Glioblastoma Multiforme, Gliosarcoma
Conditions
Keywords
glioblastoma multiforme, gliosarcoma, malignant glioma, glioma, Gliadel, carmustine wafers, Avastin, bevacizumab, Temodar, temozolomide, Pro00025180, Desjardins, Duke, Preston Robert Tisch Brain Tumor Center
Brief summary
The purpose of this study is to determine the safety and effectiveness of Gliadel wafers at the time of surgery, followed by the combination of radiation, Temodar, and Avastin, and then the combination of Avastin and Temodar, after radiation is complete, on malignant brain tumors. About six weeks after surgery, subjects will begin standard radiation therapy, a fixed dose of Avastin every 2 weeks, and daily Temodar for the six and a half weeks of radiation. Beginning 2-3 weeks after the last radiation therapy, subjects will be given the same fixed dose of Avastin intravenously (through the vein) every 14 days. They will also be given a higher dose of oral Temodar to take daily the first 5 days of each 28-day study cycle.
Interventions
DRUGGliadel
Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection.
RADIATIONRadiation Therapy
At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy.
DRUGAvastin
Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively. Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days.
DRUGTemodar
At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation. In addition, beginning 2-3 weeks after the last radiation therapy, but not greater than 8 weeks, patients will be treated with 5 day Temodar (200 mg/ m2).
Sponsors
Genentech, Inc.
Eisai Inc.
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have a MRI consistent with a WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma), and be candidates for surgical resection with Gliadel wafer placement. Patients have to be within 6 weeks of the last major surgical procedure. * Age ≥ 18 years * Candidates for Gliadel * If a prior procedure was done, an interval of at least 2 weeks and not \> 8 weeks between prior major surgical procedure and study enrollment * No prior radiotherapy or chemotherapy for a brain tumor * Karnofsky \> 60% * Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 cells/microliters, platelets ≥ 125,000 cells/microliters * Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of normal. * Signed informed consent approved by the Institutional Review Board * If sexually active, patients must agree to use appropriate contraceptive measures for the duration of the study and for 6 months afterwards as stated in the informed consent.
Exclusion criteria
* Pregnancy or breast feeding. * Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids. * Active infection requiring IV antibiotics. * Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor. * Evidence of \> grade 1 CNS hemorrhage on baseline MRI or CT scan. * Prior treatment with Avastin for any condition * Prior, unrelated malignancy requiring active treatment with the exception cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin Avastin-Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 21-month Overall Survival | 21 months | The percentage of participants alive at 21 months after the start of study treatment. Overall survival was calculated from the date study treatment started until the date of death or the date of last follow-up if alive. Kaplan-Meier methods were used to estimate overall survival. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | 21 months | Overall survival was defined as the time in months from the start of SRS to the date of death or last contact if alive. Kaplan-Meier methods were used to estimate overall survival. |
| Median Progression-free Survival | 21 months | Progression-free survival was defined as the time in months from the date study treatment started until the date of progression or the date of death if death occurred before progression, or until the date of last follow-up if alive without progression. Kaplan-Meier methods were used to estimate progression-free survival. |
| Unacceptable Toxicity Related to the Treatment Regimen | 27 months | The number of patients experiencing unacceptable toxicity defined as the occurrence of ≥ grade 2 CNS hemorrhage or treatment-related grade 4 or 5 non-hematologic toxicity. |
Countries
United States
Participant flow
Recruitment details
Study recruitment was stopped early due to unacceptable toxicity after 41 participants were enrolled.
Pre-assignment details
Forty-seven subjects were consented to the study. Six subjects were screen failures and were not enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Gliadel, Radiation Therapy, Avastin, Temodar Single arm study where patients with newly diagnosed Grade IV malignant glioma will receive Gliadel at the time of resection, followed by radiation therapy (XRT), Avastin, and Temodar for approximately 6 1/2 weeks, followed by Avastin and Temodar post-radiation Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy. Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively. Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation. | 41 |
| Total | 41 |
Baseline characteristics
| Characteristic | Gliadel, Radiation Therapy, Avastin, Temodar |
|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 41 |
| serious Total, serious adverse events | 18 / 41 |
Outcome results
Primary
21-month Overall Survival
The percentage of participants alive at 21 months after the start of study treatment. Overall survival was calculated from the date study treatment started until the date of death or the date of last follow-up if alive. Kaplan-Meier methods were used to estimate overall survival.
Time frame: 21 months
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gliadel, Radiation Therapy, Avastin, Temodar | 21-month Overall Survival | 40.9 percentage of participants |
Secondary
Median Overall Survival
Overall survival was defined as the time in months from the start of SRS to the date of death or last contact if alive. Kaplan-Meier methods were used to estimate overall survival.
Time frame: 21 months
Population: Intent-to-treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gliadel, Radiation Therapy, Avastin, Temodar | Median Overall Survival | 19.4 months |
Secondary
Median Progression-free Survival
Progression-free survival was defined as the time in months from the date study treatment started until the date of progression or the date of death if death occurred before progression, or until the date of last follow-up if alive without progression. Kaplan-Meier methods were used to estimate progression-free survival.
Time frame: 21 months
Population: Intent-to-treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gliadel, Radiation Therapy, Avastin, Temodar | Median Progression-free Survival | 11.3 months |
Secondary
Unacceptable Toxicity Related to the Treatment Regimen
The number of patients experiencing unacceptable toxicity defined as the occurrence of ≥ grade 2 CNS hemorrhage or treatment-related grade 4 or 5 non-hematologic toxicity.
Time frame: 27 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gliadel, Radiation Therapy, Avastin, Temodar | Unacceptable Toxicity Related to the Treatment Regimen | 6.0 Participants |