This study will examine the effectiveness and side effects of an experimental vaccine to
prevent recurrence of nasopharyngeal cancer. The likelihood of this cancer returning is
higher in patients whose original lesion was large, whose cancer had spread to the adjacent
lymph nodes, or who had surgery for metastatic disease (cancer that spread beyond the
primary site). Nasopharyngeal tumors are caused by a common virus called Epstein-Barr virus,
which produces a protein called LMP-2. Vaccination with specific pieces, or peptides, of the
LMP-2 protein may boost the immune system's fight against the cancer. The vaccine injections
are mixed with an oil-based substance called Montanide ISA-51, which is intended to increase
the immune response to the peptide.
Patients 18 years of age and older whose nasopharyngeal cancer has been controlled by
standard treatment with surgery, chemotherapy, or radiation therapy and who are currently
free of disease may be eligible for this study. Candidates are screened with a physical
examination and blood and urine tests. x-rays and other imaging studies are also done in
patients who have not had these tests recently. All candidates are tested for HLA tissue
type. Only patients with type HLA-A*1101 or HLA-A*2402 - the types on which the two vaccines
in this study are based - receive vaccine therapy; others are offered standard medical
treatment and observation.
Participants are randomly assigned to receive injections of one of two different vaccines
(LMP-2:340-349 or LMP-2:419-427) to determine which peptide may offer the best immunity.
Each treatment course consists of weekly immunizations for 8 consecutive weeks. The
injections are given under the skin of the thigh. After every other treatment course (about
every 3 months), patients undergo a series of x-rays and scans to look for tumor. The
immunizations are given at the NIH Clinical Center. Patients are monitored for 1 hour after
each injection and have blood tests and a physical examination to look for treatment side
effects. Immunizations may continue for up to 12 months as long as the cancer does not
Patients are followed with blood tests every 12 weeks to monitor body functions. They also
undergo leukapheresis-a procedure to collect white blood cells-before starting treatment and
about 3 to 4 weeks after the fourth vaccine to evaluate how the vaccines affect the action
of the immune system cells. For this procedure, blood is drawn through a needle in the arm,
similar to donating blood. The blood is processed by a machine that separates and removes
the lymphocytes (white blood cells), and the rest of the blood is returned through a needle
in the other arm. Patients not receiving the vaccine also undergo leukapheresis to assess
their natural response to LMP-2. Some patients may have a biopsy-surgical removal of a small
piece of tissue under local anesthetic-of normal skin and tumor or lymph node tissue to
examine the vaccine's effects on the tumor immune cells.
Patients who show no evidence of immunization against the LMP-2 protein after two courses of
vaccine treatment are subsequently be followed with observation alone. Those who do respond
to the vaccine are offered two additional courses of treatment to strengthen the response or
to be followed by observation alone. Patients whose disease recurs after completing the
first two treatment courses are taken off the study and referred back to their local
physician or to another study, if an appropriate one is available.
HLA-A*1101 and HLA-A*2402 positive patients with locally controlled anaplastic
nasopharyngeal carcinoma at risk for loco-regional or distant recurrence will receive
immunization with peptides representing HLA-restricted T cell epitopes of the Epstein-Barr
virus encoded latent membrane protein-2 (LMP-2) emulsified in Montanide ISA-51. Patients
will be allocated to treatment according to their HLA phenotype. The immunologic potential
of the vaccine will be followed by enumerating the frequency of vaccines-specific CD8+ T
cells in the peripheral blood using tetrameric HLA/peptide complexes. This study is designed
to evaluate the immunologic effectiveness of peptide immunization in adjuvant settings in
the context of anaplastic NPC.
1. HLA-A*1101 and HLA-A*2402 patients, greater than 18 years of age, with advanced local
disease (T3-T4N0-1M0), nodal disease (T1-T2N2-3M0) and loco-regional disease
(T3-T4N2-3M0) at onset but presently controlled by standard therapy (combination of
chemotherapy and radiotherapy) or with completely resected metastatic disease, 3
months after the completion of their primary treatment will be considered.
All subjects will be judged disease free based on physical examination, ENT
endoscopy, CT scan of abdomen, chest, neck and nasal sinuses and MRI of the head.
All subjects must have received standard surgical, chemotherapy and radiation therapy
appropriate for their stage of disease.
Currently, standard treatment for locally advanced NPC in the U.S. consists of
concomitant cisplatin with radiation followed by 3 courses of cisplatin and
5-fluorouracil. This, or comparable standard therapies will be considered part of
standard therapy and patients will be considered for accrual three or more months
after its completion. Patients must demonstrate evidence of local control with no
histological or radiological evidence of recurrent disease three months after the end
of standard therapy and be, otherwise, clinically disease free at the time of
protocol entry as documented by radiological studies within 6 weeks of patient entry.
Physical and histological evidence of disease recurrence at the time of patients'
screening and during follow up will be performed under the supervision of Dr. Carter
Van Waes during an out patient evaluation. Similar enrollment criteria will be used
with patients who do not bear HLA-A*1101 or HLA-A*2402. However, these patients will
be followed by observation only.
2. Pathologic confirmation of nasopharyngeal carcinoma by the NCI Laboratory of
3. serum creatinine of 2.0 mg/dl or less,
4. Total bilirubin 1.6 mg/dl or less, except for patients with Gilbert's Syndrome who
must have a total bilirubin less than 3.0 mg/dl.
5. WBC 3000/mm(3) or greater,
6. platelet count 90,000 mm(3) or greater,
7. serum AST/ALT less than three times normal,
8. ECOG performance status of 0 or 1.
9. Patients of both genders must be willing to practice effective birth control during
this trial because the potential for teratogenic effects are unknown.
10. Patients may have had prior adjuvant treatment or may have had treatment for
metastatic disease and are now with no evidence of disease, including chemotherapy or
biotherapy, as long as 1 month has elapsed since prior systemic therapy.
Patients will be excluded:
1. Who are undergoing or have undergone in the past 3 weeks any systemic therapy except
surgery for their cancer, and must have recovered from any adverse effects of
treatment prior to entry, other than those that do not have clinical implications,
e.g. alopecia. In the case a patient has received surgical intervention; at least
one month should pass before enrollment in the study. All toxicity from previous
therapy must have resolved to less than or equal to Grade 1 by NCI-CTC v 3.0 before
2. Who have active systemic infections, autoimmune disease or any known immunodeficiency
d. Who require systemic steroid therapy.
e. Who are pregnant (because of possible side effects on the fetus) or breastfeeding
(because of unknown effects on the developing child).
f. Who are known to be positive for hepatitis BsAG or HIV antibody (because of possible
immune effects of these conditions). Patients who may screen or have history positive for
hepatitis C may be enrolled if their transaminases levels are within the limits specified
in inclusion criteria.
g. Who have any form of active primary or secondary immunodeficiency or who have not
recovered immune competence after chemotherapy or radiation therapy. (The experimental
treatment being evaluated in this protocol depends on an intact immune system. Patients
who have decreased immune competence may be less responsive to the experimental treatment
and more susceptible to its toxicities.) Active or secondary immunodeficiency will be
judged based on the patient past medical history and normality of circulating T and B cell
counts (Normal range 650-2, 108 and 49 to 424 respectively, Department of Laboratory
Medicine, CC). In the similar fashion recovery from chemotherapy and radiation therapy
will be evaluated. Previous experience in patients with melanoma or renal cell carcinoma
who underwent chemotherapy of local radiation demonstrated that they immune response to
common T cell epitopes such as Flu or Cytomegalovirus are rapidly restored within the
first month from such treatment (unpublished observation).
h. Who have known hypersensitivity to any of the agents used in this study.