Astrocytoma, Glioblastoma, Glioma, Oligodendroglioma
Conditions
Brief summary
The purpose of this non-randomized, open-label, multicenter, Phase II, 2-stage design, RESCUE study is to test the hypothesis that continuous 28-day oral dosing (28/28) with dose-intense temozolomide (50 mg/m\^2) for up to 12 months may overcome resistance and be effective in the management of adult patients with malignant glioma who have failed following at least 2 cycles (2 months) of conventional 5-day (5/28) cycles of high-dose temozolomide (150-200 mg/m\^2).
Interventions
DRUGTemozolomide
Subjects will receive temozolomide 50 mg/m\^2 for cycles of 28 days for 12 months or until progression
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients, greater than 18 years old. * Surgically confirmed diagnosis of malignant glioma, specifically anaplastic glioma (anaplastic astrocytoma \[AA\], anaplastic oligodendroglioma \[AO\], anaplastic oligoastrocytoma \[AOA\]) or glioblastoma multiforme (GBM). * Must have completed at least 2 cycles (2 months) of conventional 5/28 temozolomide, with radiological evidence of progression. * GBM treated with concurrent chemoradiation with temozolomide according to the EORTC/NCIC (European Organization for Research & Treatment of Cancer/National Cancer Institute of Canada) protocol. * Evidence of progression confirmed radiologically (CT \[computed tomography\] or MRI \[magnetic resonance imaging\]). * Patients must be enrolled within 2 weeks of last radiological confirmation of progression, except for patients undergoing surgical resection. * Patients undergoing surgical resection for recurrent disease must be enrolled within 2 weeks of the post-surgical scan. * Patients with no residual disease after surgery are allowed. * Steroids dose should have been stabilized during the last 2 weeks prior to enrollment. * Use of medically approved contraception in fertile males and females. * Women of childbearing potential must have a negative urine or serum pregnancy test (urinary excretion or serum level of bHCG \[beta human chorionic gonadotropin\]) within 24 hours of inclusion in the study. * Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. * Signed informed consent form.
Exclusion criteria
* GBM progression during the first 2 months of adjuvant temozolomide (5/28). * AA progression during the first 2 months of standard temozolomide therapy (5/28). * Chemotherapy for the malignant glioma other than temozolomide. * More than one prior course of chemotherapy with temozolomide. * Patient evolving from anaplastic glioma to GBM following primary therapy. * Patient older than 70 years or who received no conventional chemoradiation regimen. * Patient who received radiotherapy for recurrent disease. * Patient with metastatic disease. * Known human immunodeficiency virus (HIV) infection. * History of non-compliance to other therapies. * Inadequate hematological, renal and hepatic function according to all of the following laboratory values (to be performed within 14 days, inclusive, prior to study inclusion): * Absolute neutrophil count \<=1.5 ×10\^9/L; * Platelets \<=100 ×10\^9/L; * Hemoglobin \<90 g/L; * Serum creatinine \>=1.5 times upper limit of laboratory normal (ULN); * Total serum bilirubin \>=1.5 times ULN; * ASAT (AST \[aspartate aminotransferase\]) or ALAT (ALT \[alanine aminotransferase) \>2.0 times ULN; * Alkaline phosphatase of \>2.5 times ULN. * Known chronic hepatitis B or hepatitis C infection. * Any other serious medical condition, according to the medical judgment of the physician prior to inclusion in the study. * Any medical condition that could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction). * Other malignancies during the previous 5 years with the exception of surgically cured carcinoma in-situ of the cervix and basal cell carcinoma or non-melanoma skin cancer. * Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule as discussed with the patient before inclusion in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Surviving at Six Months of Treatment Without Evidence of Disease Progression. | 6 months | Progression-free survival as determined by Kaplan-Meier method. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Temozolomide Temozolomide will be administered at a dose of 50 mg/m\^2 for cycles of 28 days for 12 months or until progression. | 120 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not meet inclusion criteria | 4 |
| Overall Study | Disease progression | 101 |
Baseline characteristics
| Characteristic | Temozolomide |
|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 11 |
| Region of Enrollment Canada | 120 participants |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 111 / 120 |
| serious Total, serious adverse events | 27 / 120 |
Outcome results
Primary
Percentage of Participants Surviving at Six Months of Treatment Without Evidence of Disease Progression.
Progression-free survival as determined by Kaplan-Meier method.
Time frame: 6 months
Population: Participants who received allocated intervention.~The percentage of participants reported is based on the number of participants within each category (not total number of all categories combined).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Temozolomide | Percentage of Participants Surviving at Six Months of Treatment Without Evidence of Disease Progression. | Anaplastic Glioma (n=28) | 35.7 Percentage of Participants |
| Temozolomide | Percentage of Participants Surviving at Six Months of Treatment Without Evidence of Disease Progression. | Early Glioblastoma Multiforme (GBM) (n=33) | 27.3 Percentage of Participants |
| Temozolomide | Percentage of Participants Surviving at Six Months of Treatment Without Evidence of Disease Progression. | Extended Glioblastoma Multiforme (GBM) (n=27) | 7.4 Percentage of Participants |
| Temozolomide | Percentage of Participants Surviving at Six Months of Treatment Without Evidence of Disease Progression. | Rechallenge Glioblastoma Multiforme (GBM) (n=28) | 35.7 Percentage of Participants |