Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
About this trial
This is an interventional treatment trial for Adult Giant Cell Glioblastoma
Eligibility Criteria
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 < 1.5 mg/dL Prothrombin time (PT)/ international normalized ratio (INR) ≤ 1.5 (INR < 3.0 for patients on anticoagulation therapy) INR < 1.1 times upper limit of normal (ULN) (for patients on prophylactic anticoagulation therapy [low-dose warfarin]) Fasting cholesterol < 350 mg/dL (for patients receiving temsirolimus and sorafenib) Fasting triglycerides < 400 mg/dL (for patients receiving temsirolimus and sorafenib) Well-controlled hypertension (e.g., systolic blood pressure ≤ 140 mm Hg or diastolic pressure ≤ 90 mm Hg) allowed Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for at least 2 weeks (women) or 3 months (men) after completion of study treatment No peripheral neuropathy > 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) No concurrent enzyme-inducing antiepileptic drugs (e.g., carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital, or primidone) Dexamethasone allowed No concurrent hepatic cytochrome p450 enzyme-inducing anticonvulsants No other concurrent investigational agents or anticancer therapies, including chemotherapy, radiotherapy, hormonal therapy, or immunotherapy No concurrent prophylactic filgrastim (G-CSF) or other hematopoietic colony-stimulating factors Full-dose anticoagulants allowed provided both of the following criteria are met: In-range INR (between 2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
Sites / Locations
- University of California at Los Angeles
- University of California San Francisco
- Dana-Farber Cancer Institute
- Memorial Sloan-Kettering Cancer Center
- University of Pittsburgh
- M D Anderson Cancer Center
- University of Wisconsin Hospital and Clinics
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Group 1
Group 2
Group 3
Patients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28.
Patients receive sorafenib tosylate as in group 1. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
Patients receive sorafenib tosylate as in group 1. Patients also receive oral tipifarnib twice daily on days 1-21.