advanced Nasopharyngeal Carcinoma, uitbehandeld Nasopharynx Carcinoom. metastatic Nasopharyngeal Carcinoma, gemetastaseerd Nasopharynx Carcinoom.
Conditions
Interventions
Patients will receive VPA given orally on day 1 (12.5 mg/kg/day) during 14 days. GCb (1250 mg/m2) will be given at day 1 and 8 intravenously. At day 9 GCV will be given orally daily till day 22 (3x 45
Sponsors
sponsor:ZonMW
perfomers: the Netherlands Cancer Institute/ Antoni van Leeuwenhoek Hospital
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patient has histological confirmed residual, recurrent or metastatic nasopharyngeal carcinoma that has failed conventional curative treatments and deemed incurable, or patient refuses further treatment with conventional methods because of associated morbidity/mortality or private reasons; 2. Confirmed EBV positive NPC; 3. Measurable disease, according to RECIST criteria; 4. WHO PS 0-2; 5. Minimal acceptable safety laboratory values: A. ANC of ≥ 1.5 × 109/L; B. Platelet count of ≥ 100 × 109/L; C. Haemoglobin level of ≥ 10 g/dL (≥ 6.2 mmol/L) (prior transfusion is permitted); D. Hepatic function as defined by serum bilirubin ≤ 1.25 times the upper limit of normal (ULN), ALT and AST ≤ 2.5 times the ULN; E. Renal function as defined by serum creatinine ≤ 1.25 times ULN or creatinine clearance ≥ 50 m/min (by Cockcroft-Gault formula). 6. Age 18-70 years; 7. Signed written informed consent before any study related activities are carried out; 8. Expected adequacy of follow-up.
Exclusion criteria
Exclusion criteria: 1. Active infection (infection requiring IV antibiotics), including active tuberculosis, and known and declared HIV; 2. Pregnancy (absence confirmed by serum or urine β-HCG test) or lactation period; 3. Concurrent treatment with any other anti-cancer therapy; 4. Class 3-4 cardiac morbidity, as defined by the New York Heart association Criteria (e.g. uncontrolled or symptomatic congestive heart failure, myocardial infarction within six months prior to the start of study, uncontrolled or symptomatic angina) and any cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient; 5. Current active hepatic or biliary disease (with exception of Gilbert’s syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment); 6. Presence of severe and/or uncontrolled concurrent medical disease (e.g. uncontrolled diabetes mellitus, uncontrolled liver disease, including chronic viral hepatitis judged at risk of reactivation, uncontrolled active infection such as HIV infection, etc.); 7. Concomitant (or within 4 weeks before randomization) administration of any other experimental drug under investigation; chemotherapy or other anti-cancer therapy for the recurrence or metastatic disease; chemotherapy for initial treatment, i.e. chemoradiotherapy, is allowed; 8. Concurrent or previous malignancy of a different tumor type within five years of starting the study except for adequately treated non-melanoma skin cancer or cervical intraepithelial neoplasia; 9. Legal incapacity; 10. History of malabsorption syndrome or other disease that could significantly affect absorption of drugs; 11. Systemic steroids within 2 weeks prior to study treatment; 12. Myocardial infarction or cerebrovascular accident (CVA) within 6 months prior to study treatment; 13. Patients who have known hypersensitivity to the study medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability endopoints of combination treatment, i.e. GCb, VPA and GCV, will consist of the evaluation of adverse events (AE’s) serious adverse events (SAE’s) and all clinically significant changes in clinical laboratory values. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Analysis of pharmacokinetic and pharmacodynamic changes during lytic induction therapy. The pharmacokinetic and pharmacodynamic profile of GCb, VPA and GCV. Pharmacokinetic endpoints will consist of parameters such as AUC, Css, Cmax, tmax and t1/2 of i.v. Gemcitabine and oral VPA and GCV in combination; 2. Analysis of clinical response: Assessment (according to RECIST criteria) of anti-tumor activity will be obtained every 2 cycles (12 weeks) and will be recorded as complete response, partial response, stable disease or progressive disease; 3. Analysis of biological effect of the lytic induction therapy: In order to evaluate therapy induced changes in EBV antigen presentation specific EBV DNA and RNA profiling methods will be used to accurately monitor EBV-driven gene activation and transcription. In addition, levels and diversity in the humoral immune responses and EBV specific T-cell responses will be assessed during treatment in patients with suitable HLA types by in vitro incubation with EBV specific tetramers. | — |
Contacts
Public ContactM. Wildeman
NKI-AvL, Dept. H&N Oncology-Surgery Plesmanlaan 121
Outcome results
None listed