Brain TumorsPhase 3NCT00369785
Donepezil in Treating Patients Who Have Undergone Radiation Therapy for Brain Tumors
A Phase 3 study testing donepezil hydrochloride in people with Brain Tumors and Metastatic Disease, run by Wake Forest University Health Sciences at 16 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Tumors, Metastatic Disease
- What is being tested?
- donepezil hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 198 participants
- Where
- 16 sitesUnited States
- Study dates
- Feb 2008to 1 Jul 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 18Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Summa Center for Cancer Care at Akron City Hospital
Akron, Ohio, 44309-2090
MetroHealth Cancer Care Center at MetroHealth Medical Center
Cleveland, Ohio, 44109
CCOP - MeritCare Hospital
Fargo, North Dakota, 58122
New Hampshire Oncology - Hematology, PA - Hooksett
Hooksett, New Hampshire, 03106
Thompson Cancer Survival Center
Knoxville, Tennessee, 37916
Gundersen Lutheran Center for Cancer and Blood
La Crosse, Wisconsin, 54601
Lakes Region General Hospital
Laconia, New Hampshire, 03246
Central Maine Comprehensive Cancer Center at Central Maine Medical Center
Lewiston, Maine, 04240
Don Monti Comprehensive Cancer Center at North Shore University Hospital
Manhasset, New York, 11030
Trinity CancerCare Center
Minot, North Dakota, 58701
Associates in Womens Health, PA - North Review
Wichita, Kansas, 67208
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, 67208
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, 67214
CCOP - Wichita
Wichita, Kansas, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, 67214
United States Air Force Medical Center - Wright-Patterson
Wright-Patterson Air Force Base, Ohio, 45433-5529
About this study
Official title: Phase III Double Blind, Placebo Controlled Study of Donepezil in the Irradiated Brain
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.
Read the 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.
- Conditions
- Brain Tumors, Metastatic Disease
- Being tested
- donepezil hydrochloride, Placebo
- 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
- Medical subject headings
- Brain Neoplasms, Neoplasm Metastasis, Fatigue, Radiation Injuries, Choroid Plexus Neoplasms, Craniopharyngioma, Glioma, Meningioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
donepezil hydrochlorideDrug
Also called Donepezil
Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily
PlaceboDrug
Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day
| Study group | Role | What they receive |
|---|---|---|
| Arm I - Donepezil | Experimental | Weeks 1-6: One 5 mg tablet orally donepezil hydrochloride Weeks 7-24: Two 5mg tablets per day Receives: Drug: donepezil hydrochloride |
| Arm II - Control | Placebo comparator | Weeks 1-6: One placebo tablet per day Weeks 7-24: Two placebo tablets per day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Memory as Quantified by HVLT-immediate Recall
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.
Measured: 24 weeks
Memory as Quantified by the HVLT-discrimination
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.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2006 (estimated)
- Study startFeb 2008
- Primary completion1 Jul 2012
- Study completion1 Jul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Brain TumorsStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 198 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Stephen Rapp, PhD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00369785
- Sponsor's protocol ID
- IRB00000551
- Other IDs
- U10CA081851, REBACCCWFU 91105
- Status last verified
- Sep 2021
- First submitted
- 24 Aug 2006
- Last updated
- 20 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Double Blind, Placebo Controlled Study of Donepezil in the Irradiated Brain
- ClinicalTrials.gov ID
- NCT00369785
- Acronym / sponsor ID
- IRB00000551
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 198 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2008 (actual)
- Primary completion
- 1 Jul 2012 (actual)
- Study completion
- 1 Jul 2012 (actual)
- First posted
- 29 Aug 2006 (estimated)
- Results
- Posted 9 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I - Donepezil | Experimental | Drug: donepezil hydrochlorideWeeks 1-6: One 5 mg tablet orally donepezil hydrochloride Weeks 7-24: Two 5mg tablets per day |
| Arm II - Control | Placebo comparator | Drug: PlaceboWeeks 1-6: One placebo tablet per day Weeks 7-24: Two placebo tablets per day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| donepezil hydrochlorideAlso: DonepezilWeeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily | Drug | Arm I - Donepezil |
| PlaceboWeeks 1-6: One tablet per day Weeks 7-24: Two tablets per day | Drug | Arm II - Control |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Data Available: Select individual patient-level data form this trial can be requested from the NCTN/NCORP Data ArchiveLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Rapp, PhD principal investigator
Wake Forest University Health Sciences
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing donepezil hydrochloride in people with Brain Tumors and Metastatic Disease, run by Wake Forest University Health Sciences at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Memory as Quantified by HVLT-immediate Recall (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2021.