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

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00006349

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Cognitive/Functional Effects Delirium Depression Lung Cancer Radiation Toxicity	Dietary Supplement: vitamin E Drug: donepezil hydrochloride Other: placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Supportive Care

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)

Study Start Date :

Feb 1, 2001

Actual Primary Completion Date :

Jan 1, 2005

Actual Study Completion Date :

Jan 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: donepezil + vitamin E 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 Drug: donepezil hydrochloride
Placebo Comparator: placebo 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

Arm

Intervention/Treatment

Experimental: donepezil + vitamin E

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

Drug: donepezil hydrochloride

Placebo Comparator: placebo

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

Outcome Measures

Primary Outcome Measures

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

Quality of life [Up to 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCOP - Scottsdale Oncology Program	Scottsdale	Arizona	United States	85259-5404
2	Mayo Clinic	Jacksonville	Florida	United States	32224
3	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61602
4	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
5	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa	United States	52403-1206
6	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309-1016
7	Siouxland Hematology-Oncology	Sioux City	Iowa	United States	51101-1733
8	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
9	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
10	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
11	Medcenter One Health System	Bismarck	North Dakota	United States	58501
12	CCOP - Merit Care Hospital	Fargo	North Dakota	United States	58122
13	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212-4772
14	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57709
15	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota	United States	57104