Everolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma
Phase I/II Evaluation of Everolimus (RAD001), Radiation and Temozolomide (TMZ) Followed by Adjuvant Temozolomide and Everolimus in Newly Diagnosed Glioblastoma
3 other identifiers
interventional
122
1 country
178
Brief Summary
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking some of the blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving everolimus together with temozolomide and radiation therapy may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2009
Longer than P75 for phase_1
178 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 2, 2007
CompletedFirst Posted
Study publicly available on registry
November 5, 2007
CompletedStudy Start
First participant enrolled
March 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2012
CompletedResults Posted
Study results publicly available
January 11, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
November 15, 2019
CompletedFebruary 13, 2020
February 1, 2020
2.8 years
November 2, 2007
November 14, 2016
February 4, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Maximum Tolerated Dose (MTD) of Everolimus (RAD001) in Combination With Temozolomide (TMZ) and 3D-conformal Radiotherapy (RT) or Intensity-modulated Radiotherapy (IMRT) Followed by Adjuvant TMZ With or Without RAD001 (Phase I)
Patients were assessed during RT for dose-limiting toxicities (DLT), which were defined as failure to deliver greater than 75% of the planned doses of TMZ or RAD001 during RT, interruption of RT for more than 5 days because of toxicity, or the following: \>= Grade 3 diarrhea or skin rash; \>= Grade 4 neutropenia, leukopenia, or thrombocytopenia; \>= Grade 4 hypertriglyceridemia, hypercholesterolemia, or hyperglycemia despite optimal medial management, other \>= 3 non-hematologic events; or \>= Grade 4 radiation dermatitis. Maximum tolerated dose (MTD) was defined a priori as the highest dose level at which 0 or 1 of 6 patients developed DLTs. The number of patients who developed DLTs are reported here by dose level, with the MTD reported in the statistical analysis section.
Up to 49 days
Overall Survival at 12 Months (Phase II)
The primary endpoint is overall survival at 12 months (OS12) after entry into this study. The proportion of successes will be estimated using the binomial point estimator (number of successes divided by the total number of evaluable patients) and the binomial 95% confidence interval estimated. A patient who is evaluable and survive more than 12 months (i.e. 365 days or more) after start of therapy will be classified as a "success". Patients who die within 12 months after start of therapy will be considered to have "failed".
at 12 months
Secondary Outcomes (4)
Response Rate, as Measured in Patients Receiving FLT-PET Imaging (Phase II)
Up to 5 years
Time to Progression (Phase II)
Up to 5 years
Progression-free-survival at 6 Months (Phase II)
at 6 months
Overall Survival Time
Up to 15 years
Study Arms (1)
Everolimus (RAD001), Radiation (RT), Temozolomide (TMZ)
EXPERIMENTALPatients receive oral everolimus and oral temozolomide and 3D-conformal radiotherapy or IMRT as in phase I. Patients will undergo a 4-6 week rest period in course 2 and then proceed to adjuvant therapy. Adjuvant therapy with everolimus and temozolomide (courses 3-8): Patients receive oral everolimus and oral temozolomide as in phase I. Adjuvant therapy with everolimus alone (courses 9 and all subsequent courses): Patients receive oral everolimus as in phase I. All patients undergo fludeoxyglucose (FDG)- or fluorothymidine-labeled PET/CT scans at baseline and periodically during treatment.
Interventions
Eligibility Criteria
You may qualify if:
- ECOG performance status 0-2
- ANC ≥ 1,500/μL
- Hemoglobin ≥ 9.0 g/dL
- Platelet count ≥ 100,000/μL
- Total bilirubin ≤ 2.5 x institutional upper limit of normal (ULN)
- Serum total cholesterol \< 350 mg/dL
- Serum total triglycerides \< 400 mg/dL
- AST ≤ 2.5 x ULN
- Creatinine ≤ 1.5 x ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 60 days after completion of study therapy
- Must be willing to undergo 2 mandatory research PET or PET/CT scans (all MCR and MCJ patients in phase I and MCR only patients in phase II)
- Must be willing to abstain from eating or drinking grapefruit or grapefruit juice during study treatment
- Must be willing to follow a diet low in fat and cholesterol while taking everolimus
- +2 more criteria
You may not qualify if:
- Other active cancers requiring therapy to control disease or prior cancer diagnoses which pose a greater than 30% risk of death within the next 2 years
- Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active uncontrolled peptic ulcer disease
- Uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing, uncontrolled, or active (acute or chronic) infection or disorder
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study requirements
- Severely impaired lung function
- Uncontrolled diabetes (fasting serum glucose \> 2 x ULN) OR diabetes that would interfere with the performance of the FDG-PET/CT or FDG-PET scans
- Liver disease (e.g., cirrhosis, chronic active hepatitis, chronic persistent hepatitis, or history of hepatitis B)
- Known HIV positivity
- Positive hepatitis B antigen (HBsAg) or hepatitis C serology (HCV) tests
- Any history of allergy or intolerance to dacarbazine (DTIC)
- Significant traumatic injury within the past 21 days
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (178)
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259-5499, United States
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
Hartford, Connecticut, 06105, United States
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224, United States
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
Boise, Idaho, 83706, United States
Illinois CancerCare - Bloomington
Bloomington, Illinois, 61701, United States
St. Joseph Medical Center
Bloomington, Illinois, 61701, United States
Graham Hospital
Canton, Illinois, 61520, United States
Illinois CancerCare - Canton
Canton, Illinois, 61520, United States
Illinois CancerCare - Carthage
Carthage, Illinois, 62321, United States
Memorial Hospital
Carthage, Illinois, 62321, United States
Eureka Community Hospital
Eureka, Illinois, 61530, United States
Illinois CancerCare - Eureka
Eureka, Illinois, 61530, United States
Galesburg Clinic, PC
Galesburg, Illinois, 61401, United States
Illinois CancerCare - Galesburg
Galesburg, Illinois, 61401, United States
Illinois CancerCare - Havana
Havana, Illinois, 62644, United States
Mason District Hospital
Havana, Illinois, 62644, United States
Illinois CancerCare - Kewanee Clinic
Kewanee, Illinois, 61443, United States
Illinois CancerCare - Macomb
Macomb, Illinois, 61455, United States
McDonough District Hospital
Macomb, Illinois, 61455, United States
Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
Moline, Illinois, 61265, United States
Unknown Facility
Moline, Illinois, 61265, United States
Illinois CancerCare - Monmouth
Monmouth, Illinois, 61462, United States
OSF Holy Family Medical Center
Monmouth, Illinois, 61462, United States
BroMenn Regional Medical Center
Normal, Illinois, 61761, United States
Community Cancer Center
Normal, Illinois, 61761, United States
Illinois CancerCare - Community Cancer Center
Normal, Illinois, 61761, United States
Community Hospital of Ottawa
Ottawa, Illinois, 61350, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa
Ottawa, Illinois, 61350, United States
Cancer Treatment Center at Pekin Hospital
Pekin, Illinois, 61554, United States
Illinois CancerCare - Pekin
Pekin, Illinois, 61603, United States
CCOP - Illinois Oncology Research Association
Peoria, Illinois, 61615, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
Peoria, Illinois, 61615, United States
Methodist Medical Center of Illinois
Peoria, Illinois, 61636, United States
OSF St. Francis Medical Center
Peoria, Illinois, 61637, United States
Illinois CancerCare - Peru
Peru, Illinois, 61354, United States
Illinois Valley Community Hospital
Peru, Illinois, 61354, United States
Illinois CancerCare - Princeton
Princeton, Illinois, 61356, United States
Perry Memorial Hospital
Princeton, Illinois, 61356, United States
Illinois CancerCare - Spring Valley
Spring Valley, Illinois, 61362, United States
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, 46107, United States
Reid Hospital & Health Care Services
Richmond, Indiana, 47374, United States
McFarland Clinic, PC
Ames, Iowa, 50010, United States
Unknown Facility
Bettendorf, Iowa, 52722, United States
Cedar Rapids Oncology Associates
Cedar Rapids, Iowa, 52403, United States
Mercy Regional Cancer Center at Mercy Medical Center
Cedar Rapids, Iowa, 52403, United States
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, 51101, United States
Mercy Medical Center - Sioux City
Sioux City, Iowa, 51102, United States
St. Luke's Regional Medical Center
Sioux City, Iowa, 51104, United States
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, 66720, United States
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, 67801, United States
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, 67042, United States
Cancer Center of Kansas - Fort Scott
Fort Scott, Kansas, 66701, United States
Cancer Center of Kansas-Independence
Independence, Kansas, 67301, United States
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, 67068, United States
Lawrence Memorial Hospital
Lawrence, Kansas, 66044, United States
Cancer Center of Kansas, PA - Liberal
Liberal, Kansas, 67901, United States
Cancer Center of Kansas, PA - McPherson
McPherson, Kansas, 67460, United States
Cancer Center of Kansas, PA - Newton
Newton, Kansas, 67114, United States
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, 67357, United States
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, 67124, United States
Cancer Center of Kansas, PA - Salina
Salina, Kansas, 67401, United States
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, 67152, United States
Associates in Womens Health, PA - North Review
Wichita, Kansas, 67208, United States
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, 67214, United States
CCOP - Wichita
Wichita, Kansas, 67214, United States
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, 67214, United States
Wesley Medical Center
Wichita, Kansas, 67214, United States
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, 67156, United States
Saint Joseph Mercy Cancer Center
Ann Arbor, Michigan, 48106-0995, United States
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, 48106, United States
Oakwood Cancer Center at Oakwood Hospital and Medical Center
Dearborn, Michigan, 48123-2500, United States
Green Bay Oncology, Limited - Escanaba
Escanaba, Michigan, 49431, United States
Genesys Hurley Cancer Institute
Flint, Michigan, 48503, United States
Hurley Medical Center
Flint, Michigan, 48503, United States
Genesys Regional Medical Center
Grand Blanc, Michigan, 48439, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, 48236, United States
Dickinson County Healthcare System
Iron Mountain, Michigan, 49801, United States
Foote Memorial Hospital
Jackson, Michigan, 49201, United States
Sparrow Regional Cancer Center
Lansing, Michigan, 48912-1811, United States
St. Mary Mercy Hospital
Livonia, Michigan, 48154, United States
St. Joseph Mercy Oakland
Pontiac, Michigan, 48341-2985, United States
Mercy Regional Cancer Center at Mercy Hospital
Port Huron, Michigan, 48060, United States
Seton Cancer Institute at Saint Mary's - Saginaw
Saginaw, Michigan, 48601, United States
St. John Macomb Hospital
Warren, Michigan, 48093, United States
MeritCare Bemidji
Bemidji, Minnesota, 56601, United States
Fairview Ridges Hospital
Burnsville, Minnesota, 55337, United States
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Duluth Clinic Cancer Center - Duluth
Duluth, Minnesota, 55805-1983, United States
CCOP - Duluth
Duluth, Minnesota, 55805, United States
Miller - Dwan Medical Center
Duluth, Minnesota, 55805, United States
Fairview Southdale Hospital
Edina, Minnesota, 55435, United States
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, 55432, United States
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350, United States
HealthEast Cancer Care at St. John's Hospital
Maplewood, Minnesota, 55109, United States
Minnesota Oncology - Maplewood
Maplewood, Minnesota, 55109, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Hennepin County Medical Center - Minneapolis
Minneapolis, Minnesota, 55415, United States
New Ulm Medical Center
New Ulm, Minnesota, 56073, United States
Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, 55422-2900, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905, United States
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, 55416, United States
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital Cancer Care Center
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
St. Francis Cancer Center at St. Francis Medical Center
Shakopee, Minnesota, 55379, United States
Lakeview Hospital
Stillwater, Minnesota, 55082, United States
Ridgeview Medical Center
Waconia, Minnesota, 55387, United States
Willmar Cancer Center at Rice Memorial Hospital
Willmar, Minnesota, 56201, United States
Minnesota Oncology - Woodbury
Woodbury, Minnesota, 55125, United States
Mercy Clinic Cancer and Hematology - Rolla
Rolla, Missouri, 65401, United States
CCOP - Cancer Research for the Ozarks
Springfield, Missouri, 65802, United States
St. John's Regional Health Center
Springfield, Missouri, 65804, United States
Hulston Cancer Center at Cox Medical Center South
Springfield, Missouri, 65807, United States
CCOP - Montana Cancer Consortium
Billings, Montana, 59101, United States
St. Vincent Healthcare Cancer Care Services
Billings, Montana, 59101, United States
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings, Montana, 59102, United States
Billings Clinic - Downtown
Billings, Montana, 59107-7000, United States
Bozeman Deaconess Cancer Center
Bozeman, Montana, 59715, United States
St. James Healthcare Cancer Care
Butte, Montana, 59701, United States
Great Falls Clinic - Main Facility
Great Falls, Montana, 59405, United States
Sletten Cancer Institute at Benefis Healthcare
Great Falls, Montana, 59405, United States
Northern Montana Hospital
Havre, Montana, 59501, United States
St. Peter's Hospital
Helena, Montana, 59601, United States
Glacier Oncology, PLLC
Kalispell, Montana, 59901, United States
Kalispell Medical Oncology at KRMC
Kalispell, Montana, 59901, United States
Kalispell Regional Medical Center
Kalispell, Montana, 59901, United States
Montana Cancer Specialists at Montana Cancer Center
Missoula, Montana, 59807-7877, United States
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Missoula, Montana, 59807, United States
Cancer Resource Center - Lincoln
Lincoln, Nebraska, 68510, United States
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, 68106, United States
Immanuel Medical Center
Omaha, Nebraska, 68122, United States
Alegant Health Cancer Center at Bergan Mercy Medical Center
Omaha, Nebraska, 68124, United States
Lakeside Hospital
Omaha, Nebraska, 68130, United States
Creighton University Medical Center
Omaha, Nebraska, 68131-2197, United States
MeritCare Broadway
Fargo, North Dakota, 58102, United States
CCOP - MeritCare Hospital
Fargo, North Dakota, 58122, United States
Roger Maris Cancer Center at MeritCare Hospital
Fargo, North Dakota, 58122, United States
Altru Cancer Center at Altru Hospital
Grand Forks, North Dakota, 58201, United States
Adena Regional Medical Center
Chillicothe, Ohio, 45601, United States
Charles M. Barrett Cancer Center at University Hospital
Cincinnati, Ohio, 45267, United States
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, 43214-3998, United States
CCOP - Columbus
Columbus, Ohio, 43215, United States
Grant Medical Center Cancer Care
Columbus, Ohio, 43215, United States
Mount Carmel Health - West Hospital
Columbus, Ohio, 43222, United States
Doctors Hospital at Ohio Health
Columbus, Ohio, 43228, United States
Grandview Hospital
Dayton, Ohio, 45405, United States
Good Samaritan Hospital
Dayton, Ohio, 45406, United States
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, 45409, United States
Samaritan North Cancer Care Center
Dayton, Ohio, 45415, United States
CCOP - Dayton
Dayton, Ohio, 45420, United States
Grady Memorial Hospital
Delaware, Ohio, 43015, United States
Blanchard Valley Medical Associates
Findlay, Ohio, 45840, United States
Middletown Regional Hospital
Franklin, Ohio, 45005-1066, United States
Wayne Hospital
Greenville, Ohio, 45331, United States
Charles F. Kettering Memorial Hospital
Kettering, Ohio, 45429, United States
Fairfield Medical Center
Lancaster, Ohio, 43130, United States
Strecker Cancer Center at Marietta Memorial Hospital
Marietta, Ohio, 45750, United States
Knox Community Hospital
Mount Vernon, Ohio, 43050, United States
Licking Memorial Cancer Care Program at Licking Memorial Hospital
Newark, Ohio, 43055, United States
Community Hospital of Springfield and Clark County
Springfield, Ohio, 45505, United States
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, 45373-1300, United States
Precision Radiotherapy at University Pointe
West Chester, Ohio, 45069, United States
Mount Carmel St. Ann's Cancer Center
Westerville, Ohio, 43081, United States
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, 45385, United States
Genesis - Good Samaritan Hospital
Zanesville, Ohio, 43701, United States
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
Allentown, Pennsylvania, 18105, United States
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017, United States
Rapid City Regional Hospital
Rapid City, South Dakota, 57701, United States
Medical X-Ray Center, PC
Sioux Falls, South Dakota, 57105, United States
Sanford Cancer Center at Sanford USD Medical Center
Sioux Falls, South Dakota, 57117-5039, United States
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, 54301-3526, United States
Green Bay Oncology, Limited at St. Mary's Hospital
Green Bay, Wisconsin, 54303, United States
St. Mary's Hospital Medical Center - Green Bay
Green Bay, Wisconsin, 54303, United States
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, 54307-3508, United States
Bay Area Cancer Care Center at Bay Area Medical Center
Marinette, Wisconsin, 54143, United States
Green Bay Oncology, Limited - Oconto Falls
Oconto Falls, Wisconsin, 54154, United States
Green Bay Oncology, Limited - Sturgeon Bay
Sturgeon Bay, Wisconsin, 54235, United States
Welch Cancer Center at Sheridan Memorial Hospital
Sheridan, Wyoming, 82801, United States
Related Publications (3)
Ma D, Galanis E, Schiff D, et al.: NCCTG N057K phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: A North Central Cancer Treatment Group trial. [Abstract] J Clin Oncol 30 (Suppl 15): A-2031, 2012.
RESULTSarkaria JN, Galanis E, Wu W, Peller PJ, Giannini C, Brown PD, Uhm JH, McGraw S, Jaeckle KA, Buckner JC. North Central Cancer Treatment Group Phase I trial N057K of everolimus (RAD001) and temozolomide in combination with radiation therapy in patients with newly diagnosed glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2011 Oct 1;81(2):468-75. doi: 10.1016/j.ijrobp.2010.05.064. Epub 2010 Sep 23.
PMID: 20864273RESULTSarkaria JN, Peller PJ, Galanis E, et al.: FLT-PET analysis of early response to everolimus in newly diagnosed glioblastoma patients enrolled on NCCTG N057K. [Abstract] J Clin Oncol 29 (Suppl 15): A-e12501, 2011.
RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Jann N. Sarkaria, M.D.
- Organization
- Mayo Clinic
Study Officials
- STUDY CHAIR
Jann N. Sarkaria, MD
Mayo Clinic
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 2, 2007
First Posted
November 5, 2007
Study Start
March 1, 2009
Primary Completion
January 1, 2012
Study Completion
November 15, 2019
Last Updated
February 13, 2020
Results First Posted
January 11, 2017
Record last verified: 2020-02