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

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00486304
• Other study ID #: LCCC 0523
• Secondary ID: CDR0000549772
• Status: Completed
• Phase: Phase 1
• First received: June 13, 2007
• Last updated: April 16, 2012
• Start date: February 2006
• Est. completion date: May 2008

Study information

• Verified date: April 2012
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: May 2008
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Body Weight Changes
• Cachexia
• Head and Neck Cancer
• Head and Neck Neoplasms
• Weight Changes

Intervention

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
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

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes