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

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)

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.

Study Overview

• Status: Completed
• Conditions: Depression; Delirium; Lung Cancer; Radiation Toxicity; Cognitive/Functional Effects
• Intervention / Treatment: Other: placebo; Dietary supplement: vitamin E; Drug: donepezil hydrochloride

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5404
      • CCOP - Scottsdale Oncology Program
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Peoria, Illinois, United States, 61602
      • CCOP - Illinois Oncology Research Association
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403-1206
      • CCOP - Cedar Rapids Oncology Project
    • Des Moines, Iowa, United States, 50309-1016
      • CCOP - Iowa Oncology Research Association
    • Sioux City, Iowa, United States, 51101-1733
      • Siouxland Hematology-Oncology
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Medcenter One Health System
    • Fargo, North Dakota, United States, 58122
      • CCOP - Merit Care Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212-4772
      • Allegheny General Hospital
  • South Dakota
    • Rapid City, South Dakota, United States, 57709
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57104
      • CCOP - Sioux Community Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Dietary supplement: vitamin E; Drug: donepezil hydrochloride
Placebo Comparator: 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.	Other: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Quality of life	Up to 6 months

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2001
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: October 4, 2000
• First Submitted That Met QC Criteria: May 28, 2003
• First Posted (Estimate): May 29, 2003

Study Record Updates

• Last Update Posted (Estimate): July 13, 2016
• Last Update Submitted That Met QC Criteria: July 12, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: extensive stage small cell lung cancer; recurrent small cell lung cancer; delirium; depression; limited stage small cell lung cancer; radiation toxicity; cognitive/functional effects
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Depression; Delirium; Lung Neoplasms; Small Cell Lung Carcinoma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Protective Agents; Micronutrients; Vitamins; Antioxidants; Nootropic Agents; Cholinesterase Inhibitors; Vitamin E; Donepezil
• Other Study ID Numbers: NCCTG-N99C5; CDR0000068206 (Registry Identifier: PDQ (Physician Data Query)); NCI-P00-0169