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

Children's Oncology Group

Status and phase: Completed; Phase 3

Conditions: Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage II Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage I Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage I Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7

Treatments: Drug: Fluorouracil; Radiation: Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Amifostine; Drug: Cisplatin

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00274937

NCI-2009-00412 (Registry Identifier)

U10CA180886 (U.S. NIH Grant/Contract)

ARAR0331

CDR0000454849 (Other Identifier)

COG-ARAR0331 (Other Identifier)

U10CA098543 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 111 patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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111 participants in 2 patient groups

Stratum I (radiotherapy, chemoprotective agent)

Experimental group

Description:

Patients undergo radiotherapy 5 days a week for 8 weeks. Patients also receive amifostine subcutaneously on the same days they undergo radiotherapy.

Treatment:

Other: Laboratory Biomarker Analysis

Drug: Amifostine

Radiation: Radiation Therapy

Stratum II (chemotherapy, chemoprotective agent, radiotherapy)

Experimental group

Description:

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.

Treatment:

Other: Laboratory Biomarker Analysis

Drug: Cisplatin

Drug: Amifostine

Radiation: Radiation Therapy

Drug: Fluorouracil