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

Phase 3

Completed

• Conditions: Cognitive/Functional Effects; Delirium; Depression; Lung Cancer; Radiation Toxicity
• Interventions: Dietary Supplement: vitamin E; Other: placebo; Drug: donepezil hydrochloride

• Registration Number: NCT00006349
• Lead Sponsor: Alliance for Clinical Trials in Oncology

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.

Study Timeline

• Study First Submitted: 2000-10-04
• Study Start: 2001-02
• Study First Submitted QC: 2003-05-28
• Study First Posted: 2003-05-29
• Primary Completion: 2005-01
• Study Completion: 2007-01
• Status Verified: 2016-07
• Last Update Submitted: 2016-07-12
• Last Update Posted: 2016-07-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
donepezil + vitamin E	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.
donepezil + vitamin E	donepezil hydrochloride	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.
placebo	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.

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method
Quality of life	Up to 6 months

Trial Locations

Locations (15)

Medcenter One Health System; 🇺🇸 Bismarck, North Dakota, United States

CCOP - Iowa Oncology Research Association; 🇺🇸 Des Moines, Iowa, United States

Mayo Clinic Cancer Center; 🇺🇸 Rochester, Minnesota, United States

Siouxland Hematology-Oncology; 🇺🇸 Sioux City, Iowa, United States

Allegheny General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

CCOP - Cedar Rapids Oncology Project; 🇺🇸 Cedar Rapids, Iowa, United States

CCOP - Missouri Valley Cancer Consortium; 🇺🇸 Omaha, Nebraska, United States

CCOP - Wichita; 🇺🇸 Wichita, Kansas, United States

Mayo Clinic; 🇺🇸 Jacksonville, Florida, United States

CCOP - Carle Cancer Center; 🇺🇸 Urbana, Illinois, United States

CCOP - Scottsdale Oncology Program; 🇺🇸 Scottsdale, Arizona, United States

CCOP - Illinois Oncology Research Association; 🇺🇸 Peoria, Illinois, United States

CCOP - Merit Care Hospital; 🇺🇸 Fargo, North Dakota, United States

CCOP - Sioux Community Cancer Consortium; 🇺🇸 Sioux Falls, South Dakota, United States

Rapid City Regional Hospital; 🇺🇸 Rapid City, South Dakota, United States