Carboplatin, Capecitabine, and Radiation Therapy in Treating Patients With Stage III or Stage IV Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as carboplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of capecitabine when given together with carboplatin followed by radiation therapy in treating patients with stage III or stage IV head and neck cancer.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose (MTD) of capecitabine when administered with carboplatin as induction chemotherapy in patients with stage III-IVB squamous cell carcinoma of the head and neck. Determine the MTD of capecitabine when administered with concurrent carboplatin and intensity-modulated radiotherapy in these patients. Determine the toxicity of this regimen in these patients. Secondary Determine, preliminarily, tumor response in patients treated with this regimen. Determine the quality of life of patients treated with this regimen. OUTLINE: This is a dose-escalation study of capecitabine. Induction chemotherapy: Patients receive carboplatin IV on days 1, 8, 15, 22, 29, and 36 and oral capecitabine twice daily on days 1-14 and 22-35. Concurrent chemoradiotherapy: Beginning 2 weeks after completion of induction chemotherapy, patients receive carboplatin and capecitabine as in induction chemotherapy. Patients also undergo intensity-modulated radiotherapy (IMRT) once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33 and non-IMRT boost once daily on days 36-40 and 43-47. Treatment continues in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks after completion of concurrent chemoradiotherapy, patients who achieve a clinical complete response or who are medically operable with resectable persistent or recurrent disease undergo neck dissection (salvage surgery). Cohorts of 3-6 patients receive escalating doses of capecitabine (during both induction chemotherapy and concurrent chemoradiotherapy) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Quality of life is assessed at baseline, after completion of induction chemotherapy, and then at 1 week and 3, 6, and 12 months after completion of concurrent chemoradiotherapy. After completion of study therapy, patients are followed monthly for 3 months and then every 3 months for 1 year. PROJECTED ACCRUAL: Approximately 6-48 patients will be accrued for this study.

Official Title
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Phase I Trial of Induction Paraplatin® and Xeloda® Followed by Concurrent Paraplatin and Xeloda With Intensity Modulated Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: carboplatin
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the head and neck, including 1 of the following types: Oral cavity Oropharynx Hypopharynx Clinical stage III-IVB (T2-T4, N0-N3, M0) disease Measurable disease by physical exam, endoscopy, and/or CT scan or MRI Residual measurable disease after fine needle aspiration, core needle biopsy, or incisional or excisional biopsy of the primary tumor No evidence of distant metastases (M1) PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count > 1,500/mm^3 Platelet count > 100,000/mm^3 Hemoglobin > 9 g/dL No uncontrolled coagulopathy Hepatic AST < 2 times normal Alkaline phosphatase < 2 times normal Bilirubin normal Renal Creatinine < 2.0 mg/dL OR Creatinine clearance > 50 mL/min Cardiovascular No congestive heart failure No symptomatic coronary artery disease No uncontrolled cardiac arrhythmias No myocardial infarction within the past year No other clinically significant cardiac disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 30 days after completion of study treatment Nutritional and general physical condition must be compatible with proposed study treatment Mentally reliable No pre-existing peripheral neuropathy > grade 1 No history of hypersensitivity to fluorouracil, capecitabine, or carboplatin No active infection No other malignancy within the past 5 years except nonmelanoma skin cancer No major medical, psychiatric, or neurologic illness that would preclude study participation or giving informed consent PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy More than 5 years since prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy for head and neck tumor No prior radiotherapy to the region of planned study radiotherapy fields Surgery Recovered from prior surgery No unhealed surgical wounds Other More than 4 weeks since prior investigational drugs No concurrent warfarin, diphenylhydantoin, or fluconazole unless willing to undergo careful monitoring and appropriate dose adjustments

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: capecitabine|nan|
|Drug: carboplatin|nan|
|Procedure: conventional surgery|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx