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A Phase I/II Trial of Sorafenib and CCI-779 in Patients With Recurrent Glioblastoma


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

Thank you

Trial Information

A Phase I/II Trial of Sorafenib and CCI-779 in Patients With Recurrent Glioblastoma


PRIMARY OBJECTIVES:

I. Establish a maximum tolerable dose of temsirolimus in combination with sorafenib in
patients with recurrent glioblastoma not receiving enzyme-inducing anticonvulsants (EIACs).
(Phase I [closed to accrual as of 11/21/07]) II. Define the safety profile of temsirolimus
and sorafenib in these patients. (Phase I [closed to accrual as of 11/21/07]) III. Assess
the evidence of antitumor activity. (Phase I [closed to accrual as of 11/21/07])Assess the
efficacy, as measured by progression-free survival, of temsirolimus and sorafenib in
patients with recurrent glioblastoma not receiving EIACs. (Phase II) IV. Assess the safety
and toxicities of this regimen in these patients. (Phase II)

SECONDARY OBJECTIVES:

I. Correlate tumor and blood biomarkers with clinical outcome of patients treated with
temsirolimus and sorafenib.

II. Evaluate tumor tissue specimens for evidence of bioactivity of these agents.

OUTLINE: This is a multicenter, phase I (closed to accrual as of 11/21/07), dose-escalation
study of temsirolimus followed by a phase II open-label study.

PHASE I: 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. (closed to accrual
as of 11/21/07) 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: Patients receive sorafenib and temsirolimus as in phase I (closed to accrual as of
11/21/07) at the MTD. (patients not undergoing surgery)

GROUP 2: 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 (closed
to accrual as of 11/21/07) at the MTD.

GROUP 3: Patient receive sorafenib and temsirolimus as in phase I (closed to accrual as of
11/21/07) 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.


Inclusion Criteria:



- Histologically confirmed grade IV astrocytoma (glioblastoma) or gliosarcoma

- Evidence of tumor progression by magnetic resonance imaging (MRI) or computed
tomography (CT) scan after prior radiotherapy or most recent antitumor therapy

- Bidimensionally measurable or evaluable disease by MRI or CT scan

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

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

- Absolute neutrophil count ≥ 1,500/mm^3

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

- Hemoglobin >= 10 g/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

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

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for 6 months after
completion of study therapy

- No human immunodeficiency virus (HIV) positivity

- No evidence of bleeding diathesis or coagulopathy

- No condition (e.g., gastrointestinal tract disease resulting in an inability to take
oral medication, requirement for IV alimentation, or active peptic ulcer disease)
that would impair the ability to swallow pills

- No uncontrolled hypertension with systolic blood pressure (BP) > 140 mm Hg or
diastolic BP pressure> 90 mm Hg

- No uncontrolled infection

- No known hypersensitivity to any of the components of temsirolimus or sorafenib

- No immunocompromised patients (other than that related to the use of corticosteroids)

- No other active malignancy

- No uncontrolled intercurrent illness, including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situation that would preclude study compliance

- No significant intratumoral, intracerebral, or subarachnoid hemorrhage on baseline
MRI or CT scan

- No other history of significant intratumoral, intracerebral, or subarachnoid
hemorrhage

- Concurrent full-dose anticoagulants (e.g., warfarin) allowed provided all of the
following criteria are met:

- In-range INR(between 2 and 3) on a stable dose of oral anticoagulant or on a
stabledose of low molecular weight heparin

- No active bleedingor pathological condition that carries a high risk of bleeding
(e.g., tumorinvolving major vessels or known varices)

- At least 12 weeks since prior radiotherapy

- At least 4 weeks since prior temsirolimus, sorafenib, or other agents specifically
targeting mTOR, raf, or vascular endothelial growth factor (VEGF)/VEGF receptors and
recovered

- At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas)

- At least 2 weeks since prior cytostatic chemotherapy (e.g., tamoxifen, isotretinoin,
or thalidomide)

- At least 1 week since prior fixed or decreasing dose of corticosteroids (or no
corticosteroids)

- At least 1 week since prior minor surgery other than venous line placement (3 weeks
for major surgery)

- No more than 2 prior systemic chemotherapy regimens

- No prior surgical procedures affecting absorption

- No prior intratumoral chemotherapy (e.g., polifeprosan 20 with carmustine implant or
cintredekin besudotox), stereotactic radiosurgery, or interstitial brachytherapy
unless there is a separate lesion on MRI that is not part of the previous treatment
field or there is proof of recurrent disease based on biopsy, MRI spectroscopy, or
positron emission tomography scan

- No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin,fosphenytoin,
carbamazepine, phenobarbital, or primidone) or any other potent CYP3A4 inducer, such
as rifampin or Hypericum perforatum (St. John's wort)

- No other concurrent investigational agents

- No concurrent prophylactic hematopoietic colony-stimulating factors

- No other concurrent anticancer agents or therapies

- Concurrent prophylactic anticoagulation therapy (e.g., low-dosewarfarin) allowed
provided coagulation parameter levels (prothrombin time [INR]) < 1.1 times upper
limit of normal (ULN)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Description:

The âsuccessâ probability, i.e., 6-month progression-free survival percentage, for each of group 1 and group 3 will be estimated as the number of evaluable patients still alive at 6 months divided by the total number of evaluable patients followed for at least 6 months. Ninety percent confidence intervals for the âsuccessâ probability will be calculated according to the approach of Duffy and Santner.

Outcome Time Frame:

At 6 months

Safety Issue:

No

Principal Investigator

Kurt Jaeckle

Investigator Role:

Principal Investigator

Investigator Affiliation:

North Central Cancer Treatment Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00652

NCT ID:

NCT00329719

Start Date:

March 2006

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
  • Brain Neoplasms
  • Glioblastoma
  • Gliosarcoma

Name

Location

Mayo Clinic Rochester, Minnesota  55905
Hurley Medical Center Flint, Michigan  48503
Genesys Hurley Cancer Institute Flint, Michigan  48503
Fairview Ridges Hospital Burnsville, Minnesota  55337
Hutchinson Area Health Care Hutchinson, Minnesota  55350
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Geisinger Medical Center Danville, Pennsylvania  17822-0001
Avera Cancer Institute Sioux Falls, South Dakota  57105
CentraCare Clinic Saint Cloud, Minnesota  56303
Rapid City Regional Hospital Rapid City, South Dakota  57709
Methodist Medical Center of Illinois Peoria, Illinois  61636
Lehigh Valley Hospital Allentown, Pennsylvania  18103
Rush University Medical Center Chicago, Illinois  60612-3824
Providence Alaska Medical Center Anchorage, Alaska  99508
Via Christi Regional Medical Center Wichita, Kansas  67214
Iowa Methodist Medical Center Des Moines, Iowa  50309
Iowa Lutheran Hospital Des Moines, Iowa  50316-2301
Cancer Center of Kansas - Chanute Chanute, Kansas  66720
Cancer Center of Kansas - Dodge City Dodge City, Kansas  67801
Cancer Center of Kansas - Newton Newton, Kansas  67114
Cancer Center of Kansas - Salina Salina, Kansas  67042
Cancer Center of Kansas - Wellington Wellington, Kansas  67152
Associates in Womens Health Wichita, Kansas  67203
Cancer Center of Kansas - Winfield Winfield, Kansas  67156
Munson Medical Center Traverse City, Michigan  49684
Avera McKennan Hospital and University Health Center Sioux Falls, South Dakota  57105
Memorial Hospital Carthage, Illinois  62321
Galesburg Cottage Hospital Galesburg, Illinois  61401
Mason District Hospital Havana, Illinois  62644
Kewanee Hospital Kewanee, Illinois  61443
McDonough District Hospital Macomb, Illinois  61455
BroMenn Regional Medical Center Normal, Illinois  61761
Proctor Hospital Peoria, Illinois  61614
Perry Memorial Hospital Princeton, Illinois  61356
Mecosta County Medical Center Big Rapids, Michigan  49307
Creighton University Medical Center Omaha, Nebraska  68131-2197
Eureka Hospital Eureka, Illinois  61530
Mercy Hospital Coon Rapids, Minnesota  55433
Graham Hospital Association Canton, Illinois  61520
Holy Family Medical Center Des Plaines, Illinois  60016
Saint Joseph Medical Center Joliet, Illinois  60435
Pekin Hospital Pekin, Illinois  61554
Medical Oncology and Hematology Associates Des Moines, Iowa  50309
Saint Joseph Mercy Hospital Ann Arbor, Michigan  48106
Fairview-Southdale Hospital Edina, Minnesota  55435
Abbott-Northwestern Hospital Minneapolis, Minnesota  55407
Regions Hospital Saint Paul, Minnesota  55101
Saint Francis Regional Medical Center Shakopee, Minnesota  55379
Rice Memorial Hospital Willmar, Minnesota  56201
Altru Cancer Center Grand Forks, North Dakota  58206
Geisinger Medical Group State College, Pennsylvania  16801
Spartanburg Regional Medical Center Spartanburg, South Carolina  29303
Hospital District Sixth of Harper County Anthony, Kansas  67003
Cancer Center of Kansas - Fort Scott Fort Scott, Kansas  66701
Cancer Center of Kansas-Independence Independence, Kansas  67301
Lawrence Memorial Hospital Lawrence, Kansas  66044
Lehigh Valley Hospital - Muhlenberg Bethlehem, Pennsylvania  18017
Rutherford Hospital Rutherfordton, North Carolina  28139
AnMed Health Cancer Center Anderson, South Carolina  29621
Mayo Clinic in Arizona Scottsdale, Arizona  85259-5404
Mayo Clinic in Florida Jacksonville, Florida  32224
Metro Health Hospital Grand Rapids, Michigan  49506
University of Virginia Charlottesville, Virginia  22908
Hennepin County Medical Center Minneapolis, Minnesota  
Saint Alphonsus Regional Medical Center Boise, Idaho  83706
Cancer Center of Kansas - McPherson McPherson, Kansas  67460
Mid Dakota Clinic Bismarck, North Dakota  58501
Wichita CCOP Wichita, Kansas  67214-3882
Alegent Health Immanuel Medical Center Omaha, Nebraska  68122
Alegent Health Bergan Mercy Medical Center Omaha, Nebraska  68124
Metro-Minnesota CCOP St. Louis Park, Minnesota  
Lakeview Hospital Stillwater, Minnesota  55082
Virginia Commonwealth University Richmond, Virginia  
New Ulm Medical Center New Ulm, Minnesota  56073
OSF Saint Francis Medical Center Peoria, Illinois  61637
Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
Rush - Copley Medical Center Aurora, Illinois  60504
Saint Anthony Memorial Hospital Effingham, Illinois  62401
Hopedale Medical Complex - Hospital Hopedale, Illinois  61747
Joliet Oncology-Hematology Associates Limited Joliet, Illinois  60435
Community Cancer Center Foundation Normal, Illinois  61761
Illinois CancerCare-Ottawa Clinic Ottawa, Illinois  61350
Ottawa Regional Hospital and Healthcare Center Ottawa, Illinois  61350
Pekin Cancer Treatment Center Pekin, Illinois  61554
Illinois Oncology Research Association CCOP Peoria, Illinois  61615
Illinois CancerCare-Peoria Peoria, Illinois  61615
Illinois Valley Hospital Peru, Illinois  61354
Saint Margaret's Hospital Spring Valley, Illinois  61362
Carle Clinic-Urbana Main Urbana, Illinois  61801
Saint Anthony Memorial Health Center Michigan City, Indiana  46360
Cedar Rapids Oncology Association Cedar Rapids, Iowa  52403
Mercy Hospital Cedar Rapids, Iowa  52403
Medical Oncology and Hematology Associates-West Des Moines Clive, Iowa  50325
Iowa Oncology Research Association CCOP Des Moines, Iowa  50309
Mercy Capitol Des Moines, Iowa  50307
Mercy Medical Center - Des Moines Des Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des Moines Des Moines, Iowa  50309
Mercy Medical Center - North Iowa Mason City, Iowa  50401
Mercy Medical Center-Sioux City Sioux City, Iowa  51104
Saint Luke's Regional Medical Center Sioux City, Iowa  51104
Cancer Center of Kansas - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas-Kingman Kingman, Kansas  67068
Cancer Center of Kansas - Parsons Parsons, Kansas  67357
Cancer Center of Kansas - Pratt Pratt, Kansas  67124
Cancer Center of Kansas-Wichita Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas - Main Office Wichita, Kansas  67214
Michigan Cancer Research Consortium Community Clinical Oncology Program Ann Arbor, Michigan  48106
Oakwood Hospital Dearborn, Michigan  48123
Saint John Hospital and Medical Center Detroit, Michigan  48236
Green Bay Oncology - Escanaba Escanaba, Michigan  49431
Grand Rapids Clinical Oncology Program Grand Rapids, Michigan  49503
Saint Mary's Health Care Grand Rapids, Michigan  49503
Spectrum Health at Butterworth Campus Grand Rapids, Michigan  49503
Green Bay Oncology - Iron Mountain Iron Mountain, Michigan  49801
Allegiance Health Jackson, Michigan  49201
Sparrow Hospital Lansing, Michigan  48912
Saint Mary Mercy Hospital Livonia, Michigan  48154
Mercy Health Partners-Mercy Campus Muskegon, Michigan  49443
Saint Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Saint Joseph Mercy Port Huron Port Huron, Michigan  48060
Saint Mary's of Michigan Saginaw, Michigan  48601
Saint John Macomb-Oakland Hospital Warren, Michigan  48093
Medini, Eitan MD (UIA Investigator) Alexandria, Minnesota  56308
Miller-Dwan Hospital Duluth, Minnesota  55805
Unity Hospital Fridley, Minnesota  55432
Saint John's Hospital - Healtheast Maplewood, Minnesota  55109
Minnesota Oncology Hematology PA-Maplewood Maplewood, Minnesota  55109
North Memorial Medical Health Center Robbinsdale, Minnesota  55422
Saint Cloud Hospital Saint Cloud, Minnesota  56303
Park Nicollet Clinic - Saint Louis Park Saint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-Woodbury Woodbury, Minnesota  55125
Lincoln Medical Education Foundation Cancer Resource Center Lincoln, Nebraska  68510
Missouri Valley Cancer Consortium CCOP Omaha, Nebraska  68106
Saint Alexius Medical Center Bismarck, North Dakota  58501
Geisinger Wyoming Valley Wilkes-Barre, Pennsylvania  18711
Upstate Carolina CCOP Spartanburg, South Carolina  29303
Saint Vincent Hospital Green Bay, Wisconsin  54301
Green Bay Oncology Limited at Saint Mary's Hospital Green Bay, Wisconsin  54303
Saint Mary's Hospital Green Bay, Wisconsin  54303
Green Bay Oncology at Saint Vincent Hospital Green Bay, Wisconsin  54301-3526
Bay Area Medical Center Marinette, Wisconsin  54143
Green Bay Oncology - Oconto Falls Oconto Falls, Wisconsin  54154
Green Bay Oncology - Sturgeon Bay Sturgeon Bay, Wisconsin  54235
Roger Maris Cancer Center Fargo, North Dakota  58122
Illinois CancerCare-Bloomington Bloomington%, Illinois  61701
Illinois CancerCare-Canton Canton, Illinois  61520
Illinois CancerCare-Carthage Carthage, Illinois  62321
Illinois CancerCare-Eureka Eureka, Illinois  61530
Illinois CancerCare-Havana Havana, Illinois  62644
Illinois CancerCare-Kewanee Clinic Kewanee, Illinois  61443
Illinois CancerCare-Macomb Macomb, Illinois  61455
Illinois CancerCare-Monmouth Monmouth, Illinois  61462
Illinois CancerCare-Community Cancer Center Normal, Illinois  61761
Illinois CancerCare-Pekin Pekin, Illinois  61603
Illinois CancerCare-Peru Peru, Illinois  61354
Illinois CancerCare-Princeton Princeton, Illinois  61356
Illinois CancerCare-Spring Valley Spring Valley, Illinois  61362
Cancer Center of Kansas-Liberal Liberal, Kansas  67901
Holy Family Memorial Hospital Manitowoc, Wisconsin  54221
Saint Francis Hospital Greenville, South Carolina  29601
Saint Nicholas Hospital Madison, Wisconsin  53715
Alegent Health Lakeside Hospital Omaha, Nebraska  68130
Siouxland Hematology Oncology Associates Sioux City, Iowa  51101
Carle Foundation - Carle Cancer Center Urbana, Illinois  61801
Oncology Associates at Mercy Medical Center Cedar Rapids, Iowa  52403
Sanford Clinic North-Fargo Fargo, North Dakota  58102
Sanford Medical Center-Fargo Fargo, North Dakota  58122
North Central Cancer Treatment Group Rochester, Minnesota  55905
Sanford Clinic North-Bemidgi Bemidji, Minnesota  56601
Essentia Health Duluth Clinic CCOP Duluth, Minnesota  55805
Essentia Health Saint Mary's Medical Center Duluth, Minnesota  55805
Sanford Bismarck Medical Center Bismarck, North Dakota  58501
Geisinger Medical Center-Cancer Center Hazelton Hazleton, Pennsylvania  18201
Illinois CancerCare Galesburg Galesburg, Illinois  61401
Bronson Battle Creek Battle Creek, Michigan  49017