Clinical trial NCT00006349: Donepezil and Vitamin E to Prevent Side Effects Caused By Radiation Therapy to the Head in Patients Receiving Treatment for Small Cell Lung Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cognitive/Functional Effects
Delirium
Depression
Lung Cancer
Radiation Toxicity
Keywords: depression
delirium
cognitive/functional effects
radiation toxicity
limited stage small cell lung cancer
extensive stage small cell lung cancer
recurrent small cell lung cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-05-29
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility 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

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

Primary outcomes:
measure: 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
timeFrame: Up to 6 months
Secondary outcomes:
measure: Quality of life
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Scottsdale Oncology Program
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Bismarck
country: United States
facility: Medcenter One Health System
state: North Dakota
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
Study officials:
affiliation: Mayo Clinic
name: Aminah Jatoi, MD
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1007/s00520-004-0696-0. Epub 2004 Oct 9.