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

NCT ID: NCT00006349

Last Updated: 2016-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-02-28
• Study Completion Date: 2007-01-31

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.

Conditions

Cognitive/Functional Effects; Delirium; Depression; Lung Cancer; Radiation Toxicity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

vitamin E

Intervention Type: DIETARY_SUPPLEMENT

donepezil hydrochloride

Intervention Type: DRUG

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Interventions

vitamin E

Intervention Type: DIETARY_SUPPLEMENT

donepezil hydrochloride

Intervention Type: DRUG

placebo

Intervention Type: OTHER

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aminah Jatoi, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

CCOP - Scottsdale Oncology Program

Scottsdale, Arizona, United States

Mayo Clinic

Jacksonville, Florida, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Siouxland Hematology-Oncology

Sioux City, Iowa, United States

CCOP - Wichita

Wichita, Kansas, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Medcenter One Health System

Bismarck, North Dakota, United States

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 15480814 (View on PubMed)

Other Identifiers

CDR0000068206

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-P00-0169

Identifier Type: -

Identifier Source: secondary_id

NCCTG-N99C5

Identifier Type: -

Identifier Source: org_study_id