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)
18 Years
N/A
Both
Cognitive/Functional Effects, Delirium, Depression, Lung Cancer, Radiation Toxicity
Trial Information
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)
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care
Principal Investigator
Aminah Jatoi, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Federal Government
Study ID:
CDR0000068206
NCT ID:
NCT00006349
Start Date:
February 2001
Completion Date:
Related Keywords:
- Cognitive/Functional Effects
- Delirium
- Depression
- Lung Cancer
- Radiation Toxicity
- depression
- delirium
- cognitive/functional effects
- radiation toxicity
- limited stage small cell lung cancer
- extensive stage small cell lung cancer
- recurrent small cell lung cancer
- Delirium
- Depression
- Depressive Disorder
- Lung Neoplasms
- Small Cell Lung Carcinoma
- Radiation Injuries
Name | Location |
|---|---|
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| CCOP - Wichita | Wichita, Kansas 67214-3882 |
| CCOP - Missouri Valley Cancer Consortium | Omaha, Nebraska 68131 |
| CCOP - Illinois Oncology Research Association | Peoria, Illinois 61602 |
| CCOP - Carle Cancer Center | Urbana, Illinois 61801 |
| CCOP - Iowa Oncology Research Association | Des Moines, Iowa 50309-1016 |
| CCOP - Scottsdale Oncology Program | Scottsdale, Arizona 85259-5404 |
| CCOP - Cedar Rapids Oncology Project | Cedar Rapids, Iowa 52403-1206 |
| Siouxland Hematology-Oncology | Sioux City, Iowa 51101-1733 |
| CCOP - Merit Care Hospital | Fargo, North Dakota 58122 |
| Rapid City Regional Hospital | Rapid City, South Dakota 57709 |
| CCOP - Sioux Community Cancer Consortium | Sioux Falls, South Dakota 57105-1080 |
| Allegheny General Hospital | Pittsburgh, Pennsylvania 15212-4772 |
| Mayo Clinic | Jacksonville, Florida 32224 |
| Medcenter One Health System | Bismarck, North Dakota 58501 |
