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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

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

Treatments: Dietary Supplement: vitamin E; Other: placebo; Drug: donepezil hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00006349

NCI-P00-0169

NCCTG-N99C5

CDR0000068206 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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9 participants in 2 patient groups, including a placebo group

donepezil + vitamin E

Experimental group

Description:

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.

Treatment:

Drug: donepezil hydrochloride

Dietary Supplement: vitamin E

placebo

Placebo Comparator group

Description:

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.

Treatment:

Other: placebo