Stage I Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7, Stage I Nasopharyngeal Undifferentiated Carcinoma AJCC v7, Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7, Stage II Nasopharyngeal Undifferentiated Carcinoma AJCC v7, Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7, Stage III Nasopharyngeal Undifferentiated Carcinoma AJCC v7, Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7, Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7
Conditions
Brief summary
This phase III trial is studying how well radiation therapy, amifostine, and chemotherapy work in treating young patients with newly diagnosed nasopharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as amifostine, may protect normal cells from the side effects of radiation therapy. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with amifostine and chemotherapy may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES: I. Determine the response rate, overall survival, and event-free survival of children with advanced nasopharyngeal carcinoma who are treated with induction chemotherapy followed by concurrent chemoradiotherapy and amifostine. SECONDARY OBJECTIVES: I. Characterize the role of Epstein-Barr virus (EBV) in the pathogenesis of nasopharyngeal carcinoma in children. II. Investigate the predictive value of the detection of EBV DNA in the peripheral blood of children with nasopharyngeal carcinoma. III. Determine the incidence of NUT rearrangements in childhood nasopharyngeal carcinoma. IV. Determine the radioprotective effect of amifostine when given daily prior to radiation therapy. OUTLINE: This is a nonrandomized, multicenter study. Patients are stratified according to stage of disease (I or IIA \[stratum I\] vs IIB-IV \[stratum II\]). STRATUM I: Patients undergo radiotherapy 5 days a week for 8 weeks. Patients also receive amifostine subcutaneously on the same days they undergo radiotherapy. STRATUM II: INDUCTION THERAPY (weeks 1-9): Patients receive cisplatin IV over 6 hours on day 1 and fluorouracil IV continuously on days 1-4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease proceed to consolidation therapy. CONSOLIDATION THERAPY (weeks 10-18): Patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive cisplatin IV over 6 hours on days 1 and 22 (2 courses). After completion of study treatment, patients are followed periodically for 10 years.
Interventions
DRUGAmifostine
Given subcutaneously
DRUGCisplatin
Given IV
DRUGFluorouracil
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
RADIATIONRadiation Therapy
Undergo radiotherapy
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
* Histological diagnosis of nasopharyngeal carcinoma WHO type II or III * Stage I-IV disease * Newly diagnosed disease * Performance status * Patients ≤ 16 years of age: Lansky 60-100% * Patients \> 16 years of age: Karnofsky 60-100% * Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min * Creatinine based on age/gender as follows: * No greater than 0.4 mg/dL (for patients 1 month to \< 6 months of age) * No greater than 0.5 mg/dL (for patients 6 months to \< 1 year of age) * No greater than 0.6 mg/dL (for patients 1-2 years of age) * No greater than 0.8 mg/dL (for patients \< 6 years of age) * No greater than 1.0mg/dL (for patients 6 to \< 10 years of age) * No greater than 1.2 mg/dL (for patients 10 to \< 13 years of age) * No greater than 1.4 mg/dL (for female patients 13 to ≥ 16 years of age) * No greater than 1.5 mg/dL (for male patients 13 to \< 16 years of age) * No greater than 1.7 mg/dL (for male patients ≥ 16 years of age) * Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age * AST or ALT \< 2.5 times ULN for age * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No prior chemotherapy or radiotherapy to the nasopharynx or neck for the treatment of nasopharyngeal carcinoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Two Year Event-free Survival (EFS) | Up to Two Year After Enrollment | The two-year event-free survival will be compared with a standard established from adult oncology data and the results of POG-9486. The two-year Kaplan-Meier estimate of event-free survival will be compared with 70% using a 1-sided test of size 0.05 using the asymptotic distribution of the complementary log-log distribution of the estimate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Predictive Value of Epstein-Barr Virus (EBV) DNA as Measured by Quantitative Detection at Enrollment on EFS 2 Years After Treatment | At study enrollment | Presence of EBV DNA in serum. |
| Prognostic Significance of EBV Viral Load | At study enrollment | Viral load in blood. |
| Predictive Value of the Detection of EBV DNA in the Peripheral Blood | Up to 6 years | The prognostic value of the presence of EBV DNA will be assessed using the log-rank test, adjusted by initial stage of disease, if appropriate. The proposed analysis will take place at the analytic endpoint of the clinical trial. |
| Protective Effects of Amifostine Assessed Primarily by Sialometry | At study enrollment | Weight of stimulated saliva production in grams. |
| Protective Effects of Amifostine Assessed Primarily by Sialometry: Weight of Unstimulated Saliva Production in Grams. | At study enrollment | Weight of unstimulated saliva production in grams. |
Countries
Australia, Canada, United States
Participant flow
Pre-assignment details
No patients were enrolled to Stratum 1.
Participants by arm
| Arm | Count |
|---|---|
| Stratum II AJCC Stage IIb - IV | 111 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 10 |
| Overall Study | Progressive Disease | 4 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Stratum II |
|---|---|
| Age, Continuous | 13.8 Participants STANDARD_DEVIATION 2.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 52 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 43 Participants |
| Region of Enrollment Australia | 1 participants |
| Region of Enrollment Canada | 2 participants |
| Region of Enrollment Saudi Arabia | 1 participants |
| Region of Enrollment United States | 107 participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 111 |
| serious Total, serious adverse events | 79 / 111 |
Outcome results
Primary
Two Year Event-free Survival (EFS)
The two-year event-free survival will be compared with a standard established from adult oncology data and the results of POG-9486. The two-year Kaplan-Meier estimate of event-free survival will be compared with 70% using a 1-sided test of size 0.05 using the asymptotic distribution of the complementary log-log distribution of the estimate.
Time frame: Up to Two Year After Enrollment
Population: No patients were enrolled to Stratum 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum II | Two Year Event-free Survival (EFS) | 0.87 Estimated probability |
Secondary
Predictive Value of Epstein-Barr Virus (EBV) DNA as Measured by Quantitative Detection at Enrollment on EFS 2 Years After Treatment
Presence of EBV DNA in serum.
Time frame: At study enrollment
Population: Data was and never will be collected.
Secondary
Predictive Value of the Detection of EBV DNA in the Peripheral Blood
The prognostic value of the presence of EBV DNA will be assessed using the log-rank test, adjusted by initial stage of disease, if appropriate. The proposed analysis will take place at the analytic endpoint of the clinical trial.
Time frame: Up to 6 years
Population: Funding was not obtained and results will never be reported.
Secondary
Prognostic Significance of EBV Viral Load
Viral load in blood.
Time frame: At study enrollment
Population: Data was and never will be collected.
Secondary
Protective Effects of Amifostine Assessed Primarily by Sialometry
Weight of stimulated saliva production in grams.
Time frame: At study enrollment
Population: Twenty-six patients in stratum 2 were evaluated at both study enrollment and at the end of consolidation for the weight of stimulated saliva production. This outcome measure was only collected for patients in Stratum 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stratum II | Protective Effects of Amifostine Assessed Primarily by Sialometry | At study Enrollment | 4.97 Grams of saliva | Standard Deviation 5.44 |
| Stratum II | Protective Effects of Amifostine Assessed Primarily by Sialometry | At end of consolidation | 3.39 Grams of saliva | Standard Deviation 4.71 |
Secondary
Protective Effects of Amifostine Assessed Primarily by Sialometry: Weight of Unstimulated Saliva Production in Grams.
Weight of unstimulated saliva production in grams.
Time frame: At study enrollment
Population: Twenty-nine patients in stratum 2 were evaluated at both study enrollment and at the end of consolidation for the weight of unstimulated saliva production. This outcome measure was only collected for patients in Stratum 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stratum II | Protective Effects of Amifostine Assessed Primarily by Sialometry: Weight of Unstimulated Saliva Production in Grams. | At study Enrollment | 3.37 Grams of saliva | Standard Deviation 4.49 |
| Stratum II | Protective Effects of Amifostine Assessed Primarily by Sialometry: Weight of Unstimulated Saliva Production in Grams. | At end of consolidation | 2.30 Grams of saliva | Standard Deviation 3.9 |