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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Cognitive/Functional Effects, Delirium, Depression, Lung Cancer, Radiation Toxicity

Intervention / Treatment
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* Dietary Supplement: vitamin E
* Drug: donepezil hydrochloride
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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 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: Chemotherapy: See Disease Characteristics No concurrent anticancer chemotherapy 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

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: donepezil + vitamin E<br>Patients receive oral donepezil daily and vitamin E twice daily. 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. | Dietary Supplement: vitamin E<br> <br> Drug: donepezil hydrochloride<br> <br> |
| Placebo Comparator: placebo<br>Patients receive oral placebo twice daily. 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. | Other: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life |  | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression, delirium, cognitive/functional effects, radiation toxicity, limited stage small cell lung cancer, extensive stage small cell lung cancer, recurrent small cell lung cancer