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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00274937
First received: January 10, 2006
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Stage I Lymphoepithelioma of the Nasopharynx
Stage I Squamous Cell Carcinoma of the Nasopharynx
Stage II Lymphoepithelioma of the Nasopharynx
Stage II Squamous Cell Carcinoma of the Nasopharynx
Stage III Lymphoepithelioma of the Nasopharynx
Stage III Squamous Cell Carcinoma of the Nasopharynx
Stage IV Lymphoepithelioma of the Nasopharynx
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Drug: amifostine trihydrate
Drug: fluorouracil
Drug: cisplatin
Other: laboratory biomarker analysis
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Childhood Nasopharyngeal Carcinoma With Neoadjuvant Chemotherapy and Concomitant Chemoradiotherapy: A Groupwide Phase III Study

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Disease-free survival (EFS) [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
    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%. Confidence intervals for the estimated two year EFS will be provided. The one-sample one-sided log-rank test comparing the observed data with the hypothesized model of size 0.05 will be used to assess whether the data are consistent with the target model. The method of Lan and DeMets will be used to derive the p-values for testing procedure.


Secondary Outcome Measures:
  • Predictive value of Epstein-Barr virus (EBV) DNA as measured by quantitative detection at 2 years after treatment [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  • Prognostic significance of EBV viral load [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    The assessment of the prognostic significance of EBV changes and risk for clinical events will be conducted using survival analysis techniques.

  • Predictive value of the detection of EBV DNA in the peripheral blood [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: At baseline and up to 12 weeks after completion of radiotherapy ] [ Designated as safety issue: No ]
    The difference in the total amount of saliva collected at study enrollment will be subtracted from the total amount of saliva collected at the end of treatment, after adjustment for the collection time at each time point. A Wilcoxon test logrank test of size 0.05 of the null hypothesis of 0 median change in amount of saliva collected will be used to assess the protective effect of amifostine.


Enrollment: 111
Study Start Date: February 2006
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stratum I (radiotherapy, chemoprotective agent)
Patients undergo radiation therapy 5 days a week for 8 weeks. Patients also receive amifostine trihydrate subcutaneously on the same days they undergo radiation therapy.
Drug: amifostine trihydrate
Given subcutaneously
Other Names:
  • ethiofos
  • Ethyol
  • gammaphos
  • WR-2721
Other: laboratory biomarker analysis
Correlative studies
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Experimental: Stratum II (chemotherapy, chemoprotective agent, radiotherapy)
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 radiation therapy and receive amifostine trihydrate as in stratum I. Patients also receive 3 courses of cisplatin as before.
Drug: amifostine trihydrate
Given subcutaneously
Other Names:
  • ethiofos
  • Ethyol
  • gammaphos
  • WR-2721
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Other: laboratory biomarker analysis
Correlative studies
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation

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.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00274937

  Show 91 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Carlos Rodriguez-Galindo, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00274937     History of Changes
Other Study ID Numbers: ARAR0331, NCI-2009-00412, COG-ARAR0331, CDR0000454849, U10CA098543
Study First Received: January 10, 2006
Last Updated: February 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Nasopharyngeal Neoplasms
Head and Neck Neoplasms
Nasopharyngeal Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Pharyngeal Neoplasms
Stomatognathic Diseases
Amifostine
Cisplatin
Fluorouracil
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Radiation-Protective Agents
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014