Individualized Treatment in Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA

Inclusion Criteria:

• Biopsy proven (from primary lesion and/or lymph nodes) diagnosis of cancer of thenasopharynx

• Sites are required to complete Step 1 registration before submitting specimens forEBV DNA analysis.

• Patients must have detectable pretreatment plasma EBV DNA, determined by thecentral lab prior to Step 2 registration (see Section 10.2 for details ofspecimen submission).

• For patients who have detectable plasma EBV DNA tested at one of thecredentialed central labs (listed on the EBV DNA Testing Specimen Transmittalform) within 28 days prior to Step 1 registration: that test result can be usedfor eligibility without the need for re-testing. To use this test result foreligibility, the central lab must enter the test result through the pathologyportal, and the site must follow the instructions in Section 5.4.

• Stage II-IVB disease (AJCC, 7th ed.) with no evidence of distant metastasis, basedupon the following minimum diagnostic workup:

• History/physical examination by a Medical Oncologist or Clinical Oncologist orRadiation Oncologist or ENT, which must include an endoscopic evaluation, acomplete list of current medications, and assessment of weight and weight lossin the past 6 months within 21 days prior to registration;

• Evaluation of tumor extent required within 28 days prior to registration:

• MRI of the nasopharynx and neck; or CT of the nasopharynx and neck with ≤ 3 mmcontiguous slices with contrast and bone windows (to evaluate base of skullinvolvement).

Note: If a treatment planning CT scan is used, it must be with ≤ 3 mm contiguous slices with contrast and be read by a radiologist.

Please refer to section 6.3.2 for MRI requirement for target delineation.

• To rule out distant metastasis, patients must undergo the following imaging within 28 days prior to registration:

1. a CT scan with contrast of the chest and abdomen (required), and the pelvis (optional), or a total body PET/CT scan (non-contrast PET/CT is acceptable);

2. a bone scan only when there is suspicion of bone metastases (a PET/CT scan cansubstitute for the bone scan).

• Zubrod performance status 0-1 within 21 days prior to registration

• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3

• Platelets ≥ 100,000 cells/mm^3

• Hemoglobin ≥ 8.0 g/dl (Note: the use of transfusion or other intervention to achievehemoglobin [Hgb] ≥ 8.0 g/dl is acceptable)

• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 xinstitutional ULN

• Alkaline phosphatase ≤ 1.5 x institutional ULN

• Serum creatinine ≤ 1.5 mg/dl or calculated creatinine clearance (CC) ≥ 50 ml/mindetermined by 24-hour urine collection or estimated by Cockcroft-Gault formula

• Negative serum pregnancy test within 14 days prior to registration for women ofchildbearing potential

• Women of childbearing potential and male participants who are sexually active mustagree to use a medically effective means of birth control throughout protocoltreatment

• Patient must provide study specific informed consent prior to study entry, includingthe mandatory pre-treatment plasma EBV DNA assay

Exclusion Criteria:

• Prior invasive malignancy (except node negative, non-melanomatous skin cancer)unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma insitu of the breast, oral cavity, or cervix are all permissible)

• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for adifferent cancer is allowable; however, at least 6-weeks recovery is necessary ifthe last regimen included nitrosourea or mitomycin

• Prior radiotherapy to the region of the study cancer that would result in overlap ofradiation therapy fields

• Patients with hearing loss assessed to be primarily sensorineural in nature,requiring a hearing aid, or intervention (i.e. interfering in a clinicallysignificant way with activities of daily living); a conductive hearing loss that istumor-related is allowed

• ≥ Grade 2 peripheral sensory neuropathy (CTCAE, v. 4.0)

• Severe, active co-morbidity, defined as follows:

• Major medical or psychiatric illness, which in the investigator's opinion wouldinterfere with the completion of therapy and follow up or with fullunderstanding of the risks and potential complications of the therapy

• Unstable angina and/or uncontrolled congestive heart failure within the past 6months

• Myocardial infarction within the last 6 months

• Acute bacterial or fungal infection requiring intravenous antibiotics at thetime of registration; note that patients switched from IV antibiotics andcurrently on oral antibiotics whose infection is assessed to be adequatelytreated or controlled are eligible

• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illnessrequiring hospitalization or precluding study therapy within 30 days prior toregistration

• Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers forDisease Control and Prevention (CDC) definition; note, however, that HumanImmunodeficiency Virus (HIV) testing is not required for entry into thisprotocol. The need to exclude patients with AIDS from this protocol isnecessary because the treatments involved in this protocol may be significantlyimmunosuppressive.

• Pregnancy or women of childbearing potential and men who are sexually active and notwilling/able to use medically acceptable forms of contraception

• Prior allergic reaction to the study drug(s) involved in this protocol

• Patients with undetectable pre-treatment plasma EBV DNA