Active, not recruiting
Phase 2/3
Individualized Treatment in Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA
Condition(s) studied
EBV InfectionStage II Nasopharyngeal Carcinoma AJCC v7Stage III Nasopharyngeal Carcinoma AJCC v7Stage IVA Nasopharyngeal Carcinoma AJCC v7Stage IVB Nasopharyngeal Carcinoma AJCC v7
Investigational drug(s) / intervention(s)
Bone ScanCisplatinClinical ObservationComputed TomographyFluorouracilGemcitabine HydrochlorideIntensity-Modulated Radiation TherapyLaboratory Biomarker AnalysisMagnetic Resonance ImagingPaclitaxelPositron Emission TomographyQuality-of-Life Assessment
Bone Scan: Undergo bone scan
Cisplatin: Given IV
Clinical Observation: Undergo clinical observation
Computed Tomography: Undergo CT scan
Fluorouracil: Given IV
Gemcitabine Hydrochloride: Given IV
Intensity-Modulated Radiation Therapy: Undergo IMRT
Laboratory Biomarker Analysis: Correlative studies
Magnetic Resonance Imaging: Undergo MRI
Paclitaxel: Given IV
Positron Emission Tomography: Undergo PET scan
Quality-of-Life Assessment: Ancillary studies
Study summary
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 and shrink tumors. 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.
Eligibility
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
* For patients who have detectable plasma EBV DNA tested at one of the credentialed central labs 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
* Stage II-IVB disease (American Joint Committee on Cancer \[AJCC\], 7th edition \[ed.\]) 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 Ear, Nose, Throat specialist (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:
* Magnetic resonance imaging (MRI) of the nasopharynx and neck; or computed tomography (CT) of the nasopharynx and neck with =\< 3 mm contiguous slices with contrast and bone windows (to evaluate base of skull involvement).
* 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)
* Zubrod performance status 0-1 within 21 days prior to registration
* Age \>= 18
* Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (within 21 days prior to registration)
* Platelets \>= 100,000 cells/mm\^3 (within 21 days prior to registration)
* Hemoglobin \>= 8.0 g/dl (within 21 days prior to registration) (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) (within 21 days prior to registration)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 1.5 x institutional ULN (within 21 days prior to registration)
* Alkaline phosphatase =\< 1.5 x institutional ULN (within 21 days prior to registration)
* 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 (within 21 days prior to registration)
* 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 that is tumor-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 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 past 6 months
* 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 registration
* 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
* 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
Primary outcome measure(s)
- Progression-free survival (PFS) (Detectable Plasma Epstein Barr virus [EBV] deoxyribonucleic acid [DNA] Cohort Phase II) — Up to 7 years
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided stratified log rank test. for stratification factors and concurrent cisplatin dose. A one-sided log rank test will be used to compare the PFS at a significance level of 0.1379.
- Overall survival (OS) (Undetectable Plasma EBV DNA Cohort Phase III) — Up to 7 years
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided stratified log rank test. for stratification factors and concurrent cisplatin dose. The confidence interval approach will be used for the final analysis of OS.
Trial sites (213)
| Facility | City | Region | Status |
| University of Alabama at Birmingham Cancer Center |
Birmingham |
Alabama |
|
| The Kirklin Clinic at Acton Road |
Birmingham |
Alabama |
|
| Banner University Medical Center - Tucson |
Tucson |
Arizona |
|
| Sutter Cancer Centers Radiation Oncology Services-Auburn |
Auburn |
California |
|
| Alta Bates Summit Medical Center-Herrick Campus |
Berkeley |
California |
|
| Mills-Peninsula Medical Center |
Burlingame |
California |
|
| Sutter Cancer Centers Radiation Oncology Services-Cameron Park |
Cameron Park |
California |
|
| City of Hope Comprehensive Cancer Center |
Duarte |
California |
|
| Kaiser Permanente Dublin |
Dublin |
California |
|
| Fresno Cancer Center |
Fresno |
California |
|
| UC San Diego Moores Cancer Center |
La Jolla |
California |
|
| Memorial Medical Center |
Modesto |
California |
|
| Kaiser Permanente Oakland-Broadway |
Oakland |
California |
|
| UC Irvine Health/Chao Family Comprehensive Cancer Center |
Orange |
California |
|
| Palo Alto Medical Foundation Health Care |
Palo Alto |
California |
|
| Stanford Cancer Institute Palo Alto |
Palo Alto |
California |
|
| Kaiser Permanente-Rancho Cordova Cancer Center |
Rancho Cordova |
California |
|
| Rohnert Park Cancer Center |
Rohnert Park |
California |
|
| Sutter Cancer Centers Radiation Oncology Services-Roseville |
Roseville |
California |
|
| The Permanente Medical Group-Roseville Radiation Oncology |
Roseville |
California |
|
| Sutter Medical Center Sacramento |
Sacramento |
California |
|
| University of California Davis Comprehensive Cancer Center |
Sacramento |
California |
|
| South Sacramento Cancer Center |
Sacramento |
California |
|
| California Pacific Medical Center-Pacific Campus |
San Francisco |
California |
|
| UCSF Medical Center-Mount Zion |
San Francisco |
California |
|
| UCSF Medical Center-Mission Bay |
San Francisco |
California |
|
| Kaiser Permanente Medical Center - Santa Clara |
Santa Clara |
California |
|
| City of Hope South Pasadena |
South Pasadena |
California |
|
| Kaiser Permanente Cancer Treatment Center |
South San Francisco |
California |
|
| Palo Alto Medical Foundation-Sunnyvale |
Sunnyvale |
California |
|
| Lutheran Hospital - Cancer Centers of Colorado |
Golden |
Colorado |
|
| Banner North Colorado Medical Center |
Greeley |
Colorado |
|
| Banner North Colorado Medical Center - Loveland Campus |
Loveland |
Colorado |
|
| AdventHealth Parker |
Parker |
Colorado |
|
| Intermountain Health Lutheran Hospital |
Wheat Ridge |
Colorado |
|
| Yale University |
New Haven |
Connecticut |
|
| Helen F Graham Cancer Center |
Newark |
Delaware |
|
| Christiana Care Health System-Christiana Hospital |
Newark |
Delaware |
|
| Baptist MD Anderson Cancer Center |
Jacksonville |
Florida |
|
| Moffitt Cancer Center |
Tampa |
Florida |
|
+ 173 more sites — see the full list on the official registry below.
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