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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02135042




Registration number
NCT02135042
Ethics application status
Date submitted
7/05/2014
Date registered
9/05/2014
Date last updated
6/11/2024

Titles & IDs
Public title
Individualized Treatment in Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA
Scientific title
Randomized Phase II and Phase III Studies of Individualized Treatment for Nasopharyngeal Carcinoma Based on Biomarker Epstein Barr Virus (EBV) Deoxyribonucleic Acid (DNA)
Secondary ID [1] 0 0
NCI-2014-00635
Secondary ID [2] 0 0
NRG-HN001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epstein-Barr Virus Infection 0 0
Stage II Nasopharyngeal Carcinoma 0 0
Stage III Nasopharyngeal Carcinoma 0 0
Stage IVA Nasopharyngeal Carcinoma 0 0
Stage IVB Nasopharyngeal Carcinoma 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cisplatin
Other interventions - Clinical Observation
Treatment: Drugs - Fluorouracil
Treatment: Drugs - Gemcitabine Hydrochloride
Treatment: Other - Intensity-Modulated Radiation Therapy
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Paclitaxel
Other interventions - Quality-of-Life Assessment

Active comparator: Arm I (chemoradiation, 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: Arm II (chemoradiation, 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: Arm III (chemoradiation, cisplatin, fluorouracil) - Patients receive PF regimen as in Arm I of Phase II.

Experimental: Arm IV (chemoradiation, observation) - Patients undergo clinical observation.


Treatment: Drugs: Cisplatin
Given IV

Other interventions: Clinical Observation
Undergo clinical observation

Treatment: Drugs: Fluorouracil
Given IV

Treatment: Drugs: Gemcitabine Hydrochloride
Given IV

Treatment: Other: Intensity-Modulated Radiation Therapy
Undergo IMRT

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Paclitaxel
Given IV

Other interventions: Quality-of-Life Assessment
Ancillary studies
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival (OS) (Undetectable Plasma EBV DNA Cohort Phase III)
Timepoint [1] 0 0
Up to 7 years
Primary outcome [2] 0 0
Progression-free survival (PFS) (Detectable Plasma EBV DNA Cohort Phase II)
Timepoint [2] 0 0
Up to 7 years
Secondary outcome [1] 0 0
Changes in pure tone audiometry (Phase II and III)
Timepoint [1] 0 0
Baseline to up to 1 year
Secondary outcome [2] 0 0
Changes in QOL (hearing) as assessed by the Hearing Handicap Inventory for the Elderly-Screening version (HHIE-S) (Phase II and III)
Timepoint [2] 0 0
Baseline to up to 24 months
Secondary outcome [3] 0 0
Changes in QOL (peripheral neuropathy) as assessed by the FACT-Taxane (Phase II and III)
Timepoint [3] 0 0
Baseline to up to 24 months
Secondary outcome [4] 0 0
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)
Timepoint [4] 0 0
Baseline to up to 24 months
Secondary outcome [5] 0 0
Cost effectiveness as assessed by the health-related QOL (HRQOL) from the EuroQol (EQ-5D) instrument (Phase II and III)
Timepoint [5] 0 0
Up to 24 months
Secondary outcome [6] 0 0
Incidence of acute grade 3-5 adverse events (Phase II and III)
Timepoint [6] 0 0
Up to 7 years
Secondary outcome [7] 0 0
Incidence of death (Phase II and III)
Timepoint [7] 0 0
Up to 30 days of end of protocol treatment
Secondary outcome [8] 0 0
Incidence of late grade 3-5 adverse events (Phase II and III)
Timepoint [8] 0 0
Up to 7 years
Secondary outcome [9] 0 0
OS (Detectable Plasma EBV DNA Cohort Phase II)
Timepoint [9] 0 0
Up to 7 years
Secondary outcome [10] 0 0
PFS (Undetectable Plasma EBV DNA Cohort Phase III)
Timepoint [10] 0 0
Up to 7 years
Secondary outcome [11] 0 0
Time to distant metastasis (DM) (Phase II and III)
Timepoint [11] 0 0
Up to 7 years
Secondary outcome [12] 0 0
Time to local progression (Phase II and III)
Timepoint [12] 0 0
Up to 7 years
Secondary outcome [13] 0 0
Time to regional progression (Phase II and III)
Timepoint [13] 0 0
Up to 7 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/04/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/02/2031
Actual
Sample size
Target
Accrual to date
Final
685
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Delaware
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Hawaii
Country [10] 0 0
United States of America
State/province [10] 0 0
Idaho
Country [11] 0 0
United States of America
State/province [11] 0 0
Illinois
Country [12] 0 0
United States of America
State/province [12] 0 0
Indiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Iowa
Country [14] 0 0
United States of America
State/province [14] 0 0
Kansas
Country [15] 0 0
United States of America
State/province [15] 0 0
Maryland
Country [16] 0 0
United States of America
State/province [16] 0 0
Massachusetts
Country [17] 0 0
United States of America
State/province [17] 0 0
Michigan
Country [18] 0 0
United States of America
State/province [18] 0 0
Minnesota
Country [19] 0 0
United States of America
State/province [19] 0 0
Missouri
Country [20] 0 0
United States of America
State/province [20] 0 0
Montana
Country [21] 0 0
United States of America
State/province [21] 0 0
Nebraska
Country [22] 0 0
United States of America
State/province [22] 0 0
Nevada
Country [23] 0 0
United States of America
State/province [23] 0 0
New Jersey
Country [24] 0 0
United States of America
State/province [24] 0 0
New York
Country [25] 0 0
United States of America
State/province [25] 0 0
Ohio
Country [26] 0 0
United States of America
State/province [26] 0 0
Oklahoma
Country [27] 0 0
United States of America
State/province [27] 0 0
Oregon
Country [28] 0 0
United States of America
State/province [28] 0 0
Pennsylvania
Country [29] 0 0
United States of America
State/province [29] 0 0
South Carolina
Country [30] 0 0
United States of America
State/province [30] 0 0
Texas
Country [31] 0 0
United States of America
State/province [31] 0 0
Utah
Country [32] 0 0
United States of America
State/province [32] 0 0
Virginia
Country [33] 0 0
United States of America
State/province [33] 0 0
Washington
Country [34] 0 0
United States of America
State/province [34] 0 0
Wisconsin
Country [35] 0 0
Canada
State/province [35] 0 0
Alberta
Country [36] 0 0
Canada
State/province [36] 0 0
Ontario
Country [37] 0 0
Canada
State/province [37] 0 0
Quebec
Country [38] 0 0
China
State/province [38] 0 0
Hong Kong
Country [39] 0 0
China
State/province [39] 0 0
Shanghai
Country [40] 0 0
China
State/province [40] 0 0
Guangzhou
Country [41] 0 0
Hong Kong
State/province [41] 0 0
Chai Wan
Country [42] 0 0
Puerto Rico
State/province [42] 0 0
San Juan
Country [43] 0 0
Singapore
State/province [43] 0 0
Singapore
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taipei
Country [45] 0 0
Taiwan
State/province [45] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Other
Name
NRG Oncology
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02135042
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nancy Lee
Address 0 0
NRG Oncology
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02135042