Everolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Status: Recruiting
Phase: Phase 1/Phase 2
Diagnosis: Brain/Neuro Cancer: Newly Diagnosed
NCT ID: NCT01062399
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID:
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor 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 and to see how well it works in treating patients with newly diagnosed glioblastoma multiforme.
Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital
Overall PI:
Brian Alexander, MD, MPH,
Brigham and Women's Hospital
Site-responsible Investigators:
Kevin OH, MD,
Massachusetts General Hospital
Contacts:
Dana-Farber Cancer Institute:
Lisa Doherty,
ldoherty1@partners.org
Massachusetts General Hospital:
Cancer Trials Call Center, 877-789-6100
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed glioblastoma multiforme (GBM) (WHO grade IV) by central
pathology review
- Gliosarcoma allowed
- Tumor must have a supratentorial component
- Diagnosis must have been made by surgical excision, either partial or complete
excision, within the past 5 weeks
- Stereotactic biopsy or Cavitron ultrasonic aspirator-derived tissue are not
allowed
- Tumor tissue available for correlative studies (phase II only)
- Patients must have ≥ 1 block of tissue; if a block cannot be submitted, two
tissue specimens punched with a skin punch (2 mm diameter) from the tissue block
containing the tumor may be submitted
- No recurrent or multifocal malignant glioma
- No metastases detected below the tentorium or beyond the cranial vault
PATIENT CHARACTERISTICS:
- Karnofsky performance status 70-100%
- ANC ≥ 1,800/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
- PT/INR ≤ 1.5
- BUN ≤ 30 mg/dL
- Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times normal
- ALT and AST ≤ 2.5 times normal
- Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤
2.5 times ULN (if one or both of these thresholds are exceeded, patients are eligible
only after initiation of appropriate lipid-lowering medication)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other invasive malignancy within the past 3 years except for nonmelanoma skin
cancer or carcinoma in situ of the breast, oral cavity, or cervix
- No severe, active co-morbidity, defined as follows:
- NYHA class III-IV symptomatic congestive heart failure
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial
infarction within the past 6 months, serious uncontrolled cardiac arrhythmia, or
any other clinically significant cardiac disease
- Severely impaired lung function, defined as spirometry and DLCO that is 50% of
the normal predicted value and/or oxygen saturation that is ≤ 88% at rest on
room air
- Uncontrolled diabetes, defined as fasting serum glucose > 1.5 times ULN
- Active (acute or chronic) or uncontrolled severe infections requiring IV
antibiotics
- Liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent
hepatitis
- AIDS based upon current Centers for Disease Control and Prevention definition or
known HIV seropositivity (HIV testing is not required for study entry)
- Active connective tissue disorders such as lupus erythematosus or scleroderma
that, in the opinion of the treating physician, may put the patient at high risk
for radiation toxicity
- Other major medical illness or psychiatric impairment that, in the
investigator's opinion, will prevent administration or completion of study
treatment
- No impaired gastrointestinal (GI) function or GI disease that may significantly alter
the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- No history of deep vein thrombosis or pulmonary embolism
- No prior allergic reaction to temozolomide
- No known hypersensitivity to mTOR inhibitors (e.g., sirolimus, temsirolimus,
everolimus) or to their excipients
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from the effects of surgery, postoperative infection, and other
complications
- No prior temozolomide
- No prior mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus)
- No prior Gliadel wafers or any other intratumoral or intracavitary treatment
- No prior radiotherapy to the head or neck (except for T1 glottic cancer) resulting in
overlap of radiotherapy fields
- No prior chemotherapy or radiosensitizers for cancer of the head and neck region
- Prior chemotherapy for a different cancer is allowed
- No prior radiotherapy or chemotherapy for GBM
- No prior or concurrent treatment on any other therapeutic clinical study
- At least 14 days since prior and no concurrent enzyme-inducing anti-epileptic drugs
- Concurrent anticoagulation allowed provided target INR ≤ 1.5 AND patient is on a
stable dose of warfarin or low molecular weight heparin for > 2 weeks