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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00553150
First received: November 2, 2007
Last updated: July 18, 2012
Last verified: July 2012
  Purpose

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
Genetic: fluorescence in situ hybridization
Genetic: gene expression analysis
Genetic: nucleic acid sequencing
Other: diagnostic laboratory biomarker analysis
Other: fluorine F 18 fluorothymidine
Other: immunohistochemistry staining method
Other: liquid chromatography
Other: mass spectrometry
Other: pharmacological study
Procedure: adjuvant therapy
Radiation: 3-dimensional conformal radiation therapy
Radiation: fludeoxyglucose F 18
Radiation: intensity-modulated radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: 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 National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD of everolimus in combination with temozolomide and 3D-conformal radiotherapy or intensity-modulated radiotherapy (IMRT) followed by adjuvant temozolomide with or without everolimus (Phase I) [ Designated as safety issue: Yes ]
  • Percent change in the standard uptake value (SUV) levels calculated for the identified volumes of interest (VOIs) for the FDG PET scans from baseline to after 2 doses of everolimus therapy (Phase I) [ Designated as safety issue: No ]
  • Survival at 52 weeks (Phase II) [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate (Phase II) [ Designated as safety issue: No ]
  • Time to progression (Phase II) [ Designated as safety issue: No ]
  • Overall survival (Phase II) [ Designated as safety issue: No ]
  • Progression-free-survival at 6 months (Phase II) [ Designated as safety issue: No ]
  • Adverse events [ Designated as safety issue: Yes ]
  • Distributions of laboratory variables (phospho-Akt, PTEN status, MGMT expression and promoter methylation status) [ Designated as safety issue: No ]

Estimated Enrollment: 138
Study Start Date: March 2009
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

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

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

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)

PRIOR CONCURRENT THERAPY:

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
North Central Cancer Treatment Group
Investigators
Study Chair: Jann N. Sarkaria, MD Mayo Clinic
Investigator: Evanthia Galanis, MD Mayo Clinic
Investigator: David Schiff, MD University of Virginia
Investigator: Paul D. Brown, MD Mayo Clinic
Investigator: Timothy Kaufmann, MD Mayo Clinic
Investigator: Bradley J. Erickson, MD, PhD Mayo Clinic
Investigator: Caterina Giannini, MD, PhD Mayo Clinic
Investigator: Patrick J. Peller, MD Mayo Clinic
Investigator: Steven McGraw, MD Medical X-Ray Center, PC
  More Information

Additional Information:
Publications:
Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00553150     History of Changes
Other Study ID Numbers: CDR0000573917, NCCTG-N057K
Study First Received: November 2, 2007
Last Updated: July 18, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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
Glioblastoma
Nervous System Neoplasms
Astrocytoma
Glioma
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
Everolimus
Fluorodeoxyglucose F18
Sirolimus
Temozolomide
Alkylating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Diagnostic Uses of Chemicals
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 25, 2014