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)”

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.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Placebo Control

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.

Intervention(s) in this Clinical Trial

• Dietary Supplement: vitamin E
• Drug: donepezil hydrochloride
• Procedure: quality-of-life assessment

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: North Central Cancer Treatment Group

Overall Clinical Trial Officials and Contacts

Aminah Jatoi, MD Study Chair Mayo Clinic  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00006349

Study ID Number: CDR0000068206

ClinicalTrials.gov Identifier: NCT00006349

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database