Clinical trial NCT00329719 (phase 1/phase 2, status: completed)
Conditions: adult glioblastoma, adult gliosarcoma, recurrent adult brain neoplasm
ICD codes: C71.7, C71.9, C79.31, D33.0, D33.1, D33.2, D49.6
Drugs: sorafenib tosylate, temsirolimus
SMILES: CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1, CN1N=NC2=C(N=CN2C1=O)C(N)=O
Eligibility criteria:

        Inclusion Criteria:

          -  Central pathology review submission; this review is mandatory prior to registration to
             confirm eligibility; it should be initiated as soon after surgery as possible

          -  =< 2 prior systemic chemotherapy regimens

          -  Histological confirmation of a grade 4 astrocytoma (glioblastoma) or gliosarcoma, at
             primary diagnosis or recurrence by World Health Organization (WHO) criteria; central
             pathology review is mandatory prior to study entry to confirm eligibility

          -  Evidence of tumor progression by magnetic resonance imaging (MRI) or computed
             tomography (CT) scan following radiation therapy (RT) or following the most recent
             anti-tumor therapy

          -  Bidimensionally measurable or evaluable disease by MRI or CT scan

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

          -  >= 12 weeks since the completion of RT

          -  Fixed or decreasing dose of corticosteroids (or no corticosteroids) >= 1 week prior to
             registration

          -  >= 1 week from minor surgery other than venous line placement and > 3 weeks from major
             surgery (except for patients undergoing tumor tissue acquisition)

          -  >= 4 weeks since prior cytotoxic chemotherapy (>= 6 weeks for nitrosoureas)

          -  >= 2 weeks from cytostatic chemotherapy such as tamoxifen, cis-retinoic acid, or
             thalidomide (address questions regarding such agents to study chair)

          -  White blood cells (WBC) >= 3,000/mm^3

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin (Hgb) >= 10 gm/dL

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN)

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =<
             2.5 x ULN

          -  Creatinine =< 2.0 x ULN

          -  Serum cholesterol =< 350 mg/dL

          -  Serum triglycerides =< 400 mg/dL

          -  Willingness to provide the biologic specimens as required by the protocol; (please
             note that the willingness to participate pertains only to the patient and does not
             factor in the institution?s ability to participate in any part of the translational
             component)

        Exclusion Criteria:

          -  Prior intratumoral chemotherapy (e.g., Gliadel or IL13-PE38QQR), stereotactic
             radiosurgery, or interstitial brachytherapy unless there is a separate lesion on MRI
             which is not part of the previous treatment field or there is proof of recurrent
             disease based on biopsy, MRI spectroscopy, or positron emission tomography (PET) scan

          -  Prior CCI-779, sorafenib, or other agents specifically targeting mammalian target of
             rapamycin (mTOR) or raf; patients receiving prior agents inhibiting VEGF or VEGF
             receptor (R) (prior anti-VEGF group) are eligible but: 1) must be at least four weeks
             from last treatment with the agent(s); and 2) must have recovered from any clinically
             relevant toxicities attributable to this agent(s)

          -  Evidence of bleeding diathesis or coagulopathy

               -  Note: Patients on prophylactic anticoagulation therapy (e.g., low-dose warfarin)
                  are eligible provided their coagulation parameter levels are as follows:
                  prothrombin time (International Normalized Ratio [INR] of prothrombin time) < 1.1
                  x institutional upper limit of normal

               -  Note: Patients on full-dose anticoagulants (e.g., warfarin) are eligible provided
                  that both of the following criteria are met: a) the patient has an in-range INR
                  (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable
                  dose of low molecular weight heparin, and b) the patient has no active bleeding
                  or pathological condition that carries a high risk of bleeding (e.g., tumor
                  involving major vessels or known varices)

          -  International normalized ration (INR) > 1.5 (unless the patient is on full-dose
             warfarin)

          -  Receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, fosphenytoin,
             carbamazepine, phenobarbital, or primidone) or any other potent cytochrome P450,
             family 3, subfamily A, polypeptide 4 (CYP3A4) inducer, such as rifampin or St. John?s
             wort

          -  Any condition (e.g., gastrointestinal tract disease resulting in an inability to take
             oral medication or a requirement for IV alimentation, prior surgical procedures
             affecting absorption, or active peptic ulcer disease) that impairs their ability to
             swallow pills

          -  Hypertension with systolic blood pressure of > 140 mmHg or diastolic pressure > 90
             mmHg; however, patients with well-controlled hypertension are eligible

          -  Uncontrolled infection

          -  Pregnant women

          -  Nursing women

          -  Men or women of childbearing potential who are unwilling to employ adequate
             contraception

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  Known hypersensitivity to any of the components of CCI-779 or sorafenib

          -  Other active malignancy

          -  Uncontrolled intercurrent illness, including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, psychiatric illness/social situation that would preclude study compliance
             with study requirements

          -  Immunocompromised patients (other than that related to the use of corticosteroids)
             including patients known to be human immunodeficiency virus (HIV) positive;
             HIV-positive patients on combination antiretroviral therapy are ineligible

          -  Receiving any investigational agents other than CCI-779 and sorafenib

          -  Significant intratumoral, intracerebral, or subarachnoid hemorrhage on baseline MRI or
             CT, or other history of significant intratumoral, intracerebral, or subarachnoid
             hemorrhage