Phase I/II Trial of Latent Membrane Protein (LMP) - 2 Immunization for the Assessment of the Natural History and the Immunization-Induced Immunological Response in Patients at High Risk for Recurrence of Anaplastic Nasopharyngeal Cancer
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.