Combination Chemotherapy and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy works in treating patients with locally advanced head and neck cancer. The doctor also wants to find out if patients who receive this treatment need a feeding tube 1 year after starting treatment.

Detailed Description
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OBJECTIVES: Primary Determine feeding tube dependency at 12 months in patients with locally advanced head and neck cancer treated with induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil followed by cisplatin and reduced-dose radiotherapy. Secondary Determine the progression-free, disease-free, and overall survival of patients treated with this regimen. Determine the pattern of failure in patients treated with this regimen. Evaluate the quality of life of patients treated with this regimen. Assess pre- and post-treatment swallowing ability of patients and the impact on their quality of life. Tertiary Quantify salivary flow rates of patients receiving chemotherapy with radiotherapy for head and neck malignancy. Evaluate the quality of saliva by examining total protein concentrations. Quantify proangiogenic cytokines (interleukin [IL]-1, IL-6, IL-8, and vascular endothelial growth factor) in the saliva of these patients. Determine the degree of mucositis and xerostomia of patients receiving chemotherapy with radiotherapy for head and neck malignancy. Compare salivary flow rates with the grade of mucositis and xerostomia of patients receiving chemotherapy with radiotherapy for head and neck malignancy. OUTLINE: This is a pilot study. Induction therapy: Patients receive docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 followed by fluorouracil IV continuously on days 1- 4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 5-14 or pegfilgrastim SC on day 5. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a partial or clinical complete response proceed to chemoradiotherapy 3 weeks later. Chemoradiotherapy: Patients receive cisplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent reduced-dose radiotherapy 5 days a week for 6 weeks. Surgery: Approximately 6 to 8 weeks after completing chemoradiotherapy, patients with residual neck disease or disease initially staged at N2 or greater undergo neck dissection. Saliva is collected periodically to measure flow rates and quality; quantify proangiogenic cytokines (interleukin [IL]-1, IL-6, IL-8 and vascular endothelial growth factor); and examine the grade of mucositis and xerostomia. Quality of life is assessed at baseline, before chemoradiotherapy, 1 month after the last radiation treatment, every 3 months for 1 year, and then every 6 months for 1 year. After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter. PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Official Title
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Phase II Pilot Study of TPF (Docetaxel, Cisplatin, and 5-FU) Induction Chemotherapy Followed by Concurrent Cisplatin and Reduced Dose Radiation in Locally Advanced Head and Neck Cancer

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: filgrastim
* Biological: pegfilgrastim
* Drug: cisplatin
* Drug: docetaxel
* Drug: fluorouracil
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed squamous cell carcinoma of the head and neck Stage IVA or IVB disease Stage III disease allowed provided patient may benefit from organ preservation or patient refused surgery Measurable or evaluable disease ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Creatinine ≤ 1.5 mg/dL OR glomerular filtration rate ≥ 60 mL/min Bilirubin normal Alkaline phosphatase (AP) and AST or ALT must be within the following ranges: AP normal AND AST or ALT ≤ 5 times upper limit of normal (ULN) AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN AP ≤ 5 times ULN AND AST or ALT normal Exclusion Criteria: Salivary gland, sinus, or nasopharyngeal primary disease Evidence of distant metastatic disease Pregnant or nursing Positive pregnancy test (Fertile patients must use effective contraception during study treatment and for 3 months after completion of study treatment) Other malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other malignancy in which stage and nature of disease is such that it is unlikely to affect survival for the next 3 years Peripheral neuropathy ≥ grade 2 Hearing loss ≥ grade 2 Severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 and/or cisplatin or other platinum analogs Poor nutritional status, in the opinion of the investigator Active infection Active ischemic heart disease Myocardial infarction within the past 6 months Prior radiotherapy above the clavicles Prior chemotherapy Prior surgery to the primary tumor except biopsy Concurrent amifostine or other investigational agents

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy + Low Dose Radiation<br>Patients receiving chemotherapy and Low Dose (60 Gy) Radiation per protocol. | Biological: filgrastim<br>* subcutaneously on Days 5-14, repeating every 3 weeks for 2 courses.<br>* Other names: Neupogen;Biological: pegfilgrastim<br>* If applicable on day 5, repeating every 3 weeks for 2 courses.<br>* Other names: Neulasta, G-CSF;Drug: cisplatin<br>* Intravenous over 1 hour on day 1, every 3 weeks for 3 courses.<br>* Other names: Platinol AQ;Drug: docetaxel<br>* Intravenous over 1 hour on day 1.<br>* Other names: Taxotere(R);Drug: fluorouracil<br>* Intravenous continuously on days 1-4.<br>* Other names: Adrucil;Procedure: conventional surgery<br>* As appropriate, neck dissection.<br>* Other names: surgery;Radiation: radiation therapy<br>* 60 Gy 5 days/week x 6 weeks with cisplatin<br>* Other names: radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Feeding Tube Dependency | All patients were non-evaluable and study was terminated early. There is no measure of outcome. | at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days With Progression-free Survival | All patients were non-evaluable and study was terminated early. There is no measure of outcome. Utilizing RECIST criteria. | Between date of registration to date of first treatment failure or death. | 
| Number of Days - Overall Survival | All patients were non-evaluable and study was terminated early. There is no measure of outcome. Utilizing RECIST criteria. | Between date of registration to date of death. | 
| Number of Days With Disease Free Survival | All patients were non-evaluable and study was terminated early. There is no measure of outcome. RECIST criteria measurement. | From Date of Registration to Date of First Treatment Failure or Death | 
| Time to Treatment Failure | All patients were non-evaluable and study was terminated early. There is no measure of outcome. Measure using RECIST criteria. | Number of Days from Complete or Partial Response to First Date of Recurrence or Progression | 
| Swallowing Ability - Quality of Life Scores | All patients were non-evaluable and study was terminated early. There is no measure of outcome. Utilizing Swallowing Portion of ASHA Functional Communication Measure for Swallowing (FCM) and Dysphagia Outcome and Severity Scale (DOSS). | Baseline, before chemoradiation, 30 days after last radiation treatment, every 3 months for the first year, then every 6 months for year 2. | 
| Quality of Life (QOL) by Functional Assessment of Cancer Therapy-H&N QOL Questionnaire | All patients were non-evaluable and study was terminated early. There is no measure of outcome. | baseline, before chemoradiotherapy, 1 month after the last radiation treatment, every 3 months for 1 year, and then every 6 months for 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oral complications of radiation therapy, oral complications of chemotherapy, mucositis, xerostomia, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx