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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 ClinicRochester, Minnesota  55905
Hurley Medical CenterFlint, Michigan  48503
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Fairview Ridges HospitalBurnsville, Minnesota  55337
Hutchinson Area Health CareHutchinson, Minnesota  55350
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Avera Cancer InstituteSioux Falls, South Dakota  57105
CentraCare ClinicSaint Cloud, Minnesota  56303
Rapid City Regional HospitalRapid City, South Dakota  57709
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Lehigh Valley HospitalAllentown, Pennsylvania  18103
Rush University Medical CenterChicago, Illinois  60612-3824
Providence Alaska Medical CenterAnchorage, Alaska  99508
Via Christi Regional Medical CenterWichita, Kansas  67214
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Cancer Center of Kansas - ChanuteChanute, Kansas  66720
Cancer Center of Kansas - Dodge CityDodge City, Kansas  67801
Cancer Center of Kansas - NewtonNewton, Kansas  67114
Cancer Center of Kansas - SalinaSalina, Kansas  67042
Cancer Center of Kansas - WellingtonWellington, Kansas  67152
Associates in Womens HealthWichita, Kansas  67203
Cancer Center of Kansas - WinfieldWinfield, Kansas  67156
Munson Medical CenterTraverse City, Michigan  49684
Avera McKennan Hospital and University Health CenterSioux Falls, South Dakota  57105
Memorial HospitalCarthage, Illinois  62321
Galesburg Cottage HospitalGalesburg, Illinois  61401
Mason District HospitalHavana, Illinois  62644
Kewanee HospitalKewanee, Illinois  61443
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Proctor HospitalPeoria, Illinois  61614
Perry Memorial HospitalPrinceton, Illinois  61356
Mecosta County Medical CenterBig Rapids, Michigan  49307
Creighton University Medical CenterOmaha, Nebraska  68131-2197
Eureka HospitalEureka, Illinois  61530
Mercy HospitalCoon Rapids, Minnesota  55433
Graham Hospital AssociationCanton, Illinois  61520
Holy Family Medical CenterDes Plaines, Illinois  60016
Saint Joseph Medical CenterJoliet, Illinois  60435
Pekin HospitalPekin, Illinois  61554
Medical Oncology and Hematology AssociatesDes Moines, Iowa  50309
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Fairview-Southdale HospitalEdina, Minnesota  55435
Abbott-Northwestern HospitalMinneapolis, Minnesota  55407
Regions HospitalSaint Paul, Minnesota  55101
Saint Francis Regional Medical CenterShakopee, Minnesota  55379
Rice Memorial HospitalWillmar, Minnesota  56201
Altru Cancer CenterGrand Forks, North Dakota  58206
Geisinger Medical GroupState College, Pennsylvania  16801
Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Hospital District Sixth of Harper CountyAnthony, Kansas  67003
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Lawrence Memorial HospitalLawrence, Kansas  66044
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
Rutherford HospitalRutherfordton, North Carolina  28139
AnMed Health Cancer CenterAnderson, South Carolina  29621
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404
Mayo Clinic in FloridaJacksonville, Florida  32224
Metro Health HospitalGrand Rapids, Michigan  49506
University of VirginiaCharlottesville, Virginia  22908
Hennepin County Medical CenterMinneapolis, Minnesota  
Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Cancer Center of Kansas - McPhersonMcPherson, Kansas  67460
Mid Dakota ClinicBismarck, North Dakota  58501
Wichita CCOPWichita, Kansas  67214-3882
Alegent Health Immanuel Medical CenterOmaha, Nebraska  68122
Alegent Health Bergan Mercy Medical CenterOmaha, Nebraska  68124
Metro-Minnesota CCOPSt. Louis Park, Minnesota  
Lakeview HospitalStillwater, Minnesota  55082
Virginia Commonwealth UniversityRichmond, Virginia  
New Ulm Medical CenterNew Ulm, Minnesota  56073
OSF Saint Francis Medical CenterPeoria, Illinois  61637
Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Rush - Copley Medical CenterAurora, Illinois  60504
Saint Anthony Memorial HospitalEffingham, Illinois  62401
Hopedale Medical Complex - HospitalHopedale, Illinois  61747
Joliet Oncology-Hematology Associates LimitedJoliet, Illinois  60435
Community Cancer Center FoundationNormal, Illinois  61761
Illinois CancerCare-Ottawa ClinicOttawa, Illinois  61350
Ottawa Regional Hospital and Healthcare CenterOttawa, Illinois  61350
Pekin Cancer Treatment CenterPekin, Illinois  61554
Illinois Oncology Research Association CCOPPeoria, Illinois  61615
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Illinois Valley HospitalPeru, Illinois  61354
Saint Margaret's HospitalSpring Valley, Illinois  61362
Carle Clinic-Urbana MainUrbana, Illinois  61801
Saint Anthony Memorial Health CenterMichigan City, Indiana  46360
Cedar Rapids Oncology AssociationCedar Rapids, Iowa  52403
Mercy HospitalCedar Rapids, Iowa  52403
Medical Oncology and Hematology Associates-West Des MoinesClive, Iowa  50325
Iowa Oncology Research Association CCOPDes Moines, Iowa  50309
Mercy CapitolDes Moines, Iowa  50307
Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des MoinesDes Moines, Iowa  50309
Mercy Medical Center - North IowaMason City, Iowa  50401
Mercy Medical Center-Sioux CitySioux City, Iowa  51104
Saint Luke's Regional Medical CenterSioux City, Iowa  51104
Cancer Center of Kansas - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas-KingmanKingman, Kansas  67068
Cancer Center of Kansas - ParsonsParsons, Kansas  67357
Cancer Center of Kansas - PrattPratt, Kansas  67124
Cancer Center of Kansas-Wichita Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas - Main OfficeWichita, Kansas  67214
Michigan Cancer Research Consortium Community Clinical Oncology ProgramAnn Arbor, Michigan  48106
Oakwood HospitalDearborn, Michigan  48123
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Green Bay Oncology - EscanabaEscanaba, Michigan  49431
Grand Rapids Clinical Oncology ProgramGrand Rapids, Michigan  49503
Saint Mary's Health CareGrand Rapids, Michigan  49503
Spectrum Health at Butterworth CampusGrand Rapids, Michigan  49503
Green Bay Oncology - Iron MountainIron Mountain, Michigan  49801
Allegiance HealthJackson, Michigan  49201
Sparrow HospitalLansing, Michigan  48912
Saint Mary Mercy HospitalLivonia, Michigan  48154
Mercy Health Partners-Mercy CampusMuskegon, Michigan  49443
Saint Joseph Mercy OaklandPontiac, Michigan  48341-2985
Saint Joseph Mercy Port HuronPort Huron, Michigan  48060
Saint Mary's of MichiganSaginaw, Michigan  48601
Saint John Macomb-Oakland HospitalWarren, Michigan  48093
Medini, Eitan MD (UIA Investigator)Alexandria, Minnesota  56308
Miller-Dwan HospitalDuluth, Minnesota  55805
Unity HospitalFridley, Minnesota  55432
Saint John's Hospital - HealtheastMaplewood, Minnesota  55109
Minnesota Oncology Hematology PA-MaplewoodMaplewood, Minnesota  55109
North Memorial Medical Health CenterRobbinsdale, Minnesota  55422
Saint Cloud HospitalSaint Cloud, Minnesota  56303
Park Nicollet Clinic - Saint Louis ParkSaint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-WoodburyWoodbury, Minnesota  55125
Lincoln Medical Education Foundation Cancer Resource CenterLincoln, Nebraska  68510
Missouri Valley Cancer Consortium CCOPOmaha, Nebraska  68106
Saint Alexius Medical CenterBismarck, North Dakota  58501
Geisinger Wyoming ValleyWilkes-Barre, Pennsylvania  18711
Upstate Carolina CCOPSpartanburg, South Carolina  29303
Saint Vincent HospitalGreen Bay, Wisconsin  54301
Green Bay Oncology Limited at Saint Mary's HospitalGreen Bay, Wisconsin  54303
Saint Mary's HospitalGreen Bay, Wisconsin  54303
Green Bay Oncology at Saint Vincent HospitalGreen Bay, Wisconsin  54301-3526
Bay Area Medical CenterMarinette, Wisconsin  54143
Green Bay Oncology - Oconto FallsOconto Falls, Wisconsin  54154
Green Bay Oncology - Sturgeon BaySturgeon Bay, Wisconsin  54235
Roger Maris Cancer CenterFargo, North Dakota  58122
Illinois CancerCare-BloomingtonBloomington%, Illinois  61701
Illinois CancerCare-CantonCanton, Illinois  61520
Illinois CancerCare-CarthageCarthage, Illinois  62321
Illinois CancerCare-EurekaEureka, Illinois  61530
Illinois CancerCare-HavanaHavana, Illinois  62644
Illinois CancerCare-Kewanee ClinicKewanee, Illinois  61443
Illinois CancerCare-MacombMacomb, Illinois  61455
Illinois CancerCare-MonmouthMonmouth, Illinois  61462
Illinois CancerCare-Community Cancer CenterNormal, Illinois  61761
Illinois CancerCare-PekinPekin, Illinois  61603
Illinois CancerCare-PeruPeru, Illinois  61354
Illinois CancerCare-PrincetonPrinceton, Illinois  61356
Illinois CancerCare-Spring ValleySpring Valley, Illinois  61362
Cancer Center of Kansas-LiberalLiberal, Kansas  67901
Holy Family Memorial HospitalManitowoc, Wisconsin  54221
Saint Francis HospitalGreenville, South Carolina  29601
Saint Nicholas HospitalMadison, Wisconsin  53715
Alegent Health Lakeside HospitalOmaha, Nebraska  68130
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
Carle Foundation - Carle Cancer CenterUrbana, Illinois  61801
Oncology Associates at Mercy Medical CenterCedar Rapids, Iowa  52403
Sanford Clinic North-FargoFargo, North Dakota  58102
Sanford Medical Center-FargoFargo, North Dakota  58122
North Central Cancer Treatment GroupRochester, Minnesota  55905
Sanford Clinic North-BemidgiBemidji, Minnesota  56601
Essentia Health Duluth Clinic CCOPDuluth, Minnesota  55805
Essentia Health Saint Mary's Medical CenterDuluth, Minnesota  55805
Sanford Bismarck Medical CenterBismarck, North Dakota  58501
Geisinger Medical Center-Cancer Center HazeltonHazleton, Pennsylvania  18201
Illinois CancerCare GalesburgGalesburg, Illinois  61401
Bronson Battle CreekBattle Creek, Michigan  49017