Chemo/XRT +/- Amifostine to Assess Outcomes Related to Xerostomia, Mucositis, & Dysphagia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy 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. Amifostine may decrease the side effects caused by chemotherapy and radiation therapy. It is not yet known whether chemotherapy and radiation therapy are more effective with or without amifostine in treating head and neck cancer. PURPOSE: This randomized phase II trial is studying amifostine to see how well it works compared with standard care in reducing side effects in patients undergoing chemotherapy and radiation therapy for stage III or stage IV head and neck cancer.

Detailed Description
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OBJECTIVES: Primary To compare the incidence and severity of acute and chronic swallowing dysfunction in stage III or IV head and neck cancer patients receiving concurrent chemoradiation with or without amifostine Secondary To assess the relative incidence and severity of acute and chronic xerostomia in stage III or IV head and neck cancer patients receiving chemoradiation with or without amifostine. To assess the relative incidence and severity of mucositis and mucositis-related inflammation in stage III or IV head and neck cancer patients receiving chemoradiation with or without amifostine. To assess the effects of dysphagia, xerostomia, and mucositis-related inflammation on nutritional, physical, and functional status OUTLINE: Patients undergo intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy comprising carboplatin and paclitaxel weekly. Patients are randomized to 1 of 2 treatment arms. Arm I (standard of care): Patients are further divided into 1A or 1B. Arm IA: Standard of care plus standardized nutrition therapy (SNT) Arm IB: Standard of care plus standardized nutrition therapy plus low weight resistance training (LWRT). Arm II (amifostine): Patients are further divided into 2A or 2B. Arm IIA: Amifostine 500mg diluted in 2.9 ml injected 30-60 minutes prior to each radiation dose plus standardized nutrition therapy Arm IIB: Amifostine 500mg diluted in 2.9 ml injected 30-60 minutes prior to each radiation dose plus standardized nutrition therapy plus low weight resistance training In all arms, patients undergo swallowing function, dietary, body composition, muscle, and physical and functional performance measurements at baseline and at 1, 3, and 6 months post-therapy. Quality of life, salivary production, fatigue, and symptoms (including swallowing/eating foods, appetite, weight loss/nutrition, pain, and speech/communication) are assessed at baseline and at 1, 3, and 6 months post-therapy. Anthropometric measurements are also performed at the above time points and at mid-therapy. Blood samples and buccal rinses are collected at baseline and at 1, 3, and 6 months post-therapy for biomarker studies and for proteomic and genomic analysis by liquid chromatography and tandem mass spectrometry. After completion of study treatment, patients are followed at 1, 3, and 6 months.

Official Title
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Randomized Pilot Trial of Chemoradiation Plus or Minus Amifostine to Assess Potential Nutritional, Inflammatory and Physical Outcomes Related to Xerostomia, Mucositis and Dysphagia

Conditions
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Dysphagia, Head and Neck Cancer, Mucositis, Xerostomia

Intervention / Treatment
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* Behavioral: exercise intervention
* Drug: amifostine trihydrate
* Procedure: therapeutic dietary intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age greater than 21 Biopsy proven stage 3 or 4 squamous cell carcinoma of the larynx, pharynx, oral cavity or salivary glands No prior history of active cancer within three years other than non-melanoma skin cancer, early stage prostate or early stage cervical cancer controlled co-morbid disease ECOG PS of 0-3 Plan for definitive or post-operative CCR within 4 weeks Written informed consent Working telephone May have received prior induction chemotherapy Agree to use only study supplied liquid nutrition supplements or dietary supplements, for per os or feeding tube intake Exclusion Criteria Diagnosed HIV or AIDS History of ETOH or drug abuse within 3 months Pregnant or lactating On steroid medication or prescribed NSAIDs Consuming specialty nutrition supplements containing additional amounts of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) On orexigenic (appetite stimulant) medication. Uncontrolled comorbid disease defined as: a) severe cardiac disease Class III or greater; b) blood pressure > 160/95; c) uncontrolled pain Does not have working telephone.

Ages Eligible for Study
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Minimum Age: 21 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm IA<br>Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction. | Procedure: therapeutic dietary intervention<br>* Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction.<br>|
| Active Comparator: Arm IB<br>Patients undergo SNT and low weight resistance training (LWRT). | Behavioral: exercise intervention<br>* Patients undergo low weight resistance training.<br>Procedure: therapeutic dietary intervention<br>* Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction.<br>|
| Experimental: Arm IIA<br>Patients receive amifostine subcutaneously (SC) 30-60 minutes prior to each dose of intensity-modulated radiotherapy (IMRT). Patients also undergo SNT as in arm IA. | Drug: amifostine trihydrate<br>* Given subcutaneously<br>* Other names: Ethyol;Procedure: therapeutic dietary intervention<br>* Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction.<br>|
| Experimental: Arm IIB<br>Patients receive amifostine SC 30-60 minutes prior to each dose of IMRT. Patients also undergo SNT and LWRT as in arm IB. | Behavioral: exercise intervention<br>* Patients undergo low weight resistance training.<br>Drug: amifostine trihydrate<br>* Given subcutaneously<br>* Other names: Ethyol;Procedure: therapeutic dietary intervention<br>* Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Each Degree of Swallowing Dysfunction | Grade of swallowing dysfunction as measured by the modified barium swallow score: grade 1, normal; grade 2, within functional limits; grade 3, mild impairment; grade 4, mild to moderate impairment; grade 5, moderate impairment; grade 6, moderate to severe impairment; grade 7, severe impairment | 6 months after concurrent chemotherapy and radiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stimulated and Unstimulated Salivary Production | Unstimulated and stimulated salivary production, measured in mL/minute. Unstimulated salivary production is determined by expectoration of passively accumulated secretions accumulated in three 2-minute periods. Stimulated salivary production is determined by chewing paraffin wax with expectoration of passively accumulated secretions accumulated in three 2-minute periods. | 6 months after concurrent chemotherapy and radiation | 
| Number of Patients With Oral Mucositis by Grade | Measured by Common Toxicity Criteria (CTC) v. 3.00 = no mucositis (minimum score), 1 = mild mucositis, 2 = moderate mucositis, 3 = severe mucositis, 4 = life-threatening, disabling mucositis, 5 = death (worst score). | 6 months after concurrent chemotherapy and radiation | 
| Changes in the Amount and Texture of Food Consumed | Patients are asked to note their food intake in terms of amount and texture over the past 24 hours as measured by 24-hour dietary recalls. | at baseline, at 1 month, 3 months and 6 months post-chemoradiation | 
| Changes in the Frequency and Types of Dietary Intakes | Patients are asked to note their food intake in terms of amount and texture over the past 24 hours as measured by 24 hour dietary recalls. | at baseline, at 1 month, 3 months and 6 months post-chemoradiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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xerostomia, mucositis, dysphagia, radiation toxicity, chemotherapeutic agent toxicity, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx, recurrent verrucous carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage III verrucous carcinoma of the oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage IV verrucous carcinoma of the oral cavity, recurrent squamous cell carcinoma of the lip and oral cavity, recurrent verrucous carcinoma of the oral cavity, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, recurrent squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, salivary gland squamous cell carcinoma, stage III salivary gland cancer, stage IV salivary gland cancer, recurrent salivary gland cancer