Phase 2
N=122
Everolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma
Brain and Central Nervous System Tumors
Bottom Line
View on ClinicalTrials.gov: NCT00553150 ↗Enrolled (actual)
122
Serious AEs
31.1%
Results posted
Jan 2017
Primary outcome: Primary: 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) — 1; 1; 1 participants who developed DLTs
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- everolimus (Drug); temozolomide (Drug); radiation (Radiation)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Alliance for Clinical Trials in Oncology
- Primary completion
- Jan 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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) |
1; 1; 1 | — |
| PRIMARY Overall Survival at 12 Months (Phase II) |
0.64 | — |
| SECONDARY Response Rate, as Measured in Patients Receiving FLT-PET Imaging (Phase II) |
44.4 | — |
| SECONDARY Time to Progression (Phase II) |
6.4 | — |
| SECONDARY Progression-free-survival at 6 Months (Phase II) |
0.52 | — |
| SECONDARY Overall Survival Time |
15.8 | — |
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.
Eligibility 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 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
Data sourced from ClinicalTrials.gov (NCT00553150). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.