Low Antioxidant Diet in Controlling Cachexia in Patients With Oropharyngeal Cancer Receiving Chemotherapy and Radiation Therapy

Study Overview
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Brief Summary
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RATIONALE: Eating a diet that is low in antioxidants may control cachexia in patients with oropharyngeal cancer. PURPOSE: This randomized phase I trial is studying the side effects of a low antioxidant diet in controlling cachexia in patients with oropharyngeal cancer receiving chemotherapy and radiation therapy.

Detailed Description
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OBJECTIVES: Primary Determine the safety of the antioxidant-deficient diet (ADD) in controlling cachexia in patients with oropharyngeal cancer receiving chemoradiotherapy. Secondary Determine the safety of the ADD as measured by quality of life, peripheral DNA damage, and change in body weight. Determine the effectiveness of the ADD on tumor growth and surrogate markers of tumor growth. Determine whether the ADD is effective in improving the tumor cachexia syndrome in these patients. Determine whether there is a serum metabolomic signature for the ADD. OUTLINE: This a prospective, randomized, double-blind, placebo-controlled study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients consume a standard diet 3 times a day for 8 weeks. Arm II: Patients consume an antioxidant-deficient diet (ADD) 3 times a day for 8 weeks. Patients receive replacement vitamins in week 9. All patients receive planned chemoradiotherapy in weeks 3-8. Quality of life, body composition (by dual-energy x-ray absorptiometry), weight, and resting energy expenditure (by indirect calorimetry) are assessed at baseline and at week 8. Blood samples are collected at baseline and at 8 weeks. Samples are evaluated for cytokine levels; evidence of DNA damage from peripheral blood lymphocytes; and serum signature characteristic to ADD by multinuclear MRI spectroscopy. Patients undergo a tumor biopsy in week 4 for research studies. Samples are collected and evaluated for generation of reactive oxygen species by using antibodies against oxidatively modified DNA and lipids; apoptosis using TdT-mediated dUTP nick-end labeling assay and classical morphological criteria; and levels of the tumor toxohormones lipid mobilizing factor and proteolysis inducing factor by real time-PCR, northern blotting, and western blotting methods. After completion of study therapy, patients are followed once during weeks 9-12.

Official Title
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Phase I Randomized, Double-blind, Placebo-controlled Trial of the Effect of Temporary Dietary Antioxidant Depletion on Tumor Growth and Cachexia in Head and Neck Cancer Patients Receiving Chemoradiation Therapy

Conditions
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Cachexia, Head and Neck Cancer, Weight Changes

Intervention / Treatment
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* Other: ADD
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Biopsy-proven carcinoma of the oropharynx (regardless of primary diagnosis or recurrence) No active treatment for disease within the past 4 weeks PATIENT CHARACTERISTICS: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Feeding tubes allowed Prior malignancies allowed provided all of the following criteria are met: Patient has undergone potentially curative therapy for all prior malignancies There has been no evidence of any prior malignancies within the past 5 years (except for successfully treated cervical or non-melanoma skin cancer with no evidence of recurrences) Patient is deemed by their treating physician to be at low risk for recurrence from prior malignancies Must be able to speak English Must have adequate home refrigeration No intractable vomiting No ascites or clinical/ultrasound evidence of fluid retention No uncontrolled hypertension No severe congestive heart failure No pneumonia No severe infections No known HIV positivity No coexisting medical condition that would preclude study compliance No decisionally-impaired individuals No history of abetalipoproteinemia (Bassen-Kornzweig syndrome) No history of spinocerebellar ataxia No history of chronic cholestatic hepatobiliary disease No history of diagnosed vitamin E deficiency No history of protein-energy malnutrition (marasmus or kwashiorkor) No history of disorders related to malabsorption (e.g., celiac disease, sprue, cystic fibrosis, duodenal bypass, congenital partial obstruction of the jejunum, obstruction of the bile ducts, giardiasis, or cirrhosis) No history of achlorhydria PRIOR CONCURRENT THERAPY: See Disease Characteristics No concurrent parenteral nutrition

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antioxidant-deficient diet (ADD)<br> | Other: ADD<br>* The ADD has a composition of 65% carbohydrate, 20% fat, and 15% protein. The diet will be completely depleted of vitamins A, E and beta-carotene; it will have 10 mg of vitamin C (6.5% of RDA) added per person per day<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Jevity 1.5 (1.5 cal/mL) will be used for the placebo patients in this study. This will simulate the standard of care for patients not on the ADD. Jevity 1.5 is an isotonic, fiber-fortified, high-nitrogen liquid formula providing complete, balanced nutrition for patients requiring short- or long-term tube feeding, given once per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of people with adverse events | Estimate the safety of the antioxidant-deficient diet (ADD) by measuring the frequency of grade 3 or 4 adverse events, per CTCAE criteria | 70 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cachexia, weight changes, recurrent oropharyngeal cancer, stage I oropharyngeal cancer, stage II oropharyngeal cancer, stage III oropharyngeal cancer, stage IV oropharyngeal cancer