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Donepezil in Treating Patients Who Have Undergone Radiation Therapy for Brain Tumors

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences
ClinicalTrials.gov Identifier:
NCT00369785
First received: August 24, 2006
Last updated: May 25, 2017
Last verified: November 2016
  Purpose

RATIONALE: Donepezil may help lessen confusion and fatigue and improve mood and quality of life in patients who have undergone radiation therapy for brain tumors. It is not yet known whether donepezil is more effective than a placebo in lessening side effects of radiation therapy in patients with brain tumors.

PURPOSE: This randomized phase III trial is studying donepezil to see how well it works in lessening side effects of radiation therapy compared with a placebo in patients who have undergone radiation therapy for brain tumors.


Condition Intervention Phase
Brain Tumors Metastatic Disease Drug: donepezil hydrochloride Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Supportive Care
Official Title: Phase III Double Blind, Placebo Controlled Study of Donepezil in the Irradiated Brain

Resource links provided by NLM:


Further study details as provided by Wake Forest University Health Sciences:

Primary Outcome Measures:
  • Memory as Quantified by HVLT-immediate Recall [ Time Frame: 24 weeks ]
    Memory is quantified using the Hopkins Verbal Learning Test (HVLT) - immediate recall. Participants are asked to recall 12 words. Each recalled word is given one point. They are given three trials. The total score is the sum of the recalled words. The range for HVLT-Immediate recall is 0 to 36. Higher scores represent better memory.

  • Memory as Quantified by the HVLT-discrimination [ Time Frame: 24 weeks ]
    In the Hopkins Verbal Learning Test - discrimination, participants are given lists of 12 correct words and 12 incorrect words. HVLT-discrimination is the number of correctly recognized words minus the number incorrectly recognized. The range for this outcome measure is -12 to 12. Higher scores represent better memory.


Enrollment: 198
Study Start Date: January 2008
Study Completion Date: June 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I - Donepezil
Weeks 1-6: One 5 mg tablet orally donepezil hydrochloride Weeks 7-24: Two 5mg tablets per day
Drug: donepezil hydrochloride
Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily
Other Name: Donepezil
Placebo Comparator: Arm II - Control
Weeks 1-6: One placebo tablet per day Weeks 7-24: Two placebo tablets per day
Drug: Placebo
Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day

Detailed Description:

OBJECTIVES:

Primary

  • Compare the effect of donepezil hydrochloride vs placebo, in terms of improving neurocognitive symptom cluster (i.e., cognitive impairment, subjective confusion, and fatigue), in patients who have undergone partial- or whole-brain irradiation for brain tumors.

Secondary

  • Compare the effect of these regimens on mood and quality of life in these patients.

OUTLINE: This is a prospective, double-blind, placebo-controlled, randomized, multicenter study. Patients are stratified according to prior brain irradiation type (whole-brain vs partial-brain) and study site. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral donepezil hydrochloride once or twice daily for up to 24 weeks in the absence of unacceptable toxicity.
  • Arm II: Patients receive oral placebo once or twice daily for up to 24 weeks in the absence of unacceptable toxicity.

Patients complete self-reported questionnaires (quality of life, fatigue, subjective confusion, neurocognitive battery, and mood) at baseline and 12 and 24 weeks.

PROJECTED ACCRUAL: A total of 200 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Adults >18 years old.
  • Life expectancy of at least > 30 weeks.
  • Must have received a prior course of at least 30 Gy fractionated whole or partial brain irradiation for treatment of a primary brain tumor or metastatic disease to the brain.
  • Must have completed radiation > 6 months prior to enrollment and have no radiographic evidence of brain disease, or stable brain disease defined as no evidence of tumor progression in the 3 months prior to enrollment.
  • Patients who have undergone one or more treatments with single fraction stereotactic radiosurgery (SRS) in addition to whole or partial brain irradiation are eligible, as long as the SRS was completed > 6 months prior to registration if NED or stable disease.
  • Radiation treatment records must be available for all prior radiation treatments (external beam and/or SRS).
  • Patients who have received PCI (prophylactic cranial irradiation) are eligible.
  • Karnofsky Performance Status must be > 60 or ECOG 0-2.
  • Treatment with steroids, anti-cholinergics, anti-epileptics, anti-depressants, and /or sedatives/benzodiazepines is acceptable, but the patient must be on a stable or decreasing dose at the time of study entry.
  • Patients using narcotic analgesics on a stable dose and/or prn basis are eligible.
  • Patients currently on a stable dose of Methylphenidate or Dextramphetamine are eligible.
  • For patients with brain metastases, if extracranial primary or metastatic disease is present, it must have responded to local and/or systemic treatment. Must be stable in the 3 months prior to enrollment.
  • Must not be receiving chemotherapy at the time of enrollment.
  • Patient must not have any planned therapy, including surgery, brain radiation of any type, chemotherapy, or immunotherapy during the next 30 weeks for brain or extracranial primary metastatic disease.
  • Hormonal therapy for patients with breast or prostate cancer is acceptable.
  • Breast patients receiving therapy with Herceptin are allowed.
  • Patients must be able to give informed consent to participate in the study, including signing the consent form.
  • Patients must have a telephone.

EXCLUSION CRITERIA:

  • Patients cannot be currently taking dementia drugs, cognitive enhancers, neuroleptics, and/or anti-parkinsonian agents. For patients who have used these drugs in the past, they must not have used them in the 2 weeks prior to enrolling on the study.
  • Hypersensitivity to donepezil.
  • Patients may not currently be taking Ketoconazole or Quindine
  • Arrythmias including bradycardia or heartblock
  • Patients who have received, GliaSite or other type of brain brachytherapy, (Gliadel Wafers permitted) convection enhanced delivery of immunotoxins, and/or any other investigational modalities for treatment of their brain tumor. The effects of donepezil on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • It is unknown whether donepezil is excreted in breast milk, for this reason women who are currently breast-feeding are not eligible for this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00369785

Locations
United States, Kansas
Associates in Womens Health, PA - North Review
Wichita, Kansas, United States, 67208
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, United States, 67208
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, United States, 67214
CCOP - Wichita
Wichita, Kansas, United States, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
United States, Maine
Central Maine Comprehensive Cancer Center at Central Maine Medical Center
Lewiston, Maine, United States, 04240
United States, New Hampshire
New Hampshire Oncology - Hematology, PA - Hooksett
Hooksett, New Hampshire, United States, 03106
Lakes Region General Hospital
Laconia, New Hampshire, United States, 03246
United States, New York
Don Monti Comprehensive Cancer Center at North Shore University Hospital
Manhasset, New York, United States, 11030
United States, North Dakota
CCOP - MeritCare Hospital
Fargo, North Dakota, United States, 58122
Trinity CancerCare Center
Minot, North Dakota, United States, 58701
United States, Ohio
Summa Center for Cancer Care at Akron City Hospital
Akron, Ohio, United States, 44309-2090
MetroHealth Cancer Care Center at MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
United States Air Force Medical Center - Wright-Patterson
Wright-Patterson Air Force Base, Ohio, United States, 45433-5529
United States, Tennessee
Thompson Cancer Survival Center
Knoxville, Tennessee, United States, 37916
United States, Wisconsin
Gundersen Lutheran Center for Cancer and Blood
La Crosse, Wisconsin, United States, 54601
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Investigators
Principal Investigator: Stephen Rapp, PhD Wake Forest University Health Sciences
  More Information

Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT00369785     History of Changes
Other Study ID Numbers: REBACCCWFU 91105
U10CA081851 ( US NIH Grant/Contract Award Number )
Study First Received: August 24, 2006
Results First Received: July 15, 2015
Last Updated: May 25, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Wake Forest University Health Sciences:
cognitive/functional effects
fatigue
psychosocial effects of cancer and its treatment
radiation toxicity
tumors metastatic to brain
adult brain stem glioma
adult central nervous system germ cell tumor
adult choroid plexus tumor
adult craniopharyngioma
adult mixed glioma
adult anaplastic meningioma
meningeal melanocytoma
adult meningeal hemangiopericytoma
adult grade I meningioma
adult grade II meningioma
adult grade III meningioma
adult papillary meningioma
adult anaplastic oligodendroglioma
adult oligodendroglioma
adult pineoblastoma
adult pineocytoma
adult anaplastic astrocytoma
adult diffuse astrocytoma
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
adult pilocytic astrocytoma
adult ependymoblastoma
adult medulloblastoma
adult supratentorial primitive neuroectodermal tumor (PNET)

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasm Metastasis
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplastic Processes
Pathologic Processes
Donepezil
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents

ClinicalTrials.gov processed this record on June 23, 2017