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

Primary Purpose

Epstein-Barr Virus Infection, Stage II Nasopharyngeal Carcinoma, Stage III Nasopharyngeal Carcinoma

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cisplatin
Clinical Observation
Fluorouracil
Gemcitabine Hydrochloride
Intensity-Modulated Radiation Therapy
Laboratory Biomarker Analysis
Paclitaxel
Quality-of-Life Assessment
Sponsored by
NRG Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epstein-Barr Virus Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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 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.

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 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 the 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. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
  • 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

Sites / Locations

  • University of Alabama at Birmingham Cancer Center
  • The Kirklin Clinic at Acton Road
  • Banner University Medical Center - Tucson
  • Sutter Cancer Centers Radiation Oncology Services-Auburn
  • Alta Bates Summit Medical Center-Herrick Campus
  • Mills-Peninsula Medical Center
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
  • City of Hope Comprehensive Cancer Center
  • Kaiser Permanente Dublin
  • Fresno Cancer Center
  • UC San Diego Moores Cancer Center
  • Memorial Medical Center
  • Kaiser Permanente Oakland-Broadway
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
  • Palo Alto Medical Foundation Health Care
  • Stanford Cancer Institute Palo Alto
  • Kaiser Permanente-Rancho Cordova Cancer Center
  • Rohnert Park Cancer Center
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
  • The Permanente Medical Group-Roseville Radiation Oncology
  • Sutter Medical Center Sacramento
  • University of California Davis Comprehensive Cancer Center
  • South Sacramento Cancer Center
  • California Pacific Medical Center-Pacific Campus
  • UCSF Medical Center-Mount Zion
  • UCSF Medical Center-Mission Bay
  • Kaiser Permanente Medical Center - Santa Clara
  • City of Hope South Pasadena
  • Kaiser Permanente Cancer Treatment Center
  • Palo Alto Medical Foundation-Sunnyvale
  • Sutter Cancer Centers Radiation Oncology Services-Vacaville
  • SCL Health Cancer Centers of Colorado - Lutheran Medical Center
  • North Colorado Medical Center
  • McKee Medical Center
  • Parker Adventist Hospital
  • SCL Health Lutheran Medical Center
  • Yale University
  • Helen F Graham Cancer Center
  • Christiana Care Health System-Christiana Hospital
  • Baptist MD Anderson Cancer Center
  • Moffitt Cancer Center
  • Emory Proton Therapy Center
  • Emory University Hospital Midtown
  • Emory University Hospital/Winship Cancer Institute
  • Emory Saint Joseph's Hospital
  • The Cancer Center of Hawaii-Pali Momi
  • Queen's Medical Center
  • The Cancer Center of Hawaii-Liliha
  • Saint Alphonsus Cancer Care Center-Boise
  • Rush - Copley Medical Center
  • Northwestern University
  • John H Stroger Jr Hospital of Cook County
  • Cancer Care Specialists of Illinois - Decatur
  • Decatur Memorial Hospital
  • Crossroads Cancer Center
  • Memorial Medical Center
  • Carle Cancer Center
  • Memorial Hospital of South Bend
  • Iowa Methodist Medical Center
  • University of Iowa/Holden Comprehensive Cancer Center
  • Ascension Via Christi Hospitals Wichita
  • Wesley Medical Center
  • Greater Baltimore Medical Center
  • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Tufts Medical Center
  • Massachusetts General Hospital Cancer Center
  • Boston Medical Center
  • Saint Joseph Mercy Hospital
  • University of Michigan Comprehensive Cancer Center
  • McLaren Cancer Institute-Bay City
  • Henry Ford Cancer Institute-Downriver
  • Saint Joseph Mercy Canton
  • McLaren Cancer Institute-Clarkston
  • Henry Ford Macomb Hospital-Clinton Township
  • Wayne State University/Karmanos Cancer Institute
  • Henry Ford Hospital
  • Weisberg Cancer Treatment Center
  • McLaren Cancer Institute-Flint
  • Singh and Arora Hematology Oncology PC
  • Karmanos Cancer Institute at McLaren Greater Lansing
  • Mid-Michigan Physicians-Lansing
  • Sparrow Hospital
  • McLaren Cancer Institute-Lapeer Region
  • Trinity Health Saint Mary Mercy Livonia Hospital
  • McLaren Cancer Institute-Macomb
  • McLaren Cancer Institute-Central Michigan
  • McLaren Cancer Institute-Northern Michigan
  • Saint Joseph Mercy Oakland
  • McLaren-Port Huron
  • Ascension Saint Mary's Hospital
  • Henry Ford West Bloomfield Hospital
  • Fairview Ridges Hospital
  • Minnesota Oncology - Burnsville
  • Unity Hospital
  • Minnesota Oncology Hematology PA-Maplewood
  • Abbott-Northwestern Hospital
  • Hennepin County Medical Center
  • North Memorial Medical Health Center
  • Mayo Clinic in Rochester
  • Regions Hospital
  • Rice Memorial Hospital
  • Saint Francis Medical Center
  • Siteman Cancer Center at West County Hospital
  • Delbert Day Cancer Institute at PCRMC
  • Washington University School of Medicine
  • Siteman Cancer Center-South County
  • Mercy Hospital Saint Louis
  • Siteman Cancer Center at Saint Peters Hospital
  • Mercy Hospital Springfield
  • CoxHealth South Hospital
  • Saint James Community Hospital and Cancer Treatment Center
  • Nebraska Methodist Hospital
  • Radiation Oncology Centers of Nevada Central
  • Radiation Oncology Centers of Nevada Southeast
  • Renown Regional Medical Center
  • Saint Mary's Regional Medical Center
  • Memorial Sloan Kettering Basking Ridge
  • Memorial Sloan Kettering Monmouth
  • Memorial Sloan Kettering Bergen
  • Rutgers Cancer Institute of New Jersey
  • Rutgers New Jersey Medical School
  • Montefiore Medical Center-Einstein Campus
  • Montefiore Medical Center - Moses Campus
  • New York-Presbyterian/Brooklyn Methodist Hospital
  • Maimonides Medical Center
  • Memorial Sloan Kettering Commack
  • Memorial Sloan Kettering Westchester
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone
  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
  • New York Proton Center
  • Memorial Sloan Kettering Cancer Center
  • University of Rochester
  • Memorial Sloan Kettering Sleepy Hollow
  • Memorial Sloan Kettering Nassau
  • Cleveland Clinic Akron General
  • Geauga Hospital
  • University of Cincinnati Cancer Center-UC Medical Center
  • Case Western Reserve University
  • Cleveland Clinic Cancer Center/Fairview Hospital
  • Cleveland Clinic Foundation
  • Ohio State University Comprehensive Cancer Center
  • Mercy Cancer Center-Elyria
  • Cleveland Clinic Cancer Center Mansfield
  • North Coast Cancer Care
  • Cleveland Clinic Cancer Center Strongsville
  • ProMedica Flower Hospital
  • University of Cincinnati Cancer Center-West Chester
  • UHHS-Westlake Medical Center
  • Cleveland Clinic Wooster Family Health and Surgery Center
  • University of Oklahoma Health Sciences Center
  • Mercy Hospital Oklahoma City
  • Legacy Mount Hood Medical Center
  • Legacy Good Samaritan Hospital and Medical Center
  • Christiana Care Health System-Concord Health Center
  • Geisinger Medical Center
  • Geisinger Medical Oncology-Lewisburg
  • Lewistown Hospital
  • Geisinger Cancer Services-Pottsville
  • Reading Hospital
  • Geisinger Wyoming Valley/Henry Cancer Center
  • Prisma Health Cancer Institute - Spartanburg
  • Prisma Health Cancer Institute - Faris
  • Saint Francis Cancer Center
  • Prisma Health Cancer Institute - Eastside
  • Prisma Health Cancer Institute - Greer
  • Gibbs Cancer Center-Pelham
  • Prisma Health Cancer Institute - Seneca
  • Spartanburg Medical Center
  • UT Southwestern/Simmons Cancer Center-Dallas
  • M D Anderson Cancer Center
  • American Fork Hospital / Huntsman Intermountain Cancer Center
  • Sandra L Maxwell Cancer Center
  • Logan Regional Hospital
  • Intermountain Medical Center
  • McKay-Dee Hospital Center
  • Utah Valley Regional Medical Center
  • Riverton Hospital
  • Saint George Regional Medical Center
  • Utah Cancer Specialists-Salt Lake City
  • Inova Schar Cancer Institute
  • Inova Fairfax Hospital
  • Naval Medical Center - Portsmouth
  • Legacy Salmon Creek Hospital
  • Langlade Hospital and Cancer Center
  • HSHS Sacred Heart Hospital
  • Marshfield Medical Center-EC Cancer Center
  • Gundersen Lutheran Medical Center
  • University of Wisconsin Carbone Cancer Center
  • Marshfield Medical Center-Marshfield
  • Marshfield Medical Center
  • Medical College of Wisconsin
  • Marshfield Clinic-Minocqua Center
  • Marshfield Medical Center-Rice Lake
  • Ascension Saint Michael's Hospital
  • Marshfield Medical Center-River Region at Stevens Point
  • Aspirus Regional Cancer Center
  • Diagnostic and Treatment Center
  • Marshfield Medical Center - Weston
  • Aspirus Cancer Care - Wisconsin Rapids
  • Peter MacCallum Cancer Centre
  • Tom Baker Cancer Centre
  • Cross Cancer Institute
  • London Regional Cancer Program
  • University Health Network-Princess Margaret Hospital
  • McGill University Department of Oncology
  • The Research Institute of the McGill University Health Centre (MUHC)
  • Jewish General Hospital
  • Chinese University of Hong Kong-Prince of Wales Hospital
  • Zhongshan Hospital Fudan University
  • Sun Yat-sen University Cancer Center
  • Pamela Youde Nethersole Eastern Hospital
  • Centro Comprensivo de Cancer de UPR
  • National Cancer Centre Singapore
  • National Taiwan University Hospital
  • Chang Gung Hospital-Lin Kou Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Active Comparator

Experimental

Arm Label

Arm I (chemoradiation, cisplatin, fluorouracil)

Arm II (chemoradiation, gemcitabine hydrochloride, paclitaxel)

Arm III (chemoradiation, cisplatin, fluorouracil)

Arm IV (chemoradiation, observation)

Arm Description

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.

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 receive PF regimen as in Arm I of Phase II.

Patients undergo clinical observation.

Outcomes

Primary Outcome Measures

Overall survival (OS) (Undetectable Plasma EBV DNA Cohort Phase III)
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test. The confidence interval approach will be used for the final analysis of OS.
Progression-free survival (PFS) (Detectable Plasma EBV DNA Cohort Phase II)
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test. A one-sided log rank test will be used to compare the PFS at a significance level of 0.1379.

Secondary Outcome Measures

Changes in pure tone audiometry (Phase II and III)
Correlation between categorical measures will be summarized by odds ratios, chi-square tests, and associated measures. Adjusted correlation may be derived from analysis of covariance (ANCOVA) models or derived directly using nonparametric analysis of variance (ANOVA) models if normality assumption is violated. Correlations between HHIE-S PRO scores and PTA and FACT-NP hearing, and PTA will be compared as dependent statistics
Changes in QOL (hearing) as assessed by the Hearing Handicap Inventory for the Elderly-Screening version (HHIE-S) (Phase II and III)
QOL analysis including overall score and change from baseline will be summarized using mean and standard deviation at each time point for each arm. Overall and nasopharyngeal-specific QOL, hearing QOL (FACT-NP hearing domain, HHIE-S scores), peripheral neuropathy QOL over the short and long term and pure-tone audiometry (PTA) scores will be compared using a two sample independent t test and paired t test if the comparison is within the experimental arm between different time points.
Changes in QOL (peripheral neuropathy) as assessed by the FACT-Taxane (Phase II and III)
Changes in quality of life (QOL) (general and physical well-being) assessed using the Functional Assessment of Cancer Therapy (FACT)-Nasopharyngeal (NP) (Phase II and III)
Changes in patient reported outcome (PRO) scores will be correlated to clearance or non-clearance of EBV titers. Descriptive statistics derived from FACT-NP will be used to enrich the understanding of QOL as it pertains to the 2 phase III arms of observation versus additional adjuvant chemotherapy. Univariable and multivariable analysis will be performed using the Cox proportional hazards model for OS and distant metastasis. Pearson correlation will be estimated between general and physical well-being. QOL measures and change from baseline will be correlated to EBV DNA.
Cost effectiveness as assessed by the health-related QOL (HRQOL) from the EuroQol (EQ-5D) instrument (Phase II and III)
Incremental cost effectiveness ratios will be compared to determine the probability of cost effectiveness of various interventions, with sensitivity analyses to identify model weaknesses. The expected value of perfect information will be determined to delimit the upper boundary for cost-effective future investment in this area of research.
Incidence of acute grade 3-5 adverse events (Phase II and III)
Rates of specific acute toxicity profiles and late toxicity profiles will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test between the 2 treatment arms.
Incidence of death (Phase II and III)
Incidence of late grade 3-5 adverse events (Phase II and III)
Rates of specific acute toxicity profiles and late toxicity profiles will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test between the 2 treatment arms.
OS (Detectable Plasma EBV DNA Cohort Phase II)
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test.
PFS (Undetectable Plasma EBV DNA Cohort Phase III)
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test.
Time to distant metastasis (DM) (Phase II and III)
The cumulative incidence method will be used to estimate local, regional, and distant failure rates. The failure rates for the experimental treatment will be compared against the control using a failure-specific log-rank test. Multivariate analysis will be performed using the Cox proportional hazards model.
Time to local progression (Phase II and III)
The cumulative incidence method will be used to estimate local, regional, and distant failure rates. The failure rates for the experimental treatment will be compared against the control using a failure-specific log-rank test. Multivariate analysis will be performed using the Cox proportional hazards model.
Time to regional progression (Phase II and III)
Defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. The cumulative incidence method will be used to estimate local, regional, and distant failure rates. The failure rates for the experimental treatment will be compared against the control using a failure-specific log-rank test. Multivariate analysis will be performed using the Cox proportional hazards model.

Full Information

First Posted
May 7, 2014
Last Updated
September 5, 2023
Sponsor
NRG Oncology
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02135042
Brief Title
Individualized Treatment in Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 21, 2014 (Actual)
Primary Completion Date
February 2026 (Anticipated)
Study Completion Date
February 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NRG Oncology
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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.
Detailed Description
PRIMARY OBJECTIVES: 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) SECONDARY OBJECTIVES: 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) OUTLINE: 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. PHASE III: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epstein-Barr Virus Infection, Stage II Nasopharyngeal Carcinoma, Stage III Nasopharyngeal Carcinoma, Stage IVA Nasopharyngeal Carcinoma, Stage IVB Nasopharyngeal Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
676 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (chemoradiation, cisplatin, fluorouracil)
Arm Type
Active Comparator
Arm Description
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 Title
Arm II (chemoradiation, gemcitabine hydrochloride, paclitaxel)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm III (chemoradiation, cisplatin, fluorouracil)
Arm Type
Active Comparator
Arm Description
Patients receive PF regimen as in Arm I of Phase II.
Arm Title
Arm IV (chemoradiation, observation)
Arm Type
Experimental
Arm Description
Patients undergo clinical observation.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Clinical Observation
Intervention Description
Undergo clinical observation
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Other Intervention Name(s)
5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Actino-Hermal, Adrucil, Arumel, Cytosafe, Efudex, Efurix, Fiverocil, Fluoro Uracil, Fluoroplex, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Flurox, Ribofluor, Ro 2-9757, Ro-2-9757, Timazin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Gemcitabine Hydrochloride
Other Intervention Name(s)
dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
Intensity-Modulated Radiation Therapy
Other Intervention Name(s)
IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy
Intervention Description
Undergo IMRT
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Overall survival (OS) (Undetectable Plasma EBV DNA Cohort Phase III)
Description
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test. The confidence interval approach will be used for the final analysis of OS.
Time Frame
Up to 7 years
Title
Progression-free survival (PFS) (Detectable Plasma EBV DNA Cohort Phase II)
Description
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test. A one-sided log rank test will be used to compare the PFS at a significance level of 0.1379.
Time Frame
Up to 7 years
Secondary Outcome Measure Information:
Title
Changes in pure tone audiometry (Phase II and III)
Description
Correlation between categorical measures will be summarized by odds ratios, chi-square tests, and associated measures. Adjusted correlation may be derived from analysis of covariance (ANCOVA) models or derived directly using nonparametric analysis of variance (ANOVA) models if normality assumption is violated. Correlations between HHIE-S PRO scores and PTA and FACT-NP hearing, and PTA will be compared as dependent statistics
Time Frame
Baseline to up to 1 year
Title
Changes in QOL (hearing) as assessed by the Hearing Handicap Inventory for the Elderly-Screening version (HHIE-S) (Phase II and III)
Description
QOL analysis including overall score and change from baseline will be summarized using mean and standard deviation at each time point for each arm. Overall and nasopharyngeal-specific QOL, hearing QOL (FACT-NP hearing domain, HHIE-S scores), peripheral neuropathy QOL over the short and long term and pure-tone audiometry (PTA) scores will be compared using a two sample independent t test and paired t test if the comparison is within the experimental arm between different time points.
Time Frame
Baseline to up to 24 months
Title
Changes in QOL (peripheral neuropathy) as assessed by the FACT-Taxane (Phase II and III)
Time Frame
Baseline to up to 24 months
Title
Changes in quality of life (QOL) (general and physical well-being) assessed using the Functional Assessment of Cancer Therapy (FACT)-Nasopharyngeal (NP) (Phase II and III)
Description
Changes in patient reported outcome (PRO) scores will be correlated to clearance or non-clearance of EBV titers. Descriptive statistics derived from FACT-NP will be used to enrich the understanding of QOL as it pertains to the 2 phase III arms of observation versus additional adjuvant chemotherapy. Univariable and multivariable analysis will be performed using the Cox proportional hazards model for OS and distant metastasis. Pearson correlation will be estimated between general and physical well-being. QOL measures and change from baseline will be correlated to EBV DNA.
Time Frame
Baseline to up to 24 months
Title
Cost effectiveness as assessed by the health-related QOL (HRQOL) from the EuroQol (EQ-5D) instrument (Phase II and III)
Description
Incremental cost effectiveness ratios will be compared to determine the probability of cost effectiveness of various interventions, with sensitivity analyses to identify model weaknesses. The expected value of perfect information will be determined to delimit the upper boundary for cost-effective future investment in this area of research.
Time Frame
Up to 24 months
Title
Incidence of acute grade 3-5 adverse events (Phase II and III)
Description
Rates of specific acute toxicity profiles and late toxicity profiles will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test between the 2 treatment arms.
Time Frame
Up to 7 years
Title
Incidence of death (Phase II and III)
Time Frame
Up to 30 days of end of protocol treatment
Title
Incidence of late grade 3-5 adverse events (Phase II and III)
Description
Rates of specific acute toxicity profiles and late toxicity profiles will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test between the 2 treatment arms.
Time Frame
Up to 7 years
Title
OS (Detectable Plasma EBV DNA Cohort Phase II)
Description
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test.
Time Frame
Up to 7 years
Title
PFS (Undetectable Plasma EBV DNA Cohort Phase III)
Description
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test.
Time Frame
Up to 7 years
Title
Time to distant metastasis (DM) (Phase II and III)
Description
The cumulative incidence method will be used to estimate local, regional, and distant failure rates. The failure rates for the experimental treatment will be compared against the control using a failure-specific log-rank test. Multivariate analysis will be performed using the Cox proportional hazards model.
Time Frame
Up to 7 years
Title
Time to local progression (Phase II and III)
Description
The cumulative incidence method will be used to estimate local, regional, and distant failure rates. The failure rates for the experimental treatment will be compared against the control using a failure-specific log-rank test. Multivariate analysis will be performed using the Cox proportional hazards model.
Time Frame
Up to 7 years
Title
Time to regional progression (Phase II and III)
Description
Defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. The cumulative incidence method will be used to estimate local, regional, and distant failure rates. The failure rates for the experimental treatment will be compared against the control using a failure-specific log-rank test. Multivariate analysis will be performed using the Cox proportional hazards model.
Time Frame
Up to 7 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 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 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. 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: 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 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 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 the 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. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy Lee
Organizational Affiliation
NRG Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
The Kirklin Clinic at Acton Road
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35243
Country
United States
Facility Name
Banner University Medical Center - Tucson
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
Sutter Cancer Centers Radiation Oncology Services-Auburn
City
Auburn
State/Province
California
ZIP/Postal Code
95603
Country
United States
Facility Name
Alta Bates Summit Medical Center-Herrick Campus
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
Mills-Peninsula Medical Center
City
Burlingame
State/Province
California
ZIP/Postal Code
94010
Country
United States
Facility Name
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
City
Cameron Park
State/Province
California
ZIP/Postal Code
95682
Country
United States
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Kaiser Permanente Dublin
City
Dublin
State/Province
California
ZIP/Postal Code
94568
Country
United States
Facility Name
Fresno Cancer Center
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
UC San Diego Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Memorial Medical Center
City
Modesto
State/Province
California
ZIP/Postal Code
95355
Country
United States
Facility Name
Kaiser Permanente Oakland-Broadway
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
UC Irvine Health/Chao Family Comprehensive Cancer Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Palo Alto Medical Foundation Health Care
City
Palo Alto
State/Province
California
ZIP/Postal Code
94301
Country
United States
Facility Name
Stanford Cancer Institute Palo Alto
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Kaiser Permanente-Rancho Cordova Cancer Center
City
Rancho Cordova
State/Province
California
ZIP/Postal Code
95670
Country
United States
Facility Name
Rohnert Park Cancer Center
City
Rohnert Park
State/Province
California
ZIP/Postal Code
94928
Country
United States
Facility Name
Sutter Cancer Centers Radiation Oncology Services-Roseville
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
The Permanente Medical Group-Roseville Radiation Oncology
City
Roseville
State/Province
California
ZIP/Postal Code
95678
Country
United States
Facility Name
Sutter Medical Center Sacramento
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
University of California Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
South Sacramento Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95823
Country
United States
Facility Name
California Pacific Medical Center-Pacific Campus
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
UCSF Medical Center-Mount Zion
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
UCSF Medical Center-Mission Bay
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Kaiser Permanente Medical Center - Santa Clara
City
Santa Clara
State/Province
California
ZIP/Postal Code
95051
Country
United States
Facility Name
City of Hope South Pasadena
City
South Pasadena
State/Province
California
ZIP/Postal Code
91030
Country
United States
Facility Name
Kaiser Permanente Cancer Treatment Center
City
South San Francisco
State/Province
California
ZIP/Postal Code
94080
Country
United States
Facility Name
Palo Alto Medical Foundation-Sunnyvale
City
Sunnyvale
State/Province
California
ZIP/Postal Code
94086
Country
United States
Facility Name
Sutter Cancer Centers Radiation Oncology Services-Vacaville
City
Vacaville
State/Province
California
ZIP/Postal Code
95687
Country
United States
Facility Name
SCL Health Cancer Centers of Colorado - Lutheran Medical Center
City
Golden
State/Province
Colorado
ZIP/Postal Code
80401
Country
United States
Facility Name
North Colorado Medical Center
City
Greeley
State/Province
Colorado
ZIP/Postal Code
80631
Country
United States
Facility Name
McKee Medical Center
City
Loveland
State/Province
Colorado
ZIP/Postal Code
80539
Country
United States
Facility Name
Parker Adventist Hospital
City
Parker
State/Province
Colorado
ZIP/Postal Code
80138
Country
United States
Facility Name
SCL Health Lutheran Medical Center
City
Wheat Ridge
State/Province
Colorado
ZIP/Postal Code
80033
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Helen F Graham Cancer Center
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
Christiana Care Health System-Christiana Hospital
City
Newark
State/Province
Delaware
ZIP/Postal Code
19718
Country
United States
Facility Name
Baptist MD Anderson Cancer Center
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Emory Proton Therapy Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Emory University Hospital Midtown
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Emory University Hospital/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Emory Saint Joseph's Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
The Cancer Center of Hawaii-Pali Momi
City
'Aiea
State/Province
Hawaii
ZIP/Postal Code
96701
Country
United States
Facility Name
Queen's Medical Center
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
The Cancer Center of Hawaii-Liliha
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96817
Country
United States
Facility Name
Saint Alphonsus Cancer Care Center-Boise
City
Boise
State/Province
Idaho
ZIP/Postal Code
83706
Country
United States
Facility Name
Rush - Copley Medical Center
City
Aurora
State/Province
Illinois
ZIP/Postal Code
60504
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
John H Stroger Jr Hospital of Cook County
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Cancer Care Specialists of Illinois - Decatur
City
Decatur
State/Province
Illinois
ZIP/Postal Code
62526
Country
United States
Facility Name
Decatur Memorial Hospital
City
Decatur
State/Province
Illinois
ZIP/Postal Code
62526
Country
United States
Facility Name
Crossroads Cancer Center
City
Effingham
State/Province
Illinois
ZIP/Postal Code
62401
Country
United States
Facility Name
Memorial Medical Center
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62781
Country
United States
Facility Name
Carle Cancer Center
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
Memorial Hospital of South Bend
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
Iowa Methodist Medical Center
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50309
Country
United States
Facility Name
University of Iowa/Holden Comprehensive Cancer Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Ascension Via Christi Hospitals Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Wesley Medical Center
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Greater Baltimore Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
Facility Name
Johns Hopkins University/Sidney Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Saint Joseph Mercy Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
McLaren Cancer Institute-Bay City
City
Bay City
State/Province
Michigan
ZIP/Postal Code
48706
Country
United States
Facility Name
Henry Ford Cancer Institute-Downriver
City
Brownstown
State/Province
Michigan
ZIP/Postal Code
48183
Country
United States
Facility Name
Saint Joseph Mercy Canton
City
Canton
State/Province
Michigan
ZIP/Postal Code
48188
Country
United States
Facility Name
McLaren Cancer Institute-Clarkston
City
Clarkston
State/Province
Michigan
ZIP/Postal Code
48346
Country
United States
Facility Name
Henry Ford Macomb Hospital-Clinton Township
City
Clinton Township
State/Province
Michigan
ZIP/Postal Code
48038
Country
United States
Facility Name
Wayne State University/Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Weisberg Cancer Treatment Center
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Facility Name
McLaren Cancer Institute-Flint
City
Flint
State/Province
Michigan
ZIP/Postal Code
48532
Country
United States
Facility Name
Singh and Arora Hematology Oncology PC
City
Flint
State/Province
Michigan
ZIP/Postal Code
48532
Country
United States
Facility Name
Karmanos Cancer Institute at McLaren Greater Lansing
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48910
Country
United States
Facility Name
Mid-Michigan Physicians-Lansing
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48912
Country
United States
Facility Name
Sparrow Hospital
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48912
Country
United States
Facility Name
McLaren Cancer Institute-Lapeer Region
City
Lapeer
State/Province
Michigan
ZIP/Postal Code
48446
Country
United States
Facility Name
Trinity Health Saint Mary Mercy Livonia Hospital
City
Livonia
State/Province
Michigan
ZIP/Postal Code
48154
Country
United States
Facility Name
McLaren Cancer Institute-Macomb
City
Mount Clemens
State/Province
Michigan
ZIP/Postal Code
48043
Country
United States
Facility Name
McLaren Cancer Institute-Central Michigan
City
Mount Pleasant
State/Province
Michigan
ZIP/Postal Code
48858
Country
United States
Facility Name
McLaren Cancer Institute-Northern Michigan
City
Petoskey
State/Province
Michigan
ZIP/Postal Code
49770
Country
United States
Facility Name
Saint Joseph Mercy Oakland
City
Pontiac
State/Province
Michigan
ZIP/Postal Code
48341
Country
United States
Facility Name
McLaren-Port Huron
City
Port Huron
State/Province
Michigan
ZIP/Postal Code
48060
Country
United States
Facility Name
Ascension Saint Mary's Hospital
City
Saginaw
State/Province
Michigan
ZIP/Postal Code
48601
Country
United States
Facility Name
Henry Ford West Bloomfield Hospital
City
West Bloomfield
State/Province
Michigan
ZIP/Postal Code
48322
Country
United States
Facility Name
Fairview Ridges Hospital
City
Burnsville
State/Province
Minnesota
ZIP/Postal Code
55337
Country
United States
Facility Name
Minnesota Oncology - Burnsville
City
Burnsville
State/Province
Minnesota
ZIP/Postal Code
55337
Country
United States
Facility Name
Unity Hospital
City
Fridley
State/Province
Minnesota
ZIP/Postal Code
55432
Country
United States
Facility Name
Minnesota Oncology Hematology PA-Maplewood
City
Maplewood
State/Province
Minnesota
ZIP/Postal Code
55109
Country
United States
Facility Name
Abbott-Northwestern Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Hennepin County Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
North Memorial Medical Health Center
City
Robbinsdale
State/Province
Minnesota
ZIP/Postal Code
55422
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Regions Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Rice Memorial Hospital
City
Willmar
State/Province
Minnesota
ZIP/Postal Code
56201
Country
United States
Facility Name
Saint Francis Medical Center
City
Cape Girardeau
State/Province
Missouri
ZIP/Postal Code
63703
Country
United States
Facility Name
Siteman Cancer Center at West County Hospital
City
Creve Coeur
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Delbert Day Cancer Institute at PCRMC
City
Rolla
State/Province
Missouri
ZIP/Postal Code
65401
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Siteman Cancer Center-South County
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63129
Country
United States
Facility Name
Mercy Hospital Saint Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Siteman Cancer Center at Saint Peters Hospital
City
Saint Peters
State/Province
Missouri
ZIP/Postal Code
63376
Country
United States
Facility Name
Mercy Hospital Springfield
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65804
Country
United States
Facility Name
CoxHealth South Hospital
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65807
Country
United States
Facility Name
Saint James Community Hospital and Cancer Treatment Center
City
Butte
State/Province
Montana
ZIP/Postal Code
59701
Country
United States
Facility Name
Nebraska Methodist Hospital
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Radiation Oncology Centers of Nevada Central
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Facility Name
Radiation Oncology Centers of Nevada Southeast
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89119
Country
United States
Facility Name
Renown Regional Medical Center
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
Saint Mary's Regional Medical Center
City
Reno
State/Province
Nevada
ZIP/Postal Code
89503
Country
United States
Facility Name
Memorial Sloan Kettering Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Rutgers New Jersey Medical School
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07101
Country
United States
Facility Name
Montefiore Medical Center-Einstein Campus
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Medical Center - Moses Campus
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
New York-Presbyterian/Brooklyn Methodist Hospital
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11215
Country
United States
Facility Name
Maimonides Medical Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11219
Country
United States
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Laura and Isaac Perlmutter Cancer Center at NYU Langone
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
New York Proton Center
City
New York
State/Province
New York
ZIP/Postal Code
10035
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Memorial Sloan Kettering Sleepy Hollow
City
Sleepy Hollow
State/Province
New York
ZIP/Postal Code
10591
Country
United States
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Facility Name
Cleveland Clinic Akron General
City
Akron
State/Province
Ohio
ZIP/Postal Code
44307
Country
United States
Facility Name
Geauga Hospital
City
Chardon
State/Province
Ohio
ZIP/Postal Code
44024
Country
United States
Facility Name
University of Cincinnati Cancer Center-UC Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic Cancer Center/Fairview Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44111
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Mercy Cancer Center-Elyria
City
Elyria
State/Province
Ohio
ZIP/Postal Code
44035
Country
United States
Facility Name
Cleveland Clinic Cancer Center Mansfield
City
Mansfield
State/Province
Ohio
ZIP/Postal Code
44906
Country
United States
Facility Name
North Coast Cancer Care
City
Sandusky
State/Province
Ohio
ZIP/Postal Code
44870
Country
United States
Facility Name
Cleveland Clinic Cancer Center Strongsville
City
Strongsville
State/Province
Ohio
ZIP/Postal Code
44136
Country
United States
Facility Name
ProMedica Flower Hospital
City
Sylvania
State/Province
Ohio
ZIP/Postal Code
43560
Country
United States
Facility Name
University of Cincinnati Cancer Center-West Chester
City
West Chester
State/Province
Ohio
ZIP/Postal Code
45069
Country
United States
Facility Name
UHHS-Westlake Medical Center
City
Westlake
State/Province
Ohio
ZIP/Postal Code
44145
Country
United States
Facility Name
Cleveland Clinic Wooster Family Health and Surgery Center
City
Wooster
State/Province
Ohio
ZIP/Postal Code
44691
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Mercy Hospital Oklahoma City
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73120
Country
United States
Facility Name
Legacy Mount Hood Medical Center
City
Gresham
State/Province
Oregon
ZIP/Postal Code
97030
Country
United States
Facility Name
Legacy Good Samaritan Hospital and Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Christiana Care Health System-Concord Health Center
City
Chadds Ford
State/Province
Pennsylvania
ZIP/Postal Code
19317
Country
United States
Facility Name
Geisinger Medical Center
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822
Country
United States
Facility Name
Geisinger Medical Oncology-Lewisburg
City
Lewisburg
State/Province
Pennsylvania
ZIP/Postal Code
17837
Country
United States
Facility Name
Lewistown Hospital
City
Lewistown
State/Province
Pennsylvania
ZIP/Postal Code
17044
Country
United States
Facility Name
Geisinger Cancer Services-Pottsville
City
Pottsville
State/Province
Pennsylvania
ZIP/Postal Code
17901
Country
United States
Facility Name
Reading Hospital
City
West Reading
State/Province
Pennsylvania
ZIP/Postal Code
19611
Country
United States
Facility Name
Geisinger Wyoming Valley/Henry Cancer Center
City
Wilkes-Barre
State/Province
Pennsylvania
ZIP/Postal Code
18711
Country
United States
Facility Name
Prisma Health Cancer Institute - Spartanburg
City
Boiling Springs
State/Province
South Carolina
ZIP/Postal Code
29316
Country
United States
Facility Name
Prisma Health Cancer Institute - Faris
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Saint Francis Cancer Center
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29607
Country
United States
Facility Name
Prisma Health Cancer Institute - Eastside
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Prisma Health Cancer Institute - Greer
City
Greer
State/Province
South Carolina
ZIP/Postal Code
29650
Country
United States
Facility Name
Gibbs Cancer Center-Pelham
City
Greer
State/Province
South Carolina
ZIP/Postal Code
29651
Country
United States
Facility Name
Prisma Health Cancer Institute - Seneca
City
Seneca
State/Province
South Carolina
ZIP/Postal Code
29672
Country
United States
Facility Name
Spartanburg Medical Center
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
Facility Name
UT Southwestern/Simmons Cancer Center-Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
American Fork Hospital / Huntsman Intermountain Cancer Center
City
American Fork
State/Province
Utah
ZIP/Postal Code
84003
Country
United States
Facility Name
Sandra L Maxwell Cancer Center
City
Cedar City
State/Province
Utah
ZIP/Postal Code
84720
Country
United States
Facility Name
Logan Regional Hospital
City
Logan
State/Province
Utah
ZIP/Postal Code
84321
Country
United States
Facility Name
Intermountain Medical Center
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
McKay-Dee Hospital Center
City
Ogden
State/Province
Utah
ZIP/Postal Code
84403
Country
United States
Facility Name
Utah Valley Regional Medical Center
City
Provo
State/Province
Utah
ZIP/Postal Code
84604
Country
United States
Facility Name
Riverton Hospital
City
Riverton
State/Province
Utah
ZIP/Postal Code
84065
Country
United States
Facility Name
Saint George Regional Medical Center
City
Saint George
State/Province
Utah
ZIP/Postal Code
84770
Country
United States
Facility Name
Utah Cancer Specialists-Salt Lake City
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
Inova Schar Cancer Institute
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Inova Fairfax Hospital
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Naval Medical Center - Portsmouth
City
Portsmouth
State/Province
Virginia
ZIP/Postal Code
23708-2197
Country
United States
Facility Name
Legacy Salmon Creek Hospital
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98686
Country
United States
Facility Name
Langlade Hospital and Cancer Center
City
Antigo
State/Province
Wisconsin
ZIP/Postal Code
54409
Country
United States
Facility Name
HSHS Sacred Heart Hospital
City
Eau Claire
State/Province
Wisconsin
ZIP/Postal Code
54701
Country
United States
Facility Name
Marshfield Medical Center-EC Cancer Center
City
Eau Claire
State/Province
Wisconsin
ZIP/Postal Code
54701
Country
United States
Facility Name
Gundersen Lutheran Medical Center
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
University of Wisconsin Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Marshfield Medical Center-Marshfield
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States
Facility Name
Marshfield Medical Center
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Marshfield Clinic-Minocqua Center
City
Minocqua
State/Province
Wisconsin
ZIP/Postal Code
54548
Country
United States
Facility Name
Marshfield Medical Center-Rice Lake
City
Rice Lake
State/Province
Wisconsin
ZIP/Postal Code
54868
Country
United States
Facility Name
Ascension Saint Michael's Hospital
City
Stevens Point
State/Province
Wisconsin
ZIP/Postal Code
54481
Country
United States
Facility Name
Marshfield Medical Center-River Region at Stevens Point
City
Stevens Point
State/Province
Wisconsin
ZIP/Postal Code
54482
Country
United States
Facility Name
Aspirus Regional Cancer Center
City
Wausau
State/Province
Wisconsin
ZIP/Postal Code
54401
Country
United States
Facility Name
Diagnostic and Treatment Center
City
Weston
State/Province
Wisconsin
ZIP/Postal Code
54476
Country
United States
Facility Name
Marshfield Medical Center - Weston
City
Weston
State/Province
Wisconsin
ZIP/Postal Code
54476
Country
United States
Facility Name
Aspirus Cancer Care - Wisconsin Rapids
City
Wisconsin Rapids
State/Province
Wisconsin
ZIP/Postal Code
54494
Country
United States
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
London Regional Cancer Program
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
University Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
McGill University Department of Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1S6
Country
Canada
Facility Name
The Research Institute of the McGill University Health Centre (MUHC)
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3H 2R9
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Chinese University of Hong Kong-Prince of Wales Hospital
City
Shatin
State/Province
Hong Kong
Country
China
Facility Name
Zhongshan Hospital Fudan University
City
Guangdong Province
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
ZIP/Postal Code
510060
Country
China
Facility Name
Pamela Youde Nethersole Eastern Hospital
City
Chai Wan
Country
Hong Kong
Facility Name
Centro Comprensivo de Cancer de UPR
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico
Facility Name
National Cancer Centre Singapore
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
Chang Gung Hospital-Lin Kou Medical Center
City
Taoyuan
ZIP/Postal Code
33333
Country
Taiwan

12. IPD Sharing Statement

Learn more about this trial

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

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