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

  • End date
    Jul 14, 2026
  • participants needed
  • sponsor
    NRG Oncology
Updated on 4 October 2022


There are two study questions we are asking in this randomized phase II/III trial based on a blood biomarker, Epstein Barr virus (EBV) deoxyribonucleic acid (DNA) for locoregionally advanced non-metastatic nasopharyngeal cancer. All patients will first undergo standard concurrent chemotherapy and radiation therapy. When this standard treatment is completed, if there is no detectable EBV DNA in their plasma, then patients are randomized to either standard adjuvant cisplatin and fluorouracil chemotherapy or observation. If there is still detectable levels of plasma EBV DNA, patients will be randomized to standard cisplatin and fluorouracil chemotherapy versus gemcitabine and paclitaxel. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, fluorouracil, gemcitabine hydrochloride, and paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cisplatin and fluorouracil is more effective than gemcitabine hydrochloride and paclitaxel after radiation therapy in treating patients with nasopharyngeal cancer.



I. To determine whether substituting adjuvant concurrent high dose cisplatin (CDDP) and fluorouracil (5-FU) with gemcitabine (gemcitabine hydrochloride) and paclitaxel will result in superior progression-free survival. (Detectable Plasma Epstein Barr Virus [EBV] Deoxyribonucleic Acid [DNA] Cohort randomized Phase II) II. To determine whether omitting adjuvant CDDP and 5-FU (observation alone in the adjuvant setting) will result in non-inferior overall survival as compared with those patients receiving adjuvant CDDP and 5-FU chemotherapy. (Undetectable Plasma EBV DNA Cohort Phase III)


I. Time to distant metastasis. (Randomized Phase II and Phase III) II. Time to local progression. (Randomized Phase II and Phase III) III. Time to regional progression. (Randomized Phase II and Phase III) IV. Progression-free survival (Undetectable Cohort). V. Overall survival (Detectable Cohort). VI. Acute and late toxicity profiles based on clinician-reported Common Terminology Criteria for Adverse Events (CTCAE), version (v.) 4. (Randomized Phase II and Phase III) VII. Death during or within 30 days of end of protocol treatment. (Randomized Phase II and Phase III) VIII. Quality of life (general and physical well-being). (Randomized Phase II and Phase III) IX. Quality of life (hearing). (Randomized Phase II and Phase III) X. Quality of life (peripheral neuropathy). (Randomized Phase II and Phase III) XI. Cost effectiveness. (Randomized Phase II and Phase III)


Patients undergo intensity modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6.5 weeks and receive low-dose cisplatin intravenously (IV) over 30-60 minutes once weekly during IMRT. Beginning 1 week after chemoradiation, plasma samples are collected for EBV DNA analysis.

PHASE II: Patients with detectable EBV DNA from pre-treatment analysis are randomized to 1 of 2 treatment arms.

ARM I: Patients receive PF regimen comprising cisplatin IV over 60-120 minutes and fluorouracil IV over 96 hours continuously beginning at least 4 weeks after completion of IMRT. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.


Patients with undetectable EBV DNA from pre-treatment analysis are randomized to 1 of 2 treatment arms.

ARM III: Patients receive PF regimen as in Arm I.

ARM IV: Patients undergo clinical observation.

After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Condition Epstein-Barr Virus Infection, Stage II Nasopharyngeal Carcinoma, Stage III Nasopharyngeal Carcinoma, Stage IVA Nasopharyngeal Carcinoma, Stage IVB Nasopharyngeal Carcinoma
Treatment clinical observation, fluorouracil, laboratory biomarker analysis, cisplatin, gemcitabine hydrochloride, quality-of-life assessment, Paclitaxel, intensity-modulated radiation therapy
Clinical Study IdentifierNCT02135042
SponsorNRG Oncology
Last Modified on4 October 2022


Yes No Not Sure

Inclusion Criteria

Biopsy proven (from primary lesion and/or lymph nodes) diagnosis of cancer of the nasopharynx
Sites are required to complete Step 1 registration before submitting specimens for EBV DNA analysis
Patients must have detectable pretreatment plasma EBV DNA, determined by the central lab prior to Step 2 registration (see Section 10.2 for details of specimen submission)
For patients who have detectable plasma EBV DNA tested at one of the credentialed central labs (listed on the EBV DNA Testing Specimen Transmittal form) within 28 days prior to Step 1 registration: that test result can be used for eligibility without the need for re-testing. To use this test result for eligibility, the central lab must enter the test result through the pathology portal, and the site must follow the instructions in Section 5.4
Stage II-IVB disease (AJCC, 7th ed.) with no evidence of distant metastasis, based
History/physical examination by a Medical Oncologist or Clinical Oncologist or Radiation Oncologist or ENT, which must include an endoscopic evaluation, a complete list of current medications, and assessment of weight and weight loss in the past 6 months within 21 days prior to registration
upon the following minimum diagnostic workup
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 mm
Zubrod performance status 0-1 within 21 days prior to registration
contiguous slices with contrast and bone windows (to evaluate base of skull
Please refer to section 6.3.2 for MRI requirement for target delineation
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
To rule out distant metastasis, patients must undergo the following imaging within 28
days prior to registration
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)
a bone scan only when there is suspicion of bone metastases (a PET/CT scan can
substitute for the bone scan)
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 achieve
hemoglobin [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 x
institutional ULN
Alkaline phosphatase ≤ 1.5 x institutional ULN
Serum creatinine ≤ 1.5 mg/dl or calculated creatinine clearance (CC) ≥ 50 ml/min
determined by 24-hour urine collection or estimated by Cockcroft-Gault formula
Negative serum pregnancy test within 14 days prior to registration for women of
childbearing potential
Women of childbearing potential and male participants who are sexually active must
agree to use a medically effective means of birth control throughout protocol
Patient must provide study specific informed consent prior to study entry, including
the mandatory pre-treatment plasma EBV DNA assay

Exclusion Criteria

Severe, active co-morbidity, defined as follows
Myocardial infarction within the last 6 months
Prior allergic reaction to the study drug(s) involved in this protocol
Patients with undetectable pre-treatment plasma EBV DNA
Prior invasive malignancy (except node negative, non-melanomatous skin cancer) unless
disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of
the breast, oral cavity, or cervix are all permissible)
Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable; however, at least 6-weeks recovery is necessary if the
last regimen included nitrosourea or mitomycin
Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields
Patients with hearing loss assessed to be primarily sensorineural in nature, requiring
a hearing aid, or intervention (i.e. interfering in a clinically significant way with
activities of daily living); a conductive hearing loss that is tumor-related is
≥ Grade 2 peripheral sensory neuropathy (CTCAE, v. 4.0)
Major medical or psychiatric illness, which in the investigator's opinion would
interfere with the completion of therapy and follow up or with full understanding
of the risks and potential complications of the therapy
Unstable angina and/or uncontrolled congestive heart failure within the past 6
Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration; note that patients switched from IV antibiotics and currently on
oral antibiotics whose infection is assessed to be adequately treated or
controlled are eligible
Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days prior to
Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease
Control and Prevention (CDC) definition; note, however, that Human
Immunodeficiency Virus (HIV) testing is not required for entry into this
protocol. The need to exclude patients with AIDS from this protocol is necessary
because the treatments involved in this protocol may be significantly
Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note