Memantine for Recurrent Glioblastoma
Condition: Glioblastoma
MeSH terms: Glioblastoma
Intervention: memantine
Intervention description: 10 milligrams orally twice a day
Intervention MeSH terms: Memantine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent

Summary:

      The purpose of this study is to determine if a medication called memantine is effective in
      treating glioblastoma. Memantine targets a specific receptor, called a glutamate receptor,
      which is thought to be involved in the growth of brain tumors. It has previously been studied
      for other types of conditions, such as Alzheimer's disease, but it has not yet been evaluated
      in the treatment of brain tumors. The investigators will also be determining how common it is
      for patients with brain tumors to have side effects to memantine. Memantine will be taken by
      mouth twice a day.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with histologically proven World Health Organization (WHO) grade IV gliomas.
             Patients will be eligible if the original histology was a grade II or grade III glioma
             as long as a subsequent histological diagnosis of a grade IV glioma is confirmed.

          -  Patients must have shown unequivocal radiographic evidence for tumor progression by
             magnetic resonance imaging (MRI) scan. A scan should be performed within 10 days prior
             to registration and on a steroid dose that has been stable for at least 5 days. If the
             steroid dose is increased between the date of imaging and registration a new baseline
             MRI is required.

          -  Patients with prior therapy that included interstitial brachytherapy or stereotactic
             radiosurgery (including gamma-knife or cyber-knife) must have confirmation of true
             progressive disease rather than radiation necrosis based upon either positron emission
             tomography (PET) or Thallium scanning, magnetic resonance spectroscopy (MRS), magnetic
             resonance perfusion, or surgical documentation of disease. The decision of which
             modality to use to make this confirmation will be at the discretion of the
             investigator.

          -  All patients must sign an informed consent indicating that they are aware of the
             investigational nature of this study. Patients must have signed an authorization for
             the release of their protected health information.

          -  Age greater than 18 years old, and with a life expectancy greater than 8 weeks.

          -  Karnofsky Performance Status greater or equal to 60

          -  Patients must have an interval of at least 28 days from any investigational agent or
             from prior cytotoxic therapy, 6 weeks from prior nitrosureas, 3 weeks from
             procarbazine and 2 weeks from vincristine.

          -  Patients must have failed prior radiotherapy and must have an interval of greater than
             42 days from completion of initial radiation therapy to study entry or 28 days since
             radiation therapy used for recurrent tumor.

          -  Since memantine is not associated with myelosuppression, patients with persistent
             effects on bone marrow function from prior cytotoxic chemotherapies will be eligible
             as long as: white blood cells > 1,000/µl, absolute neutrophil count > 500/mm3,
             platelet count of > 50,000/mm3, and hemoglobin > 8 gm/dl). Patients must have adequate
             liver function and adequate renal function before starting therapy. These tests must
             be performed within 2 weeks prior to treatment initiation. Eligibility level for
             hemoglobin may be reached by transfusion.

          -  Patients must have a calculated creatinine clearance > 30 milliliters/minute.

        Exclusion Criteria:

          -  Patients who are within 3 months of treatment with radiation and concurrent
             temozolomide will not be eligible unless there are new enhancing abnormalities outside
             the high dose radiation fields (i.e beyond the 80% isodose line) or surgical
             demonstration of active tumor.

          -  Patients must not be pregnant and must agree to practice adequate contraception. Women
             of childbearing potential must have a negative pregnancy test documented within 7 days
             prior to registration. Women must not be breastfeeding.

          -  Patients with a history of other cancer (except non-melanoma skin cancer or cancer of
             the cervix), unless in complete remission for at least 3 years are ineligible.

          -  Patients must not have any significant medical illnesses or other history that in the
             investigator's opinion cannot be adequately controlled with appropriate therapy or
             would compromise the patient's ability to tolerate this therapy.

          -  Patients must not have any disease that will obscure toxicity or dangerously alter
             drug metabolism.

          -  Patients must not have prior or concurrent use of memantine or treatment with other
             N-methyl D-asparate (NMDA) receptor blocking therapies.

          -  Active drug or alcohol use or dependence that, in the opinion of the investigator,
             would interfere with adherence to study requirements.

          -  Inability or unwillingness of subject or legal guardian/representative to give written
             informed consent.