Radiation Therapy, Amifostine, and Chemotherapy in Treating Young Patients With Newly Diagnosed Nasopharyngeal Cancer

Phase 3

Completed

• Conditions: Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage II Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage I Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage I Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
• Interventions: Drug: Amifostine; Other: Laboratory Biomarker Analysis; Drug: Cisplatin; Radiation: Radiation Therapy; Drug: Fluorouracil

• Registration Number: NCT00274937
• Lead Sponsor: Children's Oncology Group

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.

Study Timeline

• Study First Submitted: 2006-01-10
• Study First Submitted QC: 2006-01-10
• Study First Posted: 2006-01-11
• Study Start: 2006-02-20
• Primary Completion: 2014-12-31
• Results First Submitted: 2016-10-24
• Results First Submitted QC: 2016-11-23
• Results First Posted: 2017-01-19
• Study Completion: 2022-09-30
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-03
• Last Update Posted: 2022-10-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 111

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Stratum I (radiotherapy, chemoprotective agent)	Laboratory Biomarker Analysis	Patients undergo radiotherapy 5 days a week for 8 weeks. Patients also receive amifostine subcutaneously on the same days they undergo radiotherapy.
Stratum I (radiotherapy, chemoprotective agent)	Radiation Therapy	Patients undergo radiotherapy 5 days a week for 8 weeks. Patients also receive amifostine subcutaneously on the same days they undergo radiotherapy.
Stratum II (chemotherapy, chemoprotective agent, radiotherapy)	Laboratory Biomarker Analysis	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 weeks 10-18, patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive 3 courses of cisplatin as before.
Stratum II (chemotherapy, chemoprotective agent, radiotherapy)	Radiation Therapy	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 weeks 10-18, patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive 3 courses of cisplatin as before.
Stratum I (radiotherapy, chemoprotective agent)	Amifostine	Patients undergo radiotherapy 5 days a week for 8 weeks. Patients also receive amifostine subcutaneously on the same days they undergo radiotherapy.
Stratum II (chemotherapy, chemoprotective agent, radiotherapy)	Amifostine	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 weeks 10-18, patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive 3 courses of cisplatin as before.
Stratum II (chemotherapy, chemoprotective agent, radiotherapy)	Cisplatin	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 weeks 10-18, patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive 3 courses of cisplatin as before.
Stratum II (chemotherapy, chemoprotective agent, radiotherapy)	Fluorouracil	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 weeks 10-18, patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive 3 courses of cisplatin as before.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
Prognostic Significance of EBV Viral Load	At study enrollment	Viral load in blood.
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.

Trial Locations

Locations (109)

Children's Hospital of Alabama; 🇺🇸 Birmingham, Alabama, United States

University of Alabama at Birmingham Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Banner University Medical Center - Tucson; 🇺🇸 Tucson, Arizona, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Kaiser Permanente Downey Medical Center; 🇺🇸 Downey, California, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Mattel Children's Hospital UCLA; 🇺🇸 Los Angeles, California, United States

UCLA / Jonsson Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Valley Children's Hospital; 🇺🇸 Madera, California, United States

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