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

Not Recruiting

Trial ID: NCT02135042,18,48550


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.

Official Title

Randomized Phase II and Phase III Studies of Individualized Treatment for Nasopharyngeal Carcinoma Based on Biomarker Epstein Barr Virus (EBV) Deoxyribonucleic Acid (DNA)

Stanford Investigator(s)

Quynh-Thu Le, MD
Quynh-Thu Le, MD

Katharine Dexter McCormick and Stanley McCormick Memorial Professor and Professor, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS)

A. Dimitrios Colevas, MD
A. Dimitrios Colevas, MD

Professor of Medicine (Oncology) and, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS) and of Radiation Oncology (Radiation Therapy)


Inclusion Criteria:

   - Biopsy proven (from primary lesion and/or lymph nodes) diagnosis of cancer of the

   - 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
   upon the following minimum diagnostic workup:

      - 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;

      - 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
   contiguous slices with contrast and bone windows (to evaluate base of skull

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 can
      substitute 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 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:

   - 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)

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

      - 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

      - Myocardial infarction within the last 6 months

      - 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

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

   - Patients with undetectable pre-treatment plasma EBV DNA


drug: cisplatin

radiation: intensity-modulated radiation therapy

drug: fluorouracil

drug: gemcitabine hydrochloride

drug: paclitaxel

other: clinical observation

other: quality-of-life assessment

other: laboratory biomarker analysis

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Samantha Wong

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