EVALUATION OF AMIFOSTINE FOR MUCOSAL AND HEMOPOETIC PROTECTION AND CARBOPLATIN, TAXOL, RADIOTHERAPY IN THE MANAGEMENT OF PATIENTS WITH HEAD AND NECK CANCER.(GCC 0202)

Study Overview
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Brief Summary
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Purpose of this study: There is some evidence that the best treatment for head and neck cancer involves a combination of radiation therapy and chemotherapy. Radiation therapy is a form of cancer treatment using high energy x-rays. Chemotherapy is a form of cancer treatment that uses special medications. This study uses two chemotherapy drugs (Taxol and Carboplatin), which are FDA approved for treating head and neck cancers. This treatment combination has been associated with difficulty, pain, or a burning sensation upon swallowing (called esophagitis), and decrease in blood cells (cells in the blood which fight against infection). The purpose of this study is to investigate whether the addition of another drug, Amifostine, can reduce the side effects of current combination treatment (radiation and chemotherapy which is standard of care). The addition of Amifostine is the investigational part of the study. The research study is also looking at the side effects of Amifostine and cancer's growth response to this combination treatment.

Detailed Description
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Patients presenting with locally advanced squamous cell carcinomas of head and neck (SCCHN) continue to represent a significant therapeutic challenge. The bulk of tumor burden often proves to be overwhelming for conventional radiotherapy. Attempts to improve upon these poor outcomes have led investigators to explore several new strategies, one such being chemoradiation. One of the trials conducted at the University of Maryland with carboplatin and paclitaxel with daily radiation showed 82% CR at the primary site. But the most commonly encountered grade 3 toxicities were mucositis (70%), leukopenia (30%) and 3% grade 4 leukopenia. Amifostine: An organic thiophosphate is radioprotective and has shown to protect experimental animals from lethal doses of radiation. Clinical trials have demonstrated that amifostine can provide protection against the hematological toxicities and mucositis seen with various chemotherapeutic agents. Theoretically, drug interactions between amifostine and chemotherapeutic agents are not likely to occur, due to amifostine¿s rapid clearance from plasma (90% of the drug is cleared within 6 minutes). A promising venue would be the investigation of amifostine¿s role in reducing the toxicities associated with chemoradiation (which is standard of care of treating squamous cell carcinomas of head and neck). Principal objectives of the study: Primary: To evaluate whether the addition of the radioprotector amifostine can reduce the incidence and severity of mucositis and hematological toxicities caused by chemoradiation. Secondary: 1.To determine the toxicities of amifostine given in this setting. 2. To determine the response rate of this regimen in the population.

Official Title
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A SINGLE SITE EVALUATION OF AMIFOSTINE FOR MUCOSAL AND HEMOPOETIC PROTECTION AND CONCURRENT CARBOPLATIN, TAXOL, RADIOTHERAPY IN THE MANAGEMENT OF PATIENTS WITH ADVANCED LOCOREGIONAL SQUAMOUS CELL CARCINOMAS OF THE HEAD AND NECK.

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Amifostine
* Drug: Carboplatin
* Drug: Taxol
* Device: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proved locally advanced squamous cell carcinoma of the head and neck of all primary sites. The following TNM stages by sites will be eligible. Oral cavity, Pharynx, Larynx, Nasopharynx, paranasal sinuses: T4 N0-3, A,B,C T3 N1-3 A,B,C any T, N3 A,B,C Unknown primary: Tx, N3 A,B,C Note: Only clearly unresectable T4 N0 lesions are eligible for study provided the reasons for unresectability are due to extensive anatomic involvement and are outlined by the surgeon. Karnofsky performance status of 70% or better at screen and on first day of treatment. Patients with loco-regional recurrences from any site with no prior radiation therapy and not amenable for salvage surgery are eligible for study. No evidence of distant metastatic disease. No previous radiation therapy No previous chemotherapy. Adequate renal & bone marrow function determined by the following laboratory parameters. WBC 3500/ul or higher Platelet count 100.000/ul or higher Hemoglobin 9.0 g/dl or higher BUN 25 mg/dl or less, and Screatinine 2.0 mg/dl or less Total bilirubin less than 2.0 mg/dl, AST/ALT less than 3 times the ULN Creatinine Clearance 50 cc/min or higher Evidence of measurable disease. No evidence of concomitant malignancy except for non-melanomatous skin cancer (controlled or controllable) or carcinoma in situ of the cervix. Signed informed consent. No concomitant life threatening or uncontrolled serious medical illness such as end stage congestive heart failure cardiac arrythmia, liver disease and organic brain syndrome. Age 18 years or older. Exclusion Criteria: Preexisting clinically significant neuropathy. Patients currently taking antiarrhythmic medications are excluded. History of poorly-controlled hypertension, angina, arrhythmias, or a history within the past 6 months of myocardial infarction or acute congestive heart failure. Requirement for concurrent use of pilocarpine. Treatment with any investigational drugs within 4 weeks of study entry. Pregnant or lactating females or females of child bearing potential not employing adequate contraception.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMIFOSTINE +CARBOPLATIN, TAXOL +RT<br>EVALUATION OF AMIFOSTINE FOR MUCOSAL AND HEMOPOETIC PROTECTION AND CARBOPLATIN, TAXOL, RADIOTHERAPY IN THE MANAGEMENT OF PATIENTS WITH HEAD AND NECK CANCER. | Drug: Amifostine<br>* Amifostine will be given at dose of 500 mg IV within one hour before radiation<br>Drug: Carboplatin<br>* Carboplatin for 100 mg/m2 and will be administered after the taxol infusion<br>Drug: Taxol<br>* Taxol will be given at a dose of 40 mg/m2 as a 3 hour infusion dose<br>Device: Radiotherapy<br>* Radiation will be given at a dose of 1.8 Gy. for a total of 70.2 Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Mucositis and Hematological Toxicities With the Addition of Radioprotector Amifostine | Blood work (CMP was collected and evaluated for neutropenia, leukopenia and anemia) is taken prior to chemotherapy administration. The toxicity levels were measured using Common Terminology Criteria for Adverse Events (CTCAE 3.0) and monitored based on the dose of Amifostine given. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rates Based on the Study Regimen | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck cancer