Sorafenib Tosylate and Temsirolimus in Treating Patients With Recurrent Glioblastoma
Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Neoplasm
About this trial
This is an interventional treatment trial for Adult Glioblastoma
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
Sites / Locations
- Providence Alaska Medical Center
- Mayo Clinic in Arizona
- Smilow Cancer Hospital Care Center at Saint Francis
- Mayo Clinic in Florida
- Saint Alphonsus Cancer Care Center-Boise
- Rush - Copley Medical Center
- Saint Joseph Medical Center
- Illinois CancerCare-Bloomington
- Graham Hospital Association
- Illinois CancerCare-Canton
- Illinois CancerCare-Carthage
- Memorial Hospital
- Rush University Medical Center
- Heartland Cancer Research NCORP
- Saint Anthony Memorial Hospital
- Eureka Hospital
- Illinois CancerCare-Eureka
- Galesburg Cottage Hospital
- Illinois CancerCare-Galesburg
- Illinois CancerCare-Havana
- Mason District Hospital
- Hopedale Medical Complex - Hospital
- Joliet Oncology-Hematology Associates Limited
- Illinois CancerCare-Kewanee Clinic
- Kewanee Hospital
- Illinois CancerCare-Macomb
- Mcdonough District Hospital
- Holy Family Medical Center
- Illinois CancerCare-Monmouth
- Bromenn Regional Medical Center
- Community Cancer Center Foundation
- Illinois CancerCare-Community Cancer Center
- Illinois CancerCare-Ottawa Clinic
- Ottawa Regional Hospital and Healthcare Center
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Pekin Hospital
- Methodist Medical Center of Illinois
- Proctor Hospital
- Illinois CancerCare-Peoria
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Illinois Valley Hospital
- Illinois CancerCare-Princeton
- Perry Memorial Hospital
- Illinois CancerCare-Spring Valley
- Saint Margaret's Hospital
- Carle Cancer Center
- The Carle Foundation Hospital
- Franciscan Saint Anthony Health-Michigan City
- McFarland Clinic PC-William R Bliss Cancer Center
- Mercy Hospital
- Oncology Associates at Mercy Medical Center
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Capitol
- Iowa Methodist Medical Center
- Iowa-Wide Oncology Research Coalition NCORP
- Medical Oncology and Hematology Associates-Des Moines
- Medical Oncology and Hematology Associates-Laurel
- Mercy Medical Center - Des Moines
- Iowa Lutheran Hospital
- Mercy Medical Center - North Iowa
- Siouxland Regional Cancer Center
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- Hospital District Sixth of Harper County
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Southwest Medical Center
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas - McPherson
- Cancer Center of Kansas - Newton
- Cancer Center of Kansas - Parsons
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Cancer Center of Kansas - Wellington
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Cancer Center of Kansas - Wichita
- Via Christi Regional Medical Center
- Wichita NCI Community Oncology Research Program
- Cancer Center of Kansas - Winfield
- Michigan Cancer Research Consortium NCORP
- Saint Joseph Mercy Hospital
- Bronson Battle Creek
- Spectrum Health Big Rapids Hospital
- Beaumont Hospital-Dearborn
- Saint John Hospital and Medical Center
- Green Bay Oncology - Escanaba
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Genesys Regional Medical Center-West Flint Campus
- Cancer Research Consortium of West Michigan NCORP
- Mercy Health Saint Mary's
- Spectrum Health at Butterworth Campus
- Green Bay Oncology - Iron Mountain
- Allegiance Health
- Sparrow Hospital
- Saint Mary Mercy Hospital
- Mercy Health Mercy Campus
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- Saint Mary's of Michigan
- Munson Medical Center
- Saint John Macomb-Oakland Hospital
- Metro Health Hospital
- Medini, Eitan MD (UIA Investigator)
- Sanford Clinic North-Bemidgi
- Fairview Ridges Hospital
- Mercy Hospital
- Essentia Health Cancer Center
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Fairview-Southdale Hospital
- Etzell, Paul S MD (UIA Investigator)
- Lake Region Healthcare Corporation-Cancer Care
- Swenson, Wade II, MD (UIA Investigator)
- Unity Hospital
- Hutchinson Area Health Care
- Meeker County Memorial Hospital
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Minnesota Cooperative Group Outreach Program
- Virginia Piper Cancer Institute
- Hennepin County Medical Center
- New Ulm Medical Center
- North Memorial Medical Health Center
- Mayo Clinic
- Coborn Cancer Center at Saint Cloud Hospital
- Saint Cloud Hospital
- Metro Minnesota Community Oncology Research Consortium
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- Saint Joseph's Hospital - Healtheast
- United Hospital
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Woodwinds Health Campus
- Nebraska Cancer Research Center
- Missouri Valley Cancer Consortium
- Alegent Health Immanuel Medical Center
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- Rutherford Hospital
- Southeast Clinical Oncology Research (SCOR) Consortium NCORP
- Mid Dakota Clinic
- Saint Alexius Medical Center
- Sanford Bismarck Medical Center
- Roger Maris Cancer Center
- Sanford Broadway Medical Center
- Sanford Clinic North-Fargo
- Altru Cancer Center
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- Geisinger Medical Center
- Geisinger Medical Center-Cancer Center Hazleton
- Geisinger Medical Group
- Geisinger Wyoming Valley/Henry Cancer Center
- AnMed Health Cancer Center
- AnMed Health Hospital
- Saint Francis Hospital
- Spartanburg Medical Center
- Rapid City Regional Hospital
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Avera McKennan Hospital and University Health Center
- Medical X-Ray Center
- Sanford USD Medical Center - Sioux Falls
- University of Virginia Cancer Center
- Virginia Commonwealth University/Massey Cancer Center
- Virginia Mason Medical Center
- Green Bay Oncology at Saint Vincent Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Green Bay Oncology Limited at Saint Mary's Hospital
- Saint Vincent Hospital Cancer Center at Saint Mary's
- Holy Family Memorial Hospital
- Bay Area Medical Center
- Green Bay Oncology - Oconto Falls
- HSHS Saint Nicholas Hospital
- Green Bay Oncology - Sturgeon Bay
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Group I (sorafenib tosylate, temsirolimus)
Group II (sorafenib tosylate, temsirolimus, surgery)
Group III (sorafenib tosylate, temsirolimus, anti-VEGF)
Patients receive sorafenib tosylate and temsirolimus as in Phase I.
Patients receive sorafenib tosylate PO BID on days 1-8 and temsirolimus IV over 30 minutes on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib tosylate and temsirolimus as in Phase I.
Patients who have received prior anti-VEGF therapy and are not undergoing surgery receive sorafenib tosylate and temsirolimus as in Phase I.