Glioblastoma Multiforme
Conditions
Keywords
Brain Tumors, Glioblastoma Multiforme, GBM
Brief summary
To obtain preliminary data in a randomized phase II study whether PPX/RT improves progression-free survival as compared to temozolomide/RT for patients with GBM without MGMT methylation.
Detailed description
To evaluate the toxicities of PPX/RT To evaluate neuro-cognitive functional assessments of patients with GBM receiving PPX/RT To obtain preliminary data in a randomized phase II study whether PPX/RT improves overall survival as compared to temozolomide /RT for patients with GBM without MGMT methylation to facilitate planning a phase III study.
Interventions
DRUGPPX (CT2103)
XRT: 60 Gy at 2 Gy/fraction x 30 fractions PPX: 50 mg/m2/week x 6 weeks during radiation Temozolomide maintenance: Beginning 4 weeks after completion of chemoradiation, temozolomide d1-5 of 28 day cycle for 12 cycle maximum.
DRUGTemozolomide
XRT: 60 Gy at 2 Gy/fraction x 30 fractions Temozolomide, 75 mg/m2/day, 7 days per week, from the first to the last day of radiotherapy Temozolomide maintenance: Beginning 4 weeks after completion of chemoradiation, temozolomide d1-5 of 28 day cycle for 12 cycle maximum
Sponsors
Rhode Island Hospital
Milton S. Hershey Medical Center
University of Washington
University of Massachusetts, Worcester
MaineHealth
University of California, San Diego
Thomas Jefferson University
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV) * GBM must have unmethylated MGMT as determined by central laboratory * Diagnosis of GBM must be made by biopsy or surgical excision, either partial or complete; as long as there is sufficient tissue to determine MGMT status * No prior chemotherapy or radiation for brain tumor * Must be able to tolerate brain MRIs. \*A diagnostic contrast-enhanced MRI must be performed postoperatively within 42 days prior to study registration. * KPS \>60. * Age \> 18 * Life expectancy of at least 3 months. * Absolute neutrophil count \> 1500/mm3, Platelets \> 100,000/mm, * Creatinine \< 2 x ULN * ALT or AST \< 3 x upper limit of normal (ULN) and total bilirubin \< 1.5x ULN. * Patients with a prior history of low grade glioma who did not receive prior radiation or chemotherapy with transformation to grade IV brain tumor are eligible. * Women must be non-lactating, and surgically sterile, post-menopausal or have a negative serum pregnancy test and agree to use adequate birth control. Males must agree to use adequate birth control. * Voluntary, signed informed consent.
Exclusion criteria
* Acute infection or other medical condition that would impair study treatment * No other active invasive malignancy unless disease free for at least 3 years. * Prior temozolomide or PPX. * Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted. * Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields. * No diffuse leptomeningeal disease, or gliomatosis cerebri. * Use of any other experimental chemotherapy drug within the 60 days prior to randomization and during the trial. (Use of a non-chemotherapy investigational agent must be approved by the Brown University Oncology Group)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival PPX/RT Versus TMZ/RT for Patients With GBM Without Methylation | Q 3 months on study then Q3 months in f/u for yr 1, q 4 months yr 2, q 6 months for approximately 4 ys. | MRI response evaluated by RANO criteria * Complete Response (CR): Circumstance when the enhancing tumor is no longer seen by neuroimaging, with the patient off all steroids or on adrenal maintenance only; CR will be coded only if confirmed by a second CT/MR scan performed a minimum of 4 weeks after the initial scan coding a response. * Partial Response (PR): Decrease of \> 50% in the product of two diameters. Patients should be receiving stable or decreasing doses of steroids. PR will be coded only if confirmed by a second CT/MR scan performed a minimum of 4 weeks after the initial scan. * Progression (P): A \> 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. This will not need a confirmatory scan. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of XRT. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiation Plus PPX(CT2103 Radiation therapy, Monday through Friday, for 6 weeks for a total of 30 treatments
\+ intravenous PPX every week x 6 weeks for a total of 6 treatments
PPX (CT2103): XRT: 60 Gy at 2 Gy/fraction x 30 fractions PPX: 50 mg/m2/week x 6 weeks during radiation Temozolomide maintenance: Beginning 4 weeks after completion of chemoradiation, temozolomide d1-5 of 28 day cycle for 12 cycle maximum. | 42 |
| Radiation + Temozolomide Radiation therapy, Monday through Friday, for 6 weeks for a total of 30 treatments
\+ Daily oral temozolomide(TMZ) (7 days) x 6 wks for a total of 42 days
Temozolomide: XRT: 60 Gy at 2 Gy/fraction x 30 fractions Temozolomide, 75 mg/m2/day, 7 days per week, from the first to the last day of radiotherapy Temozolomide maintenance: Beginning 4 weeks after completion of chemoradiation, temozolomide d1-5 of 28 day cycle for 12 cycle maximum | 21 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Radiation + Temozolomide | Radiation Plus PPX(CT2103 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 15 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 27 Participants | 42 Participants |
| Age, Continuous | 62 years | 62 years | 62 years |
| Region of Enrollment United States | 21 participants | 42 participants | 63 participants |
| Sex: Female, Male Female | 9 Participants | 15 Participants | 24 Participants |
| Sex: Female, Male Male | 12 Participants | 27 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 41 | 18 / 18 |
| serious Total, serious adverse events | 13 / 41 | 7 / 18 |
Outcome results
Primary
Progression Free Survival PPX/RT Versus TMZ/RT for Patients With GBM Without Methylation
MRI response evaluated by RANO criteria * Complete Response (CR): Circumstance when the enhancing tumor is no longer seen by neuroimaging, with the patient off all steroids or on adrenal maintenance only; CR will be coded only if confirmed by a second CT/MR scan performed a minimum of 4 weeks after the initial scan coding a response. * Partial Response (PR): Decrease of \> 50% in the product of two diameters. Patients should be receiving stable or decreasing doses of steroids. PR will be coded only if confirmed by a second CT/MR scan performed a minimum of 4 weeks after the initial scan. * Progression (P): A \> 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. This will not need a confirmatory scan. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of XRT.
Time frame: Q 3 months on study then Q3 months in f/u for yr 1, q 4 months yr 2, q 6 months for approximately 4 ys.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiation Plus PPX(CT2103 | Progression Free Survival PPX/RT Versus TMZ/RT for Patients With GBM Without Methylation | 31 participants |
| Radiation + Temozolomide | Progression Free Survival PPX/RT Versus TMZ/RT for Patients With GBM Without Methylation | 15 participants |