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

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
First received: November 2, 2007
Last updated: July 9, 2015
Last verified: July 2015

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.

Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: everolimus
Drug: temozolomide
Radiation: radiation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Evaluation of Everolimus (RAD001), Radiation and Temozolomide (TMZ) Followed by Adjuvant Temozolomide and Everolimus in Newly Diagnosed Glioblastoma

Resource links provided by NLM:

Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Survival at 52 weeks (Phase II) [ Time Frame: at 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Time to progression (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Progression-free-survival at 6 months (Phase II) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]

Enrollment: 117
Study Start Date: March 2009
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus (RAD001), Radiation (RT), Temozolomide (TMZ)

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.

Drug: everolimus Drug: temozolomide Radiation: radiation

  Show Detailed Description


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Histologically confirmed diagnosis of 1 of the following:

    • Glioblastoma multiforme (grade 4 astrocytoma)
    • Other grade 4 astrocytoma variants (e.g., giant cell)

      • No grade 4 oligodendrogliomas or oligoastrocytomas
    • Gliosarcoma
  • Newly diagnosed disease
  • Measurable disease ≥ 1 cm³ (phase I patients only)
  • Some patients may be registered on protocol NCCTG-947252
  • No oligodendrogliomas or oligoastrocytomas


Inclusion criteria:

  • 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
  • Must be willing to have imaging scans submitted for central review
  • Ability to understand and willingness to sign a written informed consent

Exclusion criteria:

  • 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
  • Severe allergy to sulfa medications
  • Inability to tolerate levofloxacin with dapsone or pentamidine (inhaled or IV)


Inclusion criteria:

  • 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

Exclusion criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00553150

  Show 178 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Jann N. Sarkaria, MD Mayo Clinic
  More Information

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, 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.

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00553150     History of Changes
Other Study ID Numbers: NCCTG-N057K  NCI-2009-00654  CDR0000573917 
Study First Received: November 2, 2007
Last Updated: July 9, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
adult gliosarcoma
adult giant cell glioblastoma
adult glioblastoma
adult anaplastic astrocytoma
adult diffuse astrocytoma
adult pilocytic astrocytoma
adult subependymal giant cell astrocytoma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Alkylating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 24, 2016