Donepezil and Vitamin E to Prevent Side Effects Caused By Radiation Therapy to the Head in Patients Receiving Treatment for Small Cell Lung Cancer - Full Text View

Sponsors and Collaborators:	North Central Cancer Treatment Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00006349

Purpose

RATIONALE: Donepezil and vitamin E may be able to decrease side effects caused by radiation therapy given to prevent brain metastases in patients with small cell lung cancer. It is not yet known if donepezil and vitamin E are effective in preventing side effects caused by radiation therapy to the head.

PURPOSE: Randomized phase III trial to determine the effectiveness of donepezil and vitamin E in preventing side effects caused by radiation therapy given to prevent brain metastases in patients who have small cell lung cancer.

Condition	Intervention	Phase
Delirium Depression Lung Cancer Psychosocial Effects/Treatment Quality of Life Radiation Toxicity	Dietary Supplement: vitamin E Drug: donepezil hydrochloride Procedure: quality-of-life assessment	Phase III

Study Type:	Interventional
Study Design:	Supportive Care, Randomized, Double-Blind, Placebo Control
Official Title:	An Exploratory Trial of Donepezil and Vitamin E to Prevent Cognitive Dysfunction in Patients With Small Cell Lung Cancer (SCLC) After Cancer Treatment Which Includes Prophylatic Cranial Irradiation (PCI)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Depression Lung Cancer Radiation Therapy

Drug Information available for: alpha-Tocopheryl acetate alpha-Tocopherol E 2020 Donepezil Vitamin E Tocopherols Tocotrienol

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

February 2001

Detailed Description:

OBJECTIVES:

Compare the interval between completion of cancer treatment that included prophylactic cranial irradiation and onset of cognitive decline in patients with small cell lung cancer (SCLC) treated with donepezil and vitamin E vs placebo.
Determine the toxicity of donepezil and vitamin E in these patients.
Determine whether preserved cognitive function favorably impacts quality of life in these patients.
Determine the natural history of cognitive decline in these patients after cancer treatment.
Determine whether genotypes of apolipoprotein E predict decline in cognitive function among patients at risk for treatment-associated dementia and whether these genotypes predict duration of disease-free survival among patients who have achieved complete response after treatment for SCLC.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to cognitive function (normal vs mild to moderate dysfunction vs severe dysfunction) and age (60 and under vs over 60).

Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral donepezil daily and vitamin E twice daily.
Arm II: Patients receive oral placebos according to the same schedule as the study drugs in arm I.

All patients begin treatment within 2 weeks after completion of prophylactic cranial irradiation. Treatment continues for a minimum of 1 month in the absence of disease progression, unacceptable toxicity, or a 3.0 point drop on the Mini Mental State Examination (MMSE) and/or a 5 point drop on the Blessed Dementia Scale.

Cognition is assessed using the Blessed Dementia Scale and the MMSE at baseline and then every 3 months during study.

Quality of life and depression are assessed at baseline and then every 3 months during study.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 104 patients (52 per arm) will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of small cell lung cancer (SCLC)
- Must meet one of the following conditions:
  - Enrolled no more than 4 weeks before initiation of prophylactic cranial irradiation (PCI) OR
  - Enrolled no more than 10 days after initiation of PCI
- Limited or extensive stage SCLC with complete response (CR) outside chest allowed
Must have CR or minimal disease after completion of intended course of chemotherapy
No disease progression since initiation of PCI
No prior or concurrent CNS metastases

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

At least 12 weeks

Hematopoietic:

Not specified

Hepatic:

Bilirubin no greater than 1.5 mg/dL

Renal:

Creatinine no greater than 2 times upper limit of normal

Cardiovascular:

No sick sinus syndrome or other symptomatic supraventricular conduction disorders even if symptoms currently controlled by antiarrhythmics

Pulmonary:

No history of asthma or chronic obstructive pulmonary disease requiring chronic oxygen therapy

Other:

No medical or psychiatric condition that would increase risk
No seizure disorder
No ongoing alcohol abuse

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

See Disease Characteristics
No concurrent anticancer chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

See Disease Characteristics

Surgery:

Not specified

Other:

No concurrent medications that would impair baseline cognitive function or are likely to be dose escalated over the next few months
No other concurrent vitamin E

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006349

Locations

United States, Arizona
CCOP - Scottsdale Oncology Program
Scottsdale, Arizona, United States, 85259-5404
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Illinois
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61602
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1016
Siouxland Hematology-Oncology
Sioux City, Iowa, United States, 51101-1733
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Nebraska
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
United States, North Dakota
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
Medcenter One Health System
Bismarck, North Dakota, United States, 58501
United States, Pennsylvania
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212-4772
United States, South Dakota
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57709

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Aminah Jatoi, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Jatoi A, Kahanic SP, Frytak S, Schaefer P, Foote RL, Sloan J, Petersen RC. Donepezil and vitamin E for preventing cognitive dysfunction in small cell lung cancer patients: preliminary results and suggestions for future study designs. Support Care Cancer. 2005 Jan;13(1):66-9. Epub 2004 Oct 9.

Study ID Numbers:	CDR0000068206, NCCTG-N99C5, NCI-P00-0169
Study First Received:	October 4, 2000
Last Updated:	May 9, 2009
ClinicalTrials.gov Identifier:	NCT00006349 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

limited stage small cell lung cancer
extensive stage small cell lung cancer
recurrent small cell lung cancer
psychosocial effects/treatment

radiation toxicity
quality of life
delirium
depression

Study placed in the following topic categories:

Thoracic Neoplasms
Neurotransmitter Agents
Antioxidants
Carcinoma, Neuroendocrine
Tocopherol
Quality of Life
Cholinergic Agents
Tocopherols
Signs and Symptoms
Respiratory Tract Diseases
Tocotrienol
Lung Neoplasms
Mental Disorders
Vitamins
Neoplasms, Germ Cell and Embryonal

Donepezil
Tocotrienols
Neuroepithelioma
Micronutrients
Dementia
Neurobehavioral Manifestations
Delirium
Nootropic Agents
Tocopherol acetate
Depression
Trace Elements
Confusion
Depressive Disorder
Cognition Disorders
Recurrence

Additional relevant MeSH terms:

Thoracic Neoplasms
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cholinergic Agents
Neoplasms by Site
Lung Neoplasms
Therapeutic Uses
Delirium
Tocopherol acetate
Depression
Nervous System Diseases
Confusion
Depressive Disorder
Behavioral Symptoms

Carcinoma
Alpha-Tocopherol
Carcinoma, Small Cell
Neuroectodermal Tumors
Cholinesterase Inhibitors
Neoplasms
Vitamin E
Delirium, Dementia, Amnestic, Cognitive Disorders
Lung Diseases
Mood Disorders
Neoplasms, Glandular and Epithelial
Antioxidants
Carcinoma, Neuroendocrine
Neoplasms, Nerve Tissue
Tocopherols

ClinicalTrials.gov processed this record on July 02, 2009