High-Dose Radiation Therapy Plus Chemotherapy in Treating Patients With Advanced Nose or Throat Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining high-dose radiation with chemotherapy may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining high-dose radiation therapy with chemotherapy in treating patients who have newly diagnosed stage II, stage III, or stage IV nasopharyngeal cancer.

Detailed Description
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OUTLINE: Cohorts of 10 patients receive the following treatment to assess for dose-limiting toxicity. Phase I Radiotherapy: Patients receive radiotherapy once daily 5 days a week for 6 weeks beginning on day 1. Concurrent chemotherapy: Patients receive cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Adjuvant chemotherapy: Approximately 2-5 weeks after the completion of radiotherapy, patients receive fluorouracil IV continuously on days 1-4 and cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. In the absence of dose-limiting toxicity in 1 whole cohort of patients, study proceeds to phase II. Phase II Patients are treated as in phase I. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

Official Title
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Phase I/II Study of Dose-Painting Using Intensity Modulated Radiation Therapy Plus Chemotherapy in Patients With Stage II-IVB Nasopharyngeal Carcinoma

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: fluorouracil
* Procedure: adjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed nasopharyngeal cancer Stage II-IVB Newly diagnosed No distant metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 60-100% Life expectancy Not specified Hematopoietic WBC at least 3,000/mm^3 Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 8 g/dL Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN AST no greater than 2.5 times ULN Renal Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min Calcium no greater than 11.5 mg/dL Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Medically able to tolerate a definitive course of radiotherapy and the necessary immobilization No other active malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for this diagnosis More than 3 years since other prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy for this diagnosis More than 3 years since other prior radiotherapy No prior radiotherapy to the head and neck region Surgery Not specified

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-Dose Radiation Therapy Plus Chemotherapy<br>Phase I Radiotherapy: Patients receive radiotherapy once daily 5 days a week for 6 weeks beginning on day 1. Concurrent chemotherapy: Patients receive cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Adjuvant chemotherapy: Approximately 2-5 weeks after the completion of radiotherapy, patients receive fluorouracil IV continuously on days 1-4 and cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. In the absence of dose-limiting toxicity in 1 whole cohort of patients, study proceeds to phase II. Phase II Patients are treated as in phase I. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter. | Drug: cisplatin<br> <br> Drug: fluorouracil<br> <br> Procedure: adjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival Rate of Patients | Patients will be followed indefinitely and will have standard screening for development of distant metastases, including physical exam, as well as liver function tests and a chest radiograph annually. Patients will be classified as progression free as long as they remain alive with local, regional or distant recurrence. | up to 77 months | 
| Local Control of Participants | Patients will be classified as controlled as long as there is no clinical or radiographic evidence of disease progression. Physical exam with fiberoptic nasopharyngoscopy will be performed approximately every 3 months in the first year of follow-up, every 4 months in the second year, every 6 months in the third-fifth years and annually, thereafter. | every 3 months in the first year of follow-up, every 4 months in the second year, every 6 months in the third-fifth years and annually, thereafter. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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