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

Sponsor

UNC Lineberger Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00486304

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

26.9

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cachexia Head and Neck Cancer Weight Changes	Other: ADD Other: Placebo	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Supportive Care

Official Title:

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

Study Start Date :

Feb 1, 2006

Actual Primary Completion Date :

Feb 1, 2007

Actual Study Completion Date :

May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Antioxidant-deficient diet (ADD)	Other: ADD 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
Placebo Comparator: Placebo	Other: Placebo 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

Arm

Intervention/Treatment

Experimental: Antioxidant-deficient diet (ADD)

Other: ADD

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

Placebo Comparator: Placebo

Other: Placebo

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

Outcome Measures

Primary Outcome Measures

Number of people with adverse events [70 days]
Estimate the safety of the antioxidant-deficient diet (ADD) by measuring the frequency of grade 3 or 4 adverse events, per CTCAE criteria

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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