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

Depression Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006349
• Other study ID #: NCCTG-N99C5
• Secondary ID: CDR0000068206NCI
• Status: Completed
• Phase: Phase 3
• First received: October 4, 2000
• Last updated: July 12, 2016
• Start date: February 2001
• Est. completion date: January 2007

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: January 2007
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Cognitive/Functional Effects
• Delirium
• Depression
• Lung Cancer
• Lung Neoplasms
• Radiation Injuries
• Radiation Toxicity
• Small Cell Lung Carcinoma

Intervention

Dietary Supplement:
• vitamin E

Drug:
• donepezil hydrochloride

Other:
• placebo

Locations

Country	Name	City	State
United States	Medcenter One Health System	Bismarck	North Dakota
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	Mayo Clinic	Jacksonville	Florida
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	CCOP - Scottsdale Oncology Program	Scottsdale	Arizona
United States	Siouxland Hematology-Oncology	Sioux City	Iowa
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	CCOP - Wichita	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Quality of life		Up to 6 months	No