Clinical trial NCT00369785: Donepezil in Treating Patients Who Have Undergone Radiation Therapy for Brain Tumors
Official title: Phase III Double Blind, Placebo Controlled Study of Donepezil in the Irradiated Brain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain Tumors
Metastatic Disease
Keywords: 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)
adult anaplastic ependymoma
adult ependymoma
adult myxopapillary ependymoma
adult subependymoma
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-08-29
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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 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.

Primary outcomes:
measure: Memory as Quantified by HVLT-immediate Recall
timeFrame: 24 weeks
measure: Memory as Quantified by the HVLT-discrimination
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Lewiston
country: United States
facility: Central Maine Comprehensive Cancer Center at Central Maine Medical Center
state: Maine
city: Hooksett
country: United States
facility: New Hampshire Oncology - Hematology, PA - Hooksett
state: New Hampshire
city: Laconia
country: United States
facility: Lakes Region General Hospital
state: New Hampshire
city: Manhasset
country: United States
facility: Don Monti Comprehensive Cancer Center at North Shore University Hospital
state: New York
city: Fargo
country: United States
facility: CCOP - MeritCare Hospital
state: North Dakota
city: Minot
country: United States
facility: Trinity CancerCare Center
state: North Dakota
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Wright-Patterson Air Force Base
country: United States
facility: United States Air Force Medical Center - Wright-Patterson
state: Ohio
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
city: La Crosse
country: United States
facility: Gundersen Lutheran Center for Cancer and Blood
state: Wisconsin
Study officials:
affiliation: Wake Forest University Health Sciences
name: Stephen Rapp, PhD
role: PRINCIPAL_INVESTIGATOR
References: