Phase II Trial Evaluating Efficacy of a Strategy Employing Combination Gemcitabine and Carboplatin Chemotherapy Followed by EBV-Specific Cytotoxic T-Lymphocytes in Patients With Metastatic or Locally Recurrent EBV-Positive Nasopharyngeal Carcinoma
21 Years
N/A
Both
Head and Neck Cancer
Trial Information
Phase II Trial Evaluating Efficacy of a Strategy Employing Combination Gemcitabine and Carboplatin Chemotherapy Followed by EBV-Specific Cytotoxic T-Lymphocytes in Patients With Metastatic or Locally Recurrent EBV-Positive Nasopharyngeal Carcinoma
OBJECTIVES:
Primary
- To determine progression-free survival (PFS 1) of patients with metastatic or locally
recurrent Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma treated with
gemcitabine hydrochloride and carboplatin followed EBV-specific cytotoxic T-lymphocytes
(CTL).
Secondary
- To determine progression-free survival (PFS 2) of these patients during the
immunotherapy portion of this study.
- To determine the clinical benefit rate of EBV-specific CTL in these patients.
- To determine the tolerability of EBV-specific CTL therapy in these patients.
- To demonstrate persistence of EBV-specific immune response in these patients.
OUTLINE: Patients undergo collection of peripheral blood mononuclear cells (PBMC) from which
T cells are purified, co-cultured with irradiated autologous Epstein-Barr virus
(EBV)-specific cytotoxic T-lymphocytes (CTLs), and expanded in vitro for the establishment
of cytotoxic T-cell lines.
- Chemotherapy: Patients receive gemcitabine hydrochloride IV over 30 minutes and
carboplatin IV over 60 minutes on days 1, 8, and 15. Treatment repeats every 28 days
for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of course 2, patients undergo evaluation for response. Patients with
progressive disease proceed directly to induction immunotherapy. Patients with stable
disease (SD), partial response (PR), or complete response (CR) receive 2 additional
courses of chemotherapy and then proceed to induction immunotherapy.
- Induction immunotherapy: Beginning 14-28 days after the completion of chemotherapy,
patients receive EBV-specific CTLs IV over 1-10 minutes on days 1 and 14. Six weeks
after the second infusion, patients undergo evaluation for response. Patients who
demonstrate clinical benefit (i.e., CR, PR, SD) to induction immunotherapy proceed to
maintenance immunotherapy.
- Maintenance immunotherapy: Patients receive EBV-specific CTLs IV over 1-10 minutes.
Treatment repeats every 1-3 months for up to 4 courses in the absence of disease
progression or unacceptable toxicity.
Patients undergo blood sample collection at baseline and prior to each course of induction
immunotherapy and maintenance immunotherapy. Samples are analyzed for EBV CTL frequency by
immune function assays (i.e., tetramer analysis, enzyme-linked immunospot, and cytotoxic
T-lymphocyte precursor assays); for specificity of response by cytotoxicity assays (in
patients for whom the appropriate reagents are available); and for evaluation of EBV DNA by
polymerase chain reaction. In addition, T-cells are isolated from blood samples for
fluorescence-activated cell sorter analysis and for extraction of RNA.
After completion of study therapy, patients are followed at least every 2 months until
disease progression.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Biopsy-proven nasopharyngeal carcinoma (NPC)
- WHO type 2/3 disease
- Metastatic or locally recurrent disease
- Epstein-Barr virus (EBV)-positive disease as confirmed by in situ hybridization assay
or PCR amplification for EBV-encoded RNA expression
- Radiologically measurable disease
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 3 months
- ANC > 1,200/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 8 g/dL
- Bilirubin < 2 times upper limit of normal (ULN)
- AST and ALT < 3 times ULN
- Creatinine clearance ≥ 40 mL/min
- Corrected calcium normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No concurrent severe illness, including any of the following:
- Chronic obstructive pulmonary disease
- Ischemic heart disease
- Active congestive cardiac failure
- Active angina pectoris
- Uncontrolled arrhythmia
- Uncontrolled hypertension
- No concurrent severe infections
- HIV negative
PRIOR CONCURRENT THERAPY:
- No more than one line of prior chemotherapy for metastatic disease
- No prior gemcitabine hydrochloride
- Prior platinum agents allowed
- At least 1 month since prior investigational therapy
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Median progression-free survival (PFS 1), defined as the time from study enrollment to the time of radiological disease progression or death from any cause
Safety Issue:
No
Principal Investigator
Toh Han Chong, MD, MBBS, MRCP
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Cancer Centre, Singapore
Authority:
Unspecified
Study ID:
CDR0000577971
NCT ID:
NCT00690872
Start Date:
July 2008
Completion Date:
Related Keywords:
- Head and Neck Cancer
- recurrent lymphoepithelioma of the nasopharynx
- recurrent squamous cell carcinoma of the nasopharynx
- stage IV lymphoepithelioma of the nasopharynx
- stage IV squamous cell carcinoma of the nasopharynx
- Head and Neck Neoplasms
- Nasopharyngeal Neoplasms
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