AzTrials
AzTrials

Brain and Central Nervous System TumorsPhase 1/2NCT00553150

Everolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma

A Phase 1/2 study testing everolimus, temozolomide and radiation in people with Brain and Central Nervous System Tumors, run by Alliance for Clinical Trials in Oncology at 178 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain and Central Nervous System Tumors
What is being tested?
everolimus, temozolomide and radiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
122 participants
Where
178 sitesUnited States
Study dates
Mar 2009to 15 Nov 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Must be willing to have imaging scans submitted for central review
  • Ability to understand and willingness to sign a written informed consent
  • At least 1 week, but no more than 6 weeks since prior surgical resection or biopsy
  • Must comply with antibiotic prophylaxis with either trimethoprim/sulfamethoxazole (daily or 3 times per week), oral dapsone (daily) combined with daily levofloxacin, or monthly pentamidine (inhaled or IV) combined with daily levofloxacin

Who cannot join

  • 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
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  • 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
  • Severe allergy to sulfa medications
  • Inability to tolerate levofloxacin with dapsone or pentamidine (inhaled or IV)
  • PRIOR CONCURRENT THERAPY:
  • Prior chemotherapy for any brain tumor
  • Prior temozolomide or mTOR inhibitor therapies
  • Any prior cranial radiotherapy
  • Planned immunization with attenuated live vaccines ≤ 7 days prior to and during study period
  • At least 21 days since prior major surgery (excluding neurosurgical biopsy, resection of brain tumor, or treatment of immediate post-neurosurgical complication [e.g., intracranial hematoma])
  • Concurrent or prior treatment for this cancer with any other investigational agents
  • Concurrent enzyme-inducing anticonvulsants (EIACs) or other strong inducers of CYP3A4 (i.e., carbamazepine, phenytoin, phenobarbital/primidone, rifabutin, rifampin, or St. John's wort)
  • Concurrent therapeutic doses of warfarin
  • Low molecular weight heparin is allowed
  • Concurrent systematic leukocyte growth factors (e.g., G-CSF or GM-CSF), except for the treatment of severe neutropenia
  • Concurrent drugs or substances known to inhibit or induce CYP3A
  • Other concurrent chronic treatment with immunosuppressive agents except dexamethasone
  • Other concurrent anticancer agents
  • Concurrent live vaccines

Trial locations and contacts

178 sites in 1 country.

178 sites in 1 country

United States178 sites

  • Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest

    Allentown, Pennsylvania, 18105

  • McFarland Clinic, PC

    Ames, Iowa, 50010

  • Saint Joseph Mercy Cancer Center

    Ann Arbor, Michigan, 48106-0995

  • CCOP - Michigan Cancer Research Consortium

    Ann Arbor, Michigan, 48106

  • St. Francis Hospital and Health Centers - Beech Grove Campus

    Beech Grove, Indiana, 46107

  • MeritCare Bemidji

    Bemidji, Minnesota, 56601

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Study site

    Bettendorf, Iowa, 52722

  • CCOP - Montana Cancer Consortium

    Billings, Montana, 59101

  • St. Vincent Healthcare Cancer Care Services

    Billings, Montana, 59101

  • Hematology-Oncology Centers of the Northern Rockies - Billings

    Billings, Montana, 59102

  • Billings Clinic - Downtown

    Billings, Montana, 59107-7000

  • Illinois CancerCare - Bloomington

    Bloomington, Illinois, 61701

  • St. Joseph Medical Center

    Bloomington, Illinois, 61701

  • Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center

    Boise, Idaho, 83706

  • Bozeman Deaconess Cancer Center

    Bozeman, Montana, 59715

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • St. James Healthcare Cancer Care

    Butte, Montana, 59701

  • Graham Hospital

    Canton, Illinois, 61520

  • Illinois CancerCare - Canton

    Canton, Illinois, 61520

  • Illinois CancerCare - Carthage

    Carthage, Illinois, 62321

  • Memorial Hospital

    Carthage, Illinois, 62321

  • Cedar Rapids Oncology Associates

    Cedar Rapids, Iowa, 52403

  • Mercy Regional Cancer Center at Mercy Medical Center

    Cedar Rapids, Iowa, 52403

  • Cancer Center of Kansas, PA - Chanute

    Chanute, Kansas, 66720

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Charles M. Barrett Cancer Center at University Hospital

    Cincinnati, Ohio, 45267

  • Riverside Methodist Hospital Cancer Care

    Columbus, Ohio, 43214-3998

  • CCOP - Columbus

    Columbus, Ohio, 43215

  • Grant Medical Center Cancer Care

    Columbus, Ohio, 43215

  • Mount Carmel Health - West Hospital

    Columbus, Ohio, 43222

  • Doctors Hospital at Ohio Health

    Columbus, Ohio, 43228

  • Mercy and Unity Cancer Center at Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Grandview Hospital

    Dayton, Ohio, 45405

  • Good Samaritan Hospital

    Dayton, Ohio, 45406

  • David L. Rike Cancer Center at Miami Valley Hospital

    Dayton, Ohio, 45409

  • Samaritan North Cancer Care Center

    Dayton, Ohio, 45415

  • CCOP - Dayton

    Dayton, Ohio, 45420

  • Oakwood Cancer Center at Oakwood Hospital and Medical Center

    Dearborn, Michigan, 48123-2500

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Cancer Center of Kansas, PA - Dodge City

    Dodge City, Kansas, 67801

  • Duluth Clinic Cancer Center - Duluth

    Duluth, Minnesota, 55805-1983

  • CCOP - Duluth

    Duluth, Minnesota, 55805

  • Miller - Dwan Medical Center

    Duluth, Minnesota, 55805

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Cancer Center of Kansas, PA - El Dorado

    El Dorado, Kansas, 67042

  • Green Bay Oncology, Limited - Escanaba

    Escanaba, Michigan, 49431

  • Eureka Community Hospital

    Eureka, Illinois, 61530

  • Illinois CancerCare - Eureka

    Eureka, Illinois, 61530

  • MeritCare Broadway

    Fargo, North Dakota, 58102

  • CCOP - MeritCare Hospital

    Fargo, North Dakota, 58122

  • Roger Maris Cancer Center at MeritCare Hospital

    Fargo, North Dakota, 58122

  • Blanchard Valley Medical Associates

    Findlay, Ohio, 45840

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Cancer Center of Kansas - Fort Scott

    Fort Scott, Kansas, 66701

  • Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Mercy and Unity Cancer Center at Unity Hospital

    Fridley, Minnesota, 55432

  • Galesburg Clinic, PC

    Galesburg, Illinois, 61401

  • Illinois CancerCare - Galesburg

    Galesburg, Illinois, 61401

  • Genesys Regional Medical Center

    Grand Blanc, Michigan, 48439

  • Altru Cancer Center at Altru Hospital

    Grand Forks, North Dakota, 58201

  • Great Falls Clinic - Main Facility

    Great Falls, Montana, 59405

  • Sletten Cancer Institute at Benefis Healthcare

    Great Falls, Montana, 59405

  • Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center

    Green Bay, Wisconsin, 54301-3526

  • Green Bay Oncology, Limited at St. Mary's Hospital

    Green Bay, Wisconsin, 54303

  • St. Mary's Hospital Medical Center - Green Bay

    Green Bay, Wisconsin, 54303

  • St. Vincent Hospital Regional Cancer Center

    Green Bay, Wisconsin, 54307-3508

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Van Elslander Cancer Center at St. John Hospital and Medical Center

    Grosse Pointe Woods, Michigan, 48236

  • Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

    Hartford, Connecticut, 06105

  • Illinois CancerCare - Havana

    Havana, Illinois, 62644

  • Mason District Hospital

    Havana, Illinois, 62644

  • Northern Montana Hospital

    Havre, Montana, 59501

  • St. Peter's Hospital

    Helena, Montana, 59601

  • Hutchinson Area Health Care

    Hutchinson, Minnesota, 55350

  • Cancer Center of Kansas-Independence

    Independence, Kansas, 67301

  • Dickinson County Healthcare System

    Iron Mountain, Michigan, 49801

  • Foote Memorial Hospital

    Jackson, Michigan, 49201

  • Mayo Clinic - Jacksonville

    Jacksonville, Florida, 32224

  • Glacier Oncology, PLLC

    Kalispell, Montana, 59901

  • Kalispell Medical Oncology at KRMC

    Kalispell, Montana, 59901

  • Kalispell Regional Medical Center

    Kalispell, Montana, 59901

  • Charles F. Kettering Memorial Hospital

    Kettering, Ohio, 45429

  • Illinois CancerCare - Kewanee Clinic

    Kewanee, Illinois, 61443

  • Cancer Center of Kansas, PA - Kingman

    Kingman, Kansas, 67068

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

  • Sparrow Regional Cancer Center

    Lansing, Michigan, 48912-1811

  • Lawrence Memorial Hospital

    Lawrence, Kansas, 66044

  • Cancer Center of Kansas, PA - Liberal

    Liberal, Kansas, 67901

  • Cancer Resource Center - Lincoln

    Lincoln, Nebraska, 68510

  • St. Mary Mercy Hospital

    Livonia, Michigan, 48154

  • Illinois CancerCare - Macomb

    Macomb, Illinois, 61455

  • McDonough District Hospital

    Macomb, Illinois, 61455

  • HealthEast Cancer Care at St. John's Hospital

    Maplewood, Minnesota, 55109

  • Minnesota Oncology - Maplewood

    Maplewood, Minnesota, 55109

  • Strecker Cancer Center at Marietta Memorial Hospital

    Marietta, Ohio, 45750

  • Bay Area Cancer Care Center at Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • Cancer Center of Kansas, PA - McPherson

    McPherson, Kansas, 67460

  • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center - Minneapolis

    Minneapolis, Minnesota, 55415

  • Montana Cancer Specialists at Montana Cancer Center

    Missoula, Montana, 59807-7877

  • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

    Missoula, Montana, 59807

  • Trinity Cancer Center at Trinity Medical Center - 7th Street Campus

    Moline, Illinois, 61265

  • Study site

    Moline, Illinois, 61265

  • Illinois CancerCare - Monmouth

    Monmouth, Illinois, 61462

  • OSF Holy Family Medical Center

    Monmouth, Illinois, 61462

  • Knox Community Hospital

    Mount Vernon, Ohio, 43050

  • New Ulm Medical Center

    New Ulm, Minnesota, 56073

  • Licking Memorial Cancer Care Program at Licking Memorial Hospital

    Newark, Ohio, 43055

  • Cancer Center of Kansas, PA - Newton

    Newton, Kansas, 67114

  • BroMenn Regional Medical Center

    Normal, Illinois, 61761

  • Community Cancer Center

    Normal, Illinois, 61761

  • Illinois CancerCare - Community Cancer Center

    Normal, Illinois, 61761

  • Green Bay Oncology, Limited - Oconto Falls

    Oconto Falls, Wisconsin, 54154

  • CCOP - Missouri Valley Cancer Consortium

    Omaha, Nebraska, 68106

  • Immanuel Medical Center

    Omaha, Nebraska, 68122

  • Alegant Health Cancer Center at Bergan Mercy Medical Center

    Omaha, Nebraska, 68124

  • Lakeside Hospital

    Omaha, Nebraska, 68130

  • Creighton University Medical Center

    Omaha, Nebraska, 68131-2197

  • Community Hospital of Ottawa

    Ottawa, Illinois, 61350

  • Oncology Hematology Associates of Central Illinois, PC - Ottawa

    Ottawa, Illinois, 61350

  • Cancer Center of Kansas, PA - Parsons

    Parsons, Kansas, 67357

  • Cancer Treatment Center at Pekin Hospital

    Pekin, Illinois, 61554

  • Illinois CancerCare - Pekin

    Pekin, Illinois, 61603

  • CCOP - Illinois Oncology Research Association

    Peoria, Illinois, 61615

  • Oncology Hematology Associates of Central Illinois, PC - Peoria

    Peoria, Illinois, 61615

  • Methodist Medical Center of Illinois

    Peoria, Illinois, 61636

  • OSF St. Francis Medical Center

    Peoria, Illinois, 61637

  • Illinois CancerCare - Peru

    Peru, Illinois, 61354

  • Illinois Valley Community Hospital

    Peru, Illinois, 61354

  • St. Joseph Mercy Oakland

    Pontiac, Michigan, 48341-2985

  • Mercy Regional Cancer Center at Mercy Hospital

    Port Huron, Michigan, 48060

  • Cancer Center of Kansas, PA - Pratt

    Pratt, Kansas, 67124

  • Illinois CancerCare - Princeton

    Princeton, Illinois, 61356

  • Perry Memorial Hospital

    Princeton, Illinois, 61356

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57701

  • Reid Hospital & Health Care Services

    Richmond, Indiana, 47374

  • Humphrey Cancer Center at North Memorial Outpatient Center

    Robbinsdale, Minnesota, 55422-2900

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Mercy Clinic Cancer and Hematology - Rolla

    Rolla, Missouri, 65401

  • Seton Cancer Institute at Saint Mary's - Saginaw

    Saginaw, Michigan, 48601

  • CCOP - Metro-Minnesota

    Saint Louis Park, Minnesota, 55416

  • Park Nicollet Cancer Center

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital Cancer Care Center

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Cancer Center of Kansas, PA - Salina

    Salina, Kansas, 67401

  • Mayo Clinic Scottsdale

    Scottsdale, Arizona, 85259-5499

  • St. Francis Cancer Center at St. Francis Medical Center

    Shakopee, Minnesota, 55379

  • Welch Cancer Center at Sheridan Memorial Hospital

    Sheridan, Wyoming, 82801

  • Siouxland Hematology-Oncology Associates, LLP

    Sioux City, Iowa, 51101

  • Mercy Medical Center - Sioux City

    Sioux City, Iowa, 51102

  • St. Luke's Regional Medical Center

    Sioux City, Iowa, 51104

  • Medical X-Ray Center, PC

    Sioux Falls, South Dakota, 57105

  • Sanford Cancer Center at Sanford USD Medical Center

    Sioux Falls, South Dakota, 57117-5039

  • Illinois CancerCare - Spring Valley

    Spring Valley, Illinois, 61362

  • CCOP - Cancer Research for the Ozarks

    Springfield, Missouri, 65802

  • St. John's Regional Health Center

    Springfield, Missouri, 65804

  • Hulston Cancer Center at Cox Medical Center South

    Springfield, Missouri, 65807

  • Community Hospital of Springfield and Clark County

    Springfield, Ohio, 45505

  • Lakeview Hospital

    Stillwater, Minnesota, 55082

  • Green Bay Oncology, Limited - Sturgeon Bay

    Sturgeon Bay, Wisconsin, 54235

  • UVMC Cancer Care Center at Upper Valley Medical Center

    Troy, Ohio, 45373-1300

  • Ridgeview Medical Center

    Waconia, Minnesota, 55387

  • St. John Macomb Hospital

    Warren, Michigan, 48093

  • Cancer Center of Kansas, PA - Wellington

    Wellington, Kansas, 67152

  • Precision Radiotherapy at University Pointe

    West Chester, Ohio, 45069

  • Mount Carmel St. Ann's Cancer Center

    Westerville, Ohio, 43081

  • Associates in Womens Health, PA - North Review

    Wichita, Kansas, 67208

  • Cancer Center of Kansas, PA - Wichita

    Wichita, Kansas, 67214

  • CCOP - Wichita

    Wichita, Kansas, 67214

  • Via Christi Cancer Center at Via Christi Regional Medical Center

    Wichita, Kansas, 67214

  • Wesley Medical Center

    Wichita, Kansas, 67214

  • Willmar Cancer Center at Rice Memorial Hospital

    Willmar, Minnesota, 56201

  • Cancer Center of Kansas, PA - Winfield

    Winfield, Kansas, 67156

  • Minnesota Oncology - Woodbury

    Woodbury, Minnesota, 55125

  • Ruth G. McMillan Cancer Center at Greene Memorial Hospital

    Xenia, Ohio, 45385

  • Genesis - Good Samaritan Hospital

    Zanesville, Ohio, 43701

Other trials in United States

About this study

Official title: Phase I/II Evaluation of Everolimus (RAD001), Radiation and Temozolomide (TMZ) Followed by Adjuvant Temozolomide and Everolimus in Newly Diagnosed Glioblastoma

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.

Read the detailed description

OBJECTIVES:

  • To determine the maximum tolerated dose (MTD) of everolimus in combination with temozolomide and 3D-conformal radiotherapy or intensity-modulated radiotherapy (IMRT) followed by adjuvant temozolomide with or without everolimus in patients with newly diagnosed glioblastoma. (Mayo Clinic Rochester [MCR] AND Mayo Clinic Jacksonville [MCJ] patients only) (Phase I)
  • To assess and describe the adverse events of everolimus in combination with temozolomide and 3D-conformal radiotherapy or IMRT followed by adjuvant temozolomide with or without everolimus in patients with newly diagnosed glioblastoma. (MCR and MCJ patients only) (Phase I)
  • To assess treatment effectiveness of everolimus in combination with temozolomide and 3D-conformal radiotherapy or IMRT followed by adjuvant temozolomide with or without everolimus, until progression, in patients with newly diagnosed glioblastoma. (all North Central Cancer Treatment Group [NCCTG] patients) (Phase II)
  • To characterize the toxicities of everolimus in combination with temozolomide and 3D-conformal radiotherapy or IMRT followed by adjuvant temozolomide with or without everolimus in patients with newly diagnosed glioblastoma. (all NCCTG patients) (Phase II)
  • Evaluate whether suppression of fludeoxyglucose F18 (18FDG) uptake in tumor and normal brain can be used to determine a biologically effective dose for efficient penetration of everolimus through the blood-brain barrier. (MCR and MCJ patients only) (Phase I)
  • Correlate everolimus levels with 18FDG uptake suppression in tumor and normal brain. (MCR and MCJ patients only) (Phase I)
  • Assess the relationship between efficacy endpoints (i.e., survival, progression-free survival, and response) and changes in 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) uptake for patients treated at MCR. (all NCCTG patients) (Phase II)
  • Assess the relationship between efficacy endpoints (i.e., survival, progression-free survival, and response), and phospho-Akt, PTEN status, and MGMT expression and promoter methylation status. (all NCCTG patients) (Phase II)
  • Assess the relationship between efficacy endpoints (i.e., survival, progression-free survival, and response) and baseline gene expression signatures from paraffin embedded pre-treatment tumor samples. (all NCCTG patients) (Phase II)
  • Correlate gene expression between paraffin and frozen samples. (all NCCTG patients) (Phase II)
  • Evaluate potential mechanisms of therapy resistance in recurrent tumor samples obtained at the time of surgery for recurrent disease. (Phase I and II)

OUTLINE: This is a multicenter, phase I dose-escalation study of everolimus followed by a phase II study.

  • Phase I (Mayo Clinic Rochester [MCR] AND Mayo Clinic Jacksonville [MCJ] ONLY):
  • Concurrent therapy (courses 1 and 2): Patients receive oral everolimus once weekly in weeks 1-7 or 1-8 and oral temozolomide once daily in weeks 2-7 or 3-8. Patients also undergo radiotherapy 5 days a week in either weeks 2-7 or 3-8. Four to six weeks later, patients proceed to adjuvant therapy. This rest period is defined as course 2.
  • Adjuvant therapy with everolimus and temozolomide (courses 3-8): Patients receive oral everolimus on days 1, 8, 15, and 22 and oral temozolomide on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
  • Adjuvant therapy with everolimus alone (courses 9 and all subsequent courses): Patients receive oral everolimus on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression our unacceptable toxicity.
  • Phase II (Open to MCR center ONLY) (All North Central Cancer Treatment Group [NCCTG] centers closed to accrual as of 02/17/11):
  • Concurrent therapy (courses 1 and 2): Patients 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.

Patients undergo blood sample collection periodically for pharmacological studies. Samples are analyzed for everolimus blood levels and correlated with 18FDG uptake suppression in tumor and normal brain via LC-MSMS. Previously collected tumor tissue are analyzed for protein biomarkers including PTEN gene expression levels via fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) and phosphorylation on Ser473 and Ser308 of Akt and MGMT expression and promoter methylation via IHC. Samples are also analyzed for DNA sequencing. Some samples are banked for future studies.

After completion of study treatment, patients are followed every 2 months for 1 year, every 3 months for 1 year, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 138 patients (24 patients in phase I and 114 patients in phase II) will be accrued for this study.

Keywords
adult gliosarcoma, adult giant cell glioblastoma, adult glioblastoma, adult anaplastic astrocytoma, adult diffuse astrocytoma, adult pilocytic astrocytoma, adult subependymal giant cell astrocytoma
Medical subject headings
Central Nervous System Neoplasms, Gliosarcoma, Glioblastoma, Astrocytoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00553150
Study groupRoleWhat they receive
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.
Receives: Drug: everolimus; Drug: temozolomide; Radiation: radiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 49 days

  2. 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".

    Measured: at 12 months

Secondary outcomes (4)

  1. Response Rate, as Measured in Patients Receiving FLT-PET Imaging (Phase II)

    The response rate is defined as the percentage of patients receiving F-fluorothymidine positron emission tomography (FLT-PET) imaging whose cancer shrinks or disappears after treatment. A reduction in standardized uptake value (SUV) of 30% or greater in the T1-post-gadolinium scan volume of interest (T1-gad VOI) or the total tumor VOI will be considered a responsive tumor.

    Measured: Up to 5 years

  2. Time to Progression (Phase II)

    Time-to-disease progression is defined as the time from start of study therapy to documentation of disease progression. Patients who die without documentation of progression will be considered to have had tumor progression at the time of death unless there is documented evidence that no progression occurred before death. Patients who fail to return for evaluation after beginning therapy will be censored for progression on the last day of therapy. Patients who experience major treatment violations will be censored for progression on the date of treatment violation occurred. The time-to-progression distribution will be estimated using the Kaplan-Meier method. Progression is defined as at least a 25% increase in product of perpendicular diameters of contrast enhancement or mass or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians or appearance of new lesions.

    Measured: Up to 5 years

  3. Progression-free-survival at 6 Months (Phase II)

    Progression-free-survival at 6 months: is the proportion of patients alive and progression-free at 6 months after start of regimen. This proportion will be estimated using the binomial point estimator and the binomial 95% confidence interval estimated. Progression is defined as at least a 25% increase in product of perpendicular diameters of contrast enhancement or mass or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians or appearance of new lesions.

    Measured: at 6 months

  4. Overall Survival Time

    Overall survival: The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier method.

    Measured: Up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2007 (estimated)
  2. Study startMar 2009
  3. Primary completionJan 2012
  4. Study completion15 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
122 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00553150
Sponsor's protocol ID
NCCTG-N057K
Other IDs
NCI-2009-00654, CDR0000573917
Status last verified
Feb 2020
First submitted
2 Nov 2007
Last updated
13 Feb 2020
Data monitoring committee
No

Publications

  • 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.

  • Sarkaria 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.

    PubMed 20864273

  • Sarkaria 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing everolimus, temozolomide and radiation in people with Brain and Central Nervous System Tumors, run by Alliance for Clinical Trials in Oncology at 178 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 178 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: Up to 49 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00553150, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2020.

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