One of the drugs for the study is not commercially available.

The main purpose of this study is to find out the highest possible dose of maprotiline that can be given safely in combination with temozolomide and tamoxifen.

The main purpose of this study is to find out the highest possible dose of maprotiline that can be given safely in combination with temozolomide and tamoxifen. Temozolomide is approved to treat glioblastoma and the investigator wants to understand what doses are safe to use. Tamoxifen has been used for many years to treat breast cancer and there have also been studies combining it with temozolomide for the treatment of brain tumors that have shown the combination to be safe. In this study, the investigator will be adding maprotiline to temozolomide and tamoxifen, determining the highest possible dose that is safe, making sure there are no significant drug interactions and studying the safety of this combination.

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 undergone upfront therapy that included a combination of radiotherapy and concurrent and adjuvant temozolomide.
• Patients must have shown unequivocal radiographic evidence for tumor progression by 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 five days. If the steroid dose is increased between the date of imaging and registration a new baseline MRI is required.
• Patients must have tissue confirmation of histology at the University of Rochester
• 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 PET or Thallium scanning, MR spectroscopy, MR 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.
• Patients who have undergone re-resection for recurrent disease are eligible but must have an interval of 7 days prior to starting therapy.
• 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 > 18 years old, and with a life expectancy > eight weeks.
• Karnofsky Performance Status ≥ 70
• Patients must have an interval of at least 28 days from any investigational agent or from prior cytotoxic therapy, six weeks from prior nitrosureas, three weeks from procarbazine and two weeks from vincristine.
• Patients must have failed prior radiotherapy and must have an interval of greater than 90 days from completion of initial radiation therapy to study entry.
• WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 8 gm/dl). Patients must have adequate liver function (SGOT and bilirubin < 1.5 times ULN), and adequate renal function (creatinine clearance >30ml/min as measured by Cockroft-Gault formula) \