Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Supportive care	Completed	18 and over	NCI	NCCTG-N99C5 NCI-P00-0169, NCT00006349

Objectives

1. 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.
2. Determine the toxicity of donepezil and vitamin E in these patients.
3. Determine whether preserved cognitive function favorably impacts quality of life in these patients.
4. Determine the natural history of cognitive decline in these patients after cancer treatment.
5. 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.

Entry 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

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

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

Expected Enrollment

A total of 104 patients (52 per arm) will be accrued for this study within 3 years.

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.

Jatoi A, Kahanic SP, Frytak S, et al.: 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 13 (1): 66-9, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Aminah Jatoi, MD, Protocol chair		Ph: 507-284-4918

Registry Information
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)
Trial Start Date		2001-02-06
Registered in ClinicalTrials.gov		NCT00006349
Date Submitted to PDQ		2000-08-04
Information Last Verified		2002-12-03
NCI Grant/Contract Number		CA31946

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