Sorafenib and Temsirolimus in Treating Patients With Recurrent Glioblastoma
This trial is active, not recruiting.
|Conditions||adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, recurrent adult brain tumor|
|Treatments||sorafenib tosylate, temsirolimus, conventional surgery|
|Phase||phase 1/phase 2|
|Targets||mTOR, RAF, FLT-3, KIT, PDGF, VEGF|
|Sponsor||National Cancer Institute (NCI)|
|Start date||March 2006|
|End date||February 2013|
|Trial size||115 participants|
|Trial identifier||NCT00329719, CDR0000472240, N0572, NCCTG-N0572, NCI-2009-00652, U10CA025224|
This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with sorafenib and to see how well they work in treating patients with recurrent glioblastoma. Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temsirolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib and temsirolimus may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving sorafenib together with temsirolimus may kill more tumor cells.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Anchorage, AK||Providence Alaska Medical Center||no longer recruiting|
|Scottsdale, AZ||Mayo Clinic in Arizona||no longer recruiting|
|Hartford, CT||Saint Francis Hospital and Medical Center||no longer recruiting|
|Jacksonville, FL||Mayo Clinic in Florida||no longer recruiting|
|Boise, ID||Saint Alphonsus Regional Medical Center||no longer recruiting|
|Aurora, IL||Rush - Copley Medical Center||no longer recruiting|
|Bloomington, IL||Illinois CancerCare-Bloomington||no longer recruiting|
|Bloomington, IL||Saint Joseph Medical Center||no longer recruiting|
|Canton, IL||Graham Hospital Association||no longer recruiting|
|Canton, IL||Illinois CancerCare-Canton||no longer recruiting|
|Carthage, IL||Illinois CancerCare-Carthage||no longer recruiting|
|Carthage, IL||Memorial Hospital||no longer recruiting|
|Chicago, IL||Rush University Medical Center||no longer recruiting|
|Effingham, IL||Saint Anthony Memorial Hospital||no longer recruiting|
|Eureka, IL||Eureka Hospital||no longer recruiting|
|Eureka, IL||Illinois CancerCare-Eureka||no longer recruiting|
|Galesburg, IL||Galesburg Cottage Hospital||no longer recruiting|
|Galesburg, IL||Illinois CancerCare Galesburg||no longer recruiting|
|Havana, IL||Illinois CancerCare-Havana||no longer recruiting|
|Havana, IL||Mason District Hospital||no longer recruiting|
|Hopedale, IL||Hopedale Medical Complex - Hospital||no longer recruiting|
|Joliet, IL||Joliet Oncology-Hematology Associates Limited||no longer recruiting|
|Kewanee, IL||Illinois CancerCare-Kewanee Clinic||no longer recruiting|
|Kewanee, IL||Kewanee Hospital||no longer recruiting|
|Macomb, IL||Illinois CancerCare-Macomb||no longer recruiting|
|Macomb, IL||Mcdonough District Hospital||no longer recruiting|
|Monmouth, IL||Holy Family Medical Center||no longer recruiting|
|Monmouth, IL||Illinois CancerCare-Monmouth||no longer recruiting|
|Normal, IL||Bromenn Regional Medical Center||no longer recruiting|
|Normal, IL||Community Cancer Center Foundation||no longer recruiting|
|Normal, IL||Illinois CancerCare-Community Cancer Center||no longer recruiting|
|Ottawa, IL||Illinois CancerCare-Ottawa Clinic||no longer recruiting|
|Ottawa, IL||Ottawa Regional Hospital and Healthcare Center||no longer recruiting|
|Pekin, IL||Pekin Cancer Treatment Center||no longer recruiting|
|Pekin, IL||Pekin Hospital||no longer recruiting|
|Pekin, IL||Illinois CancerCare-Pekin||no longer recruiting|
|Peoria, IL||Methodist Medical Center of Illinois||no longer recruiting|
|Peoria, IL||Proctor Hospital||no longer recruiting|
|Peoria, IL||Illinois CancerCare-Peoria||no longer recruiting|
|Peoria, IL||Illinois Oncology Research Association CCOP||no longer recruiting|
|Peoria, IL||OSF Saint Francis Medical Center||no longer recruiting|
|Peru, IL||Illinois CancerCare-Peru||no longer recruiting|
|Peru, IL||Illinois Valley Hospital||no longer recruiting|
|Princeton, IL||Illinois CancerCare-Princeton||no longer recruiting|
|Princeton, IL||Perry Memorial Hospital||no longer recruiting|
|Spring Valley, IL||Illinois CancerCare-Spring Valley||no longer recruiting|
|Spring Valley, IL||Saint Margaret's Hospital||no longer recruiting|
|Urbana, IL||Carle Clinic-Urbana Main||no longer recruiting|
|Urbana, IL||Carle Foundation - Carle Cancer Center||no longer recruiting|
|Michigan City, IN||Saint Anthony Memorial Health Center||no longer recruiting|
|Cedar Rapids, IA||Cedar Rapids Oncology Association||no longer recruiting|
|Cedar Rapids, IA||Mercy Hospital||no longer recruiting|
|Cedar Rapids, IA||Oncology Associates at Mercy Medical Center||no longer recruiting|
|Clive, IA||Medical Oncology and Hematology Associates-West Des Moines||no longer recruiting|
|Des Moines, IA||Mercy Capitol||no longer recruiting|
|Des Moines, IA||Iowa Methodist Medical Center||no longer recruiting|
|Des Moines, IA||Iowa Oncology Research Association CCOP||no longer recruiting|
|Des Moines, IA||Medical Oncology and Hematology Associates-Des Moines||no longer recruiting|
|Des Moines, IA||Medical Oncology and Hematology Associates||no longer recruiting|
|Des Moines, IA||Mercy Medical Center - Des Moines||no longer recruiting|
|Des Moines, IA||Iowa Lutheran Hospital||no longer recruiting|
|Mason City, IA||Mercy Medical Center - North Iowa||no longer recruiting|
|Sioux City, IA||Siouxland Hematology Oncology Associates||no longer recruiting|
|Sioux City, IA||Mercy Medical Center-Sioux City||no longer recruiting|
|Sioux City, IA||Saint Luke's Regional Medical Center||no longer recruiting|
|Anthony, KS||Hospital District Sixth of Harper County||no longer recruiting|
|Chanute, KS||Cancer Center of Kansas - Chanute||no longer recruiting|
|Dodge City, KS||Cancer Center of Kansas - Dodge City||no longer recruiting|
|El Dorado, KS||Cancer Center of Kansas - El Dorado||no longer recruiting|
|Fort Scott, KS||Cancer Center of Kansas - Fort Scott||no longer recruiting|
|Independence, KS||Cancer Center of Kansas-Independence||no longer recruiting|
|Kingman, KS||Cancer Center of Kansas-Kingman||no longer recruiting|
|Lawrence, KS||Lawrence Memorial Hospital||no longer recruiting|
|Liberal, KS||Cancer Center of Kansas-Liberal||no longer recruiting|
|McPherson, KS||Cancer Center of Kansas - McPherson||no longer recruiting|
|Newton, KS||Cancer Center of Kansas - Newton||no longer recruiting|
|Parsons, KS||Cancer Center of Kansas - Parsons||no longer recruiting|
|Pratt, KS||Cancer Center of Kansas - Pratt||no longer recruiting|
|Salina, KS||Cancer Center of Kansas - Salina||no longer recruiting|
|Wellington, KS||Cancer Center of Kansas - Wellington||no longer recruiting|
|Wichita, KS||Associates In Womens Health||no longer recruiting|
|Wichita, KS||Cancer Center of Kansas-Wichita Medical Arts Tower||no longer recruiting|
|Wichita, KS||Cancer Center of Kansas - Main Office||no longer recruiting|
|Wichita, KS||Via Christi Regional Medical Center||no longer recruiting|
|Wichita, KS||Wichita CCOP||no longer recruiting|
|Winfield, KS||Cancer Center of Kansas - Winfield||no longer recruiting|
|Ann Arbor, MI||Saint Joseph Mercy Hospital||no longer recruiting|
|Ann Arbor, MI||Michigan Cancer Research Consortium Community Clinical Oncology Program||no longer recruiting|
|Battle Creek, MI||Bronson Battle Creek||no longer recruiting|
|Big Rapids, MI||Mecosta County Medical Center||no longer recruiting|
|Dearborn, MI||Oakwood Hospital||no longer recruiting|
|Detroit, MI||Saint John Hospital and Medical Center||no longer recruiting|
|Escanaba, MI||Green Bay Oncology - Escanaba||no longer recruiting|
|Flint, MI||Hurley Medical Center||no longer recruiting|
|Flint, MI||Genesys Hurley Cancer Institute||no longer recruiting|
|Grand Rapids, MI||Grand Rapids Clinical Oncology Program||no longer recruiting|
|Grand Rapids, MI||Saint Mary's Health Care||no longer recruiting|
|Grand Rapids, MI||Spectrum Health at Butterworth Campus||no longer recruiting|
|Iron Mountain, MI||Green Bay Oncology - Iron Mountain||no longer recruiting|
|Jackson, MI||Allegiance Health||no longer recruiting|
|Lansing, MI||Sparrow Hospital||no longer recruiting|
|Livonia, MI||Saint Mary Mercy Hospital||no longer recruiting|
|Muskegon, MI||Mercy Health Partners-Mercy Campus||no longer recruiting|
|Pontiac, MI||Saint Joseph Mercy Oakland||no longer recruiting|
|Port Huron, MI||Saint Joseph Mercy Port Huron||no longer recruiting|
|Saginaw, MI||Saint Mary's of Michigan||no longer recruiting|
|Traverse City, MI||Munson Medical Center||no longer recruiting|
|Warren, MI||Saint John Macomb-Oakland Hospital||no longer recruiting|
|Wyoming, MI||Metro Health Hospital||no longer recruiting|
|Alexandria, MN||Medini, Eitan MD (UIA Investigator)||no longer recruiting|
|Bemidji, MN||Sanford Clinic North-Bemidgi||no longer recruiting|
|Burnsville, MN||Fairview Ridges Hospital||no longer recruiting|
|Coon Rapids, MN||Mercy Hospital||no longer recruiting|
|Duluth, MN||Essentia Health Duluth Clinic CCOP||no longer recruiting|
|Duluth, MN||Essentia Health Saint Mary's Medical Center||no longer recruiting|
|Duluth, MN||Miller-Dwan Hospital||no longer recruiting|
|Edina, MN||Fairview-Southdale Hospital||no longer recruiting|
|Fridley, MN||Unity Hospital||no longer recruiting|
|Hutchinson, MN||Hutchinson Area Health Care||no longer recruiting|
|Maplewood, MN||Minnesota Oncology Hematology PA-Maplewood||no longer recruiting|
|Maplewood, MN||Saint John's Hospital - Healtheast||no longer recruiting|
|Minneapolis, MN||Abbott-Northwestern Hospital||no longer recruiting|
|Minneapolis, MN||Hennepin County Medical Center||no longer recruiting|
|New Ulm, MN||New Ulm Medical Center||no longer recruiting|
|Robbinsdale, MN||North Memorial Medical Health Center||no longer recruiting|
|Rochester, MN||Mayo Clinic||no longer recruiting|
|Rochester, MN||North Central Cancer Treatment Group||no longer recruiting|
|Saint Cloud, MN||CentraCare Clinic||no longer recruiting|
|Saint Cloud, MN||Saint Cloud Hospital||no longer recruiting|
|Saint Louis Park, MN||Metro-Minnesota CCOP||no longer recruiting|
|Saint Louis Park, MN||Park Nicollet Clinic - Saint Louis Park||no longer recruiting|
|Saint Paul, MN||Regions Hospital||no longer recruiting|
|Saint Paul, MN||United Hospital||no longer recruiting|
|Shakopee, MN||Saint Francis Regional Medical Center||no longer recruiting|
|Stillwater, MN||Lakeview Hospital||no longer recruiting|
|Waconia, MN||Ridgeview Medical Center||no longer recruiting|
|Willmar, MN||Rice Memorial Hospital||no longer recruiting|
|Woodbury, MN||Minnesota Oncology and Hematology PA-Woodbury||no longer recruiting|
|Lincoln, NE||Lincoln Medical Education Foundation Cancer Resource Center||no longer recruiting|
|Omaha, NE||Missouri Valley Cancer Consortium CCOP||no longer recruiting|
|Omaha, NE||Alegent Health Immanuel Medical Center||no longer recruiting|
|Omaha, NE||Alegent Health Bergan Mercy Medical Center||no longer recruiting|
|Omaha, NE||Alegent Health Lakeside Hospital||no longer recruiting|
|Omaha, NE||Creighton University Medical Center||no longer recruiting|
|Rutherfordton, NC||Rutherford Hospital||no longer recruiting|
|Bismarck, NC||Mid Dakota Clinic||no longer recruiting|
|Bismarck, NC||Saint Alexius Medical Center||no longer recruiting|
|Bismarck, NC||Sanford Bismarck Medical Center||no longer recruiting|
|Fargo, NC||Roger Maris Cancer Center||no longer recruiting|
|Fargo, NC||Sanford Clinic North-Fargo||no longer recruiting|
|Fargo, NC||Sanford Medical Center-Fargo||no longer recruiting|
|Grand Forks, NC||Altru Cancer Center||no longer recruiting|
|Allentown, PA||Lehigh Valley Hospital||no longer recruiting|
|Bethlehem, PA||Lehigh Valley Hospital - Muhlenberg||no longer recruiting|
|Danville, PA||Geisinger Medical Center||no longer recruiting|
|Hazleton, PA||Geisinger Medical Center-Cancer Center Hazelton||no longer recruiting|
|State College, PA||Geisinger Medical Group||no longer recruiting|
|Wilkes-Barre, PA||Geisinger Wyoming Valley||no longer recruiting|
|Anderson, SC||AnMed Health Cancer Center||no longer recruiting|
|Greenville, SC||Saint Francis Hospital||no longer recruiting|
|Spartanburg, SC||Spartanburg Regional Medical Center||no longer recruiting|
|Spartanburg, SC||Upstate Carolina CCOP||no longer recruiting|
|Rapid City, SD||Rapid City Regional Hospital||no longer recruiting|
|Sioux Falls, SD||Avera Cancer Institute||no longer recruiting|
|Sioux Falls, SD||Avera McKennan Hospital and University Health Center||no longer recruiting|
|Charlottesville, VA||University of Virginia||no longer recruiting|
|Richmond, VA||Virginia Commonwealth University||no longer recruiting|
|Green Bay, WI||Green Bay Oncology at Saint Vincent Hospital||no longer recruiting|
|Green Bay, WI||Saint Vincent Hospital||no longer recruiting|
|Green Bay, WI||Green Bay Oncology Limited at Saint Mary's Hospital||no longer recruiting|
|Green Bay, WI||Saint Mary's Hospital||no longer recruiting|
|Manitowoc, WI||Holy Family Memorial Hospital||no longer recruiting|
|Marinette, WI||Bay Area Medical Center||no longer recruiting|
|Oconto Falls, WI||Green Bay Oncology - Oconto Falls||no longer recruiting|
|Sheboygan, WI||Saint Nicholas Hospital||no longer recruiting|
|Sturgeon Bay, WI||Green Bay Oncology - Sturgeon Bay||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||parallel assignment|
time frame: At 6 months
time frame: From start of study registration to death due to any cause or until last follow-up, up to 5 years
Objective Response, as Determined by a Neurological Exam, MRI, and/or CT Measurement
time frame: Up to 5 years
time frame: Time from study registration to date of disease progression or last follow-up, assessed up to 5 years
Male or female participants at least 18 years old.
- Central pathology review submission prior to registration to confirm eligibility. It should be initiated as soon after surgery as possible.
- ≤2 prior systemic chemotherapy regimens.
- ≥18 years of age.
- 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 Computerized 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.
- ≥4 weeks from prior cytotoxic chemotherapy (≥6 weeks for nitrosoureas).
- ≥2 weeks from cytostatic chemotherapy such as tamoxifen, cis-retinoic acid, or thalidomide.
- The following laboratory values obtained ≤7 days prior to registration:
- WBC ≥3000/mm3
- ANC ≥1500/mm3
- PLT ≥100,000/mm3
- Hgb ≥10 gm/dL
- Total bilirubin ≤1.5 x ULN
- SGOT (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.)
- 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 mTOR or raf. Patients receiving prior agents inhibiting VEGF or VEGFR (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 (INR; International Normalized Ratio 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).
- 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 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.
- Any of the following because temsirolimus and sorafenib are investigational agents whose genotoxic effects on the developing fetus and newborn are unknown:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Known hypersensitivity to any of the components of temsirolimus 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, or psychiatric illness/social situations that would limit compliance with study requirements.
- Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with temsirolimus and sorafenib.
- Receiving any investigational agents other than temsirolimus and sorafenib.
- Significant intratumoral, intracerebral, or subarachnoid hemorrhage on baseline MRI or CT, or other history of significant intratumoral, intracerebral, or subarachnoid hemorrhage.
|Official title||A Phase I/II Trial of Sorafenib and CCI-779 in Patients With Recurrent Glioblastoma|
|Principal investigator||Kurt Jaeckle|
|Description||Primary Objective - Phase I (closed to accrual as of 01/11/2008): To establish a maximum tolerable dose of temsirolimus in combination with sorafenib in patients with recurrent glioblastoma not receiving enzyme-inducing anticonvulsants (EIACs). Phase II (closed to accrual as of 12/07/2012): To assess the efficacy of temsirolimus and sorafenib in the treatment of recurrent glioblastoma in non-EIAC patients as measured by progression-free survival status at six months (PFS6). Secondary Objectives - Phase I (closed to accrual as of 01/11/2008): I. To define the safety profile of temsirolimus and sorafenib in non-EIAC patients. II. To assess the evidence of antitumor activity. Phase II (closed to accrual as of 12/07/2012): I. To assess the safety and toxicities of temsirolimus and sorafenib in the above-noted patient populations. Outline: This is a multicenter, phase I, dose-escalation study followed by a phase II study. Phase I (Arm A): Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II: Patients are assigned to 1 of 3 treatment groups. Group 1 (Arm B): Patients receive sorafenib and temsirolimus as in phase I at the MTD. (patients not undergoing surgery) Group 2 (Arm C): Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. (patients undergoing surgery) After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD. Group 3 (Arm D): Patient receive sorafenib and temsirolimus as in phase I at the MTD. (patients who have received prior anti-vascular endothelial growth factor [VEGF] therapy and are not undergoing surgery) Biopsy or resected tissue and blood are collected prior to treatment (usually at diagnosis) and analyzed for biomarkers. After completion of study treatment, patients are followed every 6 months for 5 years and then annually thereafter.|
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