| Inclusion Criteria: | 1) Patients with histologically proven intracranial glioblastoma (GBM) or gliosarcoma (GS). Patients will be eligible if the original histology was low-Grade glioma and a subsequent histological diagnosis of a GBM or GS is made.
2) 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. Patients must be registered in the Adult Brain Tumor Consortium(ABTC) database prior to treatment with study drug.
3) Patients must be equal or greater than 18 years old.
4) Patients must have a Karnofsky performance status of equal or greater than 60.
5) Patients with well-controlled hypertension are eligible (systolic blood pressure of equal or less than 140 mgHg or diastolic pressure equal or less than 90 mgHg).
6) Patients must have recovered from the toxic effects of prior therapy: 28 days from any investigational agent, 28 days from prior cytotoxic therapy, 14 days from vincristine, 42 days from nitrosoureas, 21 days from procarbazine administration, and 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.
7) Patients must have adequate bone marrow function (WBC =/> 3,000/mcL, ANC =/> 1,500/mm^3, platelet count of =/> 100,000/mm^3, and hemoglobin =/> 10 gm/dl), Total bilirubin: within normal institutional limits (AST (SGOT)/ALT (SGPT)) </= 2.5 X institutional upper limit of normal (ULN), adequate renal function (creatinine < 1.5 mg/dL), an INR value of < 3.0 (for those patients on anti-coagulation therapy) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
8) Drug specific eligibility criteria for patients enrolling onto arm with CCI-779 (temsirolimus) and Bay 43-9006 (sorafenib) only : fasting cholesterol < 350 mg/dL (9.0 mmol/L) and fasting triglycerides < 400 mg/dL (4.56 mmol/L).
9) Patient does not have any evidence of bleeding diathesis or coagulopathy.
10) Patients on prophylactic anticoagulation therapy (low-dose warfarin): INR level < 1.1 x institutional ULN.
11) Patients on full-dose anticoagulants (e.g., warfarin) are eligible provided that both of the following criteria are met: 1) Patient has an in-range INR (usually between 2-3) on a stable dose or oral anticoagulant or on a stable dose of low molecular weight heparin. 2) Patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
12) Patients must have shown unequivocal radiographic evidence for tumor progression by MRI or CT scan. A scan should be performed within 14 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 MR/CT is required. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
13) Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: a) They have recovered from the effects of surgery. b) Residual disease following resection of recurrent Glioblastoma is not mandated for eligibility into the study.
14) ( 13. cont'ed) To best assess the extent of residual disease post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to registration. If the 96-hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.
15) Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 42 days from the completion of radiation therapy to study entry.
16) Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, MR spectroscopy or surgical documentation of disease.
17) Women of childbearing potential must have a negative β-HCG pregnancy test documented within 14 days prior to registration.
18) Patients may have had treatment for any number of prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation+/- chemo if that was used as initial therapy).(PhaseI only)
19) Patients may have had treatment for no more than 2 prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation+/- chemo if that was used as initial therapy). The intent therefore is that patients had no more than 3 prior therapies (initial and treatment for 2 relapses). (PhaseII only)
20) (19. cont'd) If the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse. For patients who had prior therapy for a low-Grade glioma, the surgical diagnosis of a glioblastoma will be considered the first relapse. (PhaseII only)
21) For patients enrolled in the Phase II component, it is mandatory that 15 Unstained Paraffin slides or 1 representative tissue block be available from original surgery or definitive surgery or the surgery closest to initiation of this clinical trial.(PhaseII only)
22) Patients must have tissue specimens available and agree to have their blood and tissue blocks (or slides) submitted for the combined correlative studies. Submission of fresh tumor core biopsy specimens is requested, if feasible. (Phase II only) |