Radiation Therapy, Amifostine, and Chemotherapy in Treating Young Patients With Newly Diagnosed Nasopharyngeal Cancer - Full Text View

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:

MedlinePlus related topics: Cancer

Drug Information available for: Fluorouracil Cisplatin Amifostine Amifostine monohydrate

Genetic and Rare Diseases Information Center resources: Nasopharyngeal Carcinoma

U.S. FDA Resources

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
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

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 (Child, Adult)
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

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Carlos Rodriguez-Galindo, MD	Children's Oncology Group

More Information


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:	March 3, 2015
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Carcinoma, Squamous Cell Carcinoma Nasopharyngeal Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Squamous Cell Pharyngeal Neoplasms Otorhinolaryngologic Neoplasms Head and Neck Neoplasms Neoplasms by Site Nasopharyngeal Diseases Pharyngeal Diseases Stomatognathic Diseases	Otorhinolaryngologic Diseases Cisplatin Fluorouracil Amifostine Antineoplastic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Radiation-Protective Agents Protective Agents

ClinicalTrials.gov processed this record on September 23, 2016