Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma

Inclusion Criteria

• Histologically confirmed intracranial glioblastoma multiforme or gliosarcoma
• Evidence of tumor progression by MRI or CT scan within the past 14 days AND on a steroid dose that has been stable for ≥ 5 days
• Patients who underwent prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis by either positron emission tomography or thallium scanning, magnetic resonance (MR) spectroscopy, or surgical documentation of disease
• Recent resection of recurrent or progressive tumor allowed
• Residual disease is not required
• Treatment for any number of prior relapses, defined as disease progression after initial therapy (i.e., radiotherapy with or without chemotherapy if used as initial treatment), allowed (phase I)
• No more than 3 prior therapies (initial therapy and therapy for 2 relapses) (phase II)
• Each of the following is considered 1 relapse:
• Disease progression after initial therapy (i.e., radiotherapy with or without chemotherapy if used as initial therapy)
• Underwent a surgical resection for relapsed disease and received no anticancer therapy for up to 12 weeks after surgical resection AND then underwent a subsequent surgical resection
• Received prior therapy for a low-grade glioma, followed by a surgical diagnosis of glioblastoma
• Failed prior radiotherapy
• 15 unstained paraffin slides or 1 tissue block must be available from original surgery, definitive surgery, or surgery closest to the initiation of this study (phase II)
• Karnofsky performance status 60-100%
• White Blood Cell (WBC) ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL (transfusion allowed)
• Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN)
• Total bilirubin normal
• Creatinine grade 1 (for patients receiving sorafenib and tipifarnib)
• No evidence of bleeding diathesis or coagulopathy
• No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for ≥ 3 years
• No significant traumatic injury within the past 21 days
• No active infection or serious medical illness that would preclude study treatment
• No condition that would impair ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation or active peptic ulcer disease)
• No HIV disease
• No allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole or econazole) or a history of allergic reactions attributed to any compound of similar chemical or biological composition to tipifarnib (for patients receiving sorafenib and tipifarnib)
• No other disease that would obscure toxicity or dangerously alter drug metabolism
• Recovered from prior therapy
• At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin) (radiosensitizer does not count)
• At least 14 days since prior vincristine
• At least 21 days since prior procarbazine or major surgery
• At least 28 days since prior investigational agent or cytotoxic therapy
• At least 42 days since prior nitrosoureas or radiotherapy
• No prior sorafenib, AEE788, or vatalanib
• No prior surgical procedures affecting absorption
• No prior tipifarnib, lonafarnib, or other agents targeting farnesyl transferase (for patients receiving sorafenib and tipifarnib)
• No prior temsirolimus or mechanistic target of rapamycin (mTOR-targeting agent) (phase II), rapamycin or everolimus, or Akt-pathway inhibitors (for patients receiving sorafenib and temsirolimus)
• No prior erlotinib hydrochloride, multitargeted human epidermal receptor (AEE788), or other epidermal growth factor receptor targeting agents (phase II) (for patients receiving sorafenib and erlotinib hydrochloride)
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