Vaccine Therapy and Celecoxib in Treating Patients With Metastatic Nasopharyngeal Cancer

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a gene-modified virus and a person's dendritic cells may help the body build an effective immune response to kill tumor cells. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vaccine therapy together with celecoxib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving vaccine therapy together with celecoxib works in treating patients with metastatic nasopharyngeal cancer.

Detailed Description
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OBJECTIVES: Primary To evaluate the clinical benefit rate (complete response, partial response, and stable disease for ≥ 14 weeks) in patients with metastatic nasopharyngeal carcinoma treated with autologous dendritic cells (DC) transduced with AD5F35 expressing LMP-1 and LMP-2 when administered in combination with celecoxib. Secondary To evaluate the toxicities of this regimen in these patients. To evaluate the specific T-cell response against LMP-1 and LMP-2 as measured by HLA tetramer technology, ELISPOT assay, and delayed-type hypersensitivity in patients treated with this regimen. To evaluate the surrogate tumor marker response plasma EBV DNA by real-time PCR in these patients. To evaluate and characterize immunological cell types and tumor characteristics in biopsy specimens of patients treated with this DC vaccine and compare it with pre-vaccine biopsy specimens. To evaluate progression-free survival and overall survival of patients who show initial clinical benefit to DC vaccine. OUTLINE: Patients undergo blood collection for the preparation of the autologous dendritic cell (DC) vaccine. Immature DCs are transduced with latent membrane protein-1 (LMP-1) and latent membrane protein-2 (LMP-2) using the adenoviral vector 5F35. Beginning 1 week after blood collection, patients receive vaccination with autologous DCs transduced with AD5F35-LMP-1/LMP-2 intradermally every 2 weeks for a total of 5 vaccinations. Patients also receive celecoxib twice a day beginning 1 week before the first vaccination and continuing for up to 6 weeks after completion of the last vaccination. Patients who demonstrate clinical benefit after completion of 5 courses of vaccination may continue to receive the DC vaccine alone off study every 2 weeks until disease progression (based on CT scan findings) or at the investigator's discretion. Patients undergo blood and tumor tissue sample collection periodically for laboratory studies. Blood samples are analyzed using MHC tetramer analysis; enzyme-linked immunospot (ELISPOT) analysis; EBV DNA titers to assess response; and flow cytometry to assess lymphocyte kinetics. Tumor tissue samples are used for immunological studies. Delayed-type hypersensitivity is also assessed. After completion of study treatment, patients are followed monthly for up to 1 year.

Official Title
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Phase II Clinical Trial of Tumour Vaccination By Intradermal Delivery of Autologous Dendritic Cells Transduced With Adenoviral Vector (AD5F35) Expressing Latent Membrane Protein-1 (LMP-1) and Latent Membrane Protein-2 (LMP-2) Genes in Combination With Celecoxib in Patient With Metastatic Nasopharyngeal Carcinoma

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: Ad5F35-LMP1/LMP2-transduced autologous dendritic cells
* Drug: celecoxib
* Other: flow cytometry
* Other: immunoenzyme technique
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed nasopharyngeal carcinoma (NPC) Metastatic disease WHO type II/III disease Measurable disease Meets 1 of the following criteria: Progression on one or more lines of polychemotherapy for treatment of metastatic disease Failed non-myeloablative hematopoietic stem cell transplant No active CNS metastases PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy > 3 months Hemoglobin ≥ 8.5 g/dL Serum bilirubin ≤ 1.5 times upper limit of normal ALT or AST ≤ 5 times normal Creatinine clearance ≥ 40 mL/min Left ventricular ejection fraction ≥ 45% by MUGA Corrected DLCO > 50% of predicted No active or prior gastrointestinal bleeding No history of adverse reaction to NSAIDs or sensitivity to celecoxib No cardiac disease, including any of the following: Symptomatic congestive heart failure Active angina pectoris High-risk uncontrolled arrhythmia Uncontrolled hypertension No pulmonary disease, including any of the following: Severe chronic obstructive lung disease Uncontrolled large pleural effusion Severe restrictive lung disease No cerebrovascular accident No transient ischemic attack No HIV positivity No active uncontrolled infection No symptomatic leukoencephalopathy or other neuropsychiatric abnormalities Not pregnant or nursing Negative pregnancy test PRIOR CONCURRENT THERAPY: See Disease Characteristics Prior celecoxib allowed At least 28 days since prior chemotherapy At least 100 days since prior non-myeloablative hematopoietic stem cell transplant At least 2 months since prior donor lymphocyte infusions More than 28 days since prior participation in another clinical trial with any investigational drugs No other concurrent experimental drugs No other concurrent anticancer therapy No concurrent anticoagulation with warfarin or low molecular weight heparin No other concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Ad5F35-LMP1/LMP2-transduced autologous dendritic cells|nan|
|Drug: celecoxib|nan|
|Other: flow cytometry|nan|
|Other: immunoenzyme technique|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate (CBR) (complete response [CR], partial response [PR], and stable disease [SD] for ≥ 14 weeks) as defined by RECIST criteria |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (CR and PR) |  |  | 
| Overall survival |  |  | 
| Progression-free survival |  |  | 
| Toxicity profile |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV squamous cell carcinoma of the nasopharynx, stage IV lymphoepithelioma of the nasopharynx, recurrent squamous cell carcinoma of the nasopharynx, recurrent lymphoepithelioma of the nasopharynx