-----------------
* Drug: Adjuvant chemotherapy (gemcitabine and cisplatin)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have given written informed consent, prior to pre-study screening, with the understanding that consent may be withdrawn at any time without prejudice. A histological diagnosis of nasopharyngeal cancer (NPC) must have been established at some time and the investigator must review and confirm the diagnosis prior to randomization. Loco-regional advanced NPC UICC/AJCC Stages IIB, III, IVA or IVB. No evidence of distant metastases in the staging work up at diagnosis. Must have detectable plasma EBV-DNA (> 0 copies/ml) at 6-8 weeks after completion of primary RT or chemo-RT No clinical evidence of persistent loco-regional disease after primary treatment Performance status of ECOG grade 0 or 1. Patients must have adequate organ and marrow function as defined below: leukocytes >3,000/L; absolute neutrophil count >1,500/L; platelets >100,000/L; total bilirubin <1.5 X institutional upper limit of normal; AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal; Creatinine clearance > 50 ml/min At least 18 years of age, of either sex. If female, must be either (i) post-menopausal or surgically sterilized, or (ii) use a hormonal contraceptive, intra-uterine device, diaphragm with spermicide for the duration of the study and must be neither pregnant nor breast-feeding. Exclusion Criteria: Hypercalcaemia: calcium >= 2.7 mmol/L (10.8 mg/dL). Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin). More that 12 weeks after completion of primary radiotherapy. Had received prior adjuvant chemotherapy. Other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator). Have serious active infection. Patients with peripheral or ototoxicity with a grade of greater than 2. Pregnant or lactating female subjects and subjects with reproductive potential not implementing adequate contraceptive measures.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Adjuvant chemotherapy and then clinical follow-up and surveillance | Drug: Adjuvant chemotherapy (gemcitabine and cisplatin)<br>* Gemcitabine 1000 mg/m2 in 250 ml NS over 30 mins IV on Day 1 and 8 Cisplatin 40 mg/m2 in 1L NS over 2 h IV on Day 1 and 8 Cycle repeated every 3 weeks for total of 6 cycles<br>|
| No Intervention: B<br>Clinical follow-up and surveillance only | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse free survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is defined as the duration from the date of randomization to the date of death due to all causes or censored at the date of last follow-up | 5 years | 
| Loco-regional control |  | 5 years | 
| Metastasis-free survival |  | 5 years | 
| Toxicity of adjuvant chemotherapy |  | 6 months | 
| Correlation of plasma EBV DNA and PET/CT scan with clinical course and outcome |  | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nasopharyngeal cancer, adjuvant chemotherapy, EBV DNA, PET CT scan