Donepezil in Treating Patients Who Have Undergone Radiation Therapy for Brain Tumors
Condition: Brain Tumors; Metastatic Disease
MeSH terms: Brain Neoplasms; Neoplasm Metastasis
Intervention: donepezil hydrochloride; Placebo
Intervention description: Weeks 1-6: One tablet Donepezil 5 mg given daily Weeks 7-24: Two Donepezil 5 mg tablets given daily; Weeks 1-6: One tablet per day Weeks 7-24: Two tablets per day
Intervention MeSH terms: Donepezil
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 198.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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.
    

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.