Clinical Trial ID: NCT02135042
Randomized Phase II and Phase III Studies of Individualized Treatment for Nasopharyngeal Carcinoma Based on Biomarker Epstein Barr Virus (EBV) Deoxyribonucleic Acid (DNA)
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.
The primary objective for randomized phase II is to determine whether substituting adjuvant CDDP and 5-FU with gemcitabine and paclitaxel will result in superior progression-free survival. The primary objective for phase III is to determine whether omitting adjuvant CDDP and 5-FU (observation alone in the adjuvant setting) will result in noninferior overall survival as compared with those patients receiving adjuvant CDDP and 5-FU chemotherapy.
Active Comparator: Chemo Radiation + Cisplatin + Fluorouracil 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. Experimental: Chemo Radiation + Gemcitabine Hydrochloride + Paclitaxel 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. Active Comparator: Chemo Radiation + Cisplatin + Fluorouracil Patients receive PF regimen as in Arm I of Phase II. Experimental: Chemo Radiation + Observation Patients undergo clinical observation.
Baptist MD Anderson Cancer Center
Inclusion Criteria: - Biopsy proven (from primary lesion and/or lymph nodes) diagnosis of cancer of the nasopharynx - Patients must have detectable pretreatment plasma EBV DNA, determined by the central lab prior to Step 2 registration - 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) or 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 treatment - 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 from tumor-related otitis media is allowed - >= Grade 2 peripheral sensory neuropathy (CTCAE, v. 4.0) - 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
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