Anaplastic Astrocytoma, Recurrent Anaplastic Astrocytoma
Conditions
Keywords
Anaplastic Astrocytoma, Grade 3 Glioma, Glioma, Eflornithine, Brain Cancer, Brain Tumor, Neuro-oncology, Progressive Anaplastic Astrocytoma, Recurrent Anaplastic Astrocytoma, Progressive Glioma, Recurrent Glioma, Malignant Glioma, Progressive Brain Tumor, Recurrent Brain Tumor
Brief summary
The purpose of this study is to compare the efficacy and safety of eflornithine in combination with lomustine, compared to lomustine taken alone, in treating patients whose anaplastic astrocytoma has recurred/progressed after radiation and temozolomide chemotherapy.
Detailed description
This study will consist of 4 study periods of up to 50 months in total, consisting of: Screening Period - A maximum screening duration of 4 weeks. Treatment Period - Treatment Arm A up to 24 months; Treatment Arm B up to 12 months. End of Treatment Visit - A minimum of 4 weeks post last treatment for both arms. Follow-Up Period - Up to approximately 36 months, or until patient death. A total of approximately 340 patients will be randomized in a 1:1 ratio to receive either eflornithine + lomustine or lomustine alone.
Interventions
DRUGEflornithine
Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 week on, 1 week off schedule
DRUGLomustine
Lomustine 90 mg/m2 administered orally once every 6 weeks
Sponsors
Orbus Therapeutics, Inc.
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
Patients must meet all of the following inclusion criteria to be eligible for participation in this study: * Surgical or biopsy-proven diagnosis of WHO grade 3 AA. * First AA tumor progression or recurrence ≤ 6 months prior to randomization based on MRI using T2 hyperintesity, gadolinium (Gd)-contrast enhancement, or both. To avoid enrollment of patients with glioblastoma, patients with Gd-contrast enhancing tumors will be eligible if there is no necrosis seen on MRI and any of the following criteria is true: 1. Gd-contrast lesion margins are not clearly defined, 2. Gd-contrast lesions are only measurable in one dimension, 3. Gd-contrast lesion has two perpendicular diameters less than 10 mm, 4. Gd-contrast lesion has two perpendicular diameters greater than 10 mm but less than 20 mm and lesion does not demonstrate central necrosis, 5. Recent histopathological confirmation of WHO grade 3 AA * Received EBRT and temozolomide chemotherapy prior to first tumor progression or recurrence of WHO Grade 3 AA. * Completion of EBRT ≥ 6 months prior to randomization. * A patient whose AA tumor has progressed or recurred and has had another surgical resection prior to randomization will be eligible if a) pathology review confirms AA, and b) post-surgical MRI demonstrates measurable tumor on T2 FLAIR. * Karnofsky Performance Status (KPS) score of ≥ 70.
Exclusion criteria
Patients who meet any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival | 4 years |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival (PFS) | 4 years |
| Objective response rate (ORR) | 4 years |
Other
| Measure | Time frame |
|---|---|
| Pharmacokinetic Analysis - Maximum concentrations (Cmax) of eflornithine in plasma will be determined. | 1 Month |
| Clinical benefit response (CBR) based on magnetic resonance imaging (MRI) criteria | 4 years |
| PK - Area under the curve (AUC) of eflornithine in plasma will be determined. | 1 Month |
| OS rate at 18 months (OS-18) | 18 months |
| Relevance of OS, PFS, ORR, and CBR to commonly used molecular/genetic biomarkers obtained from most recent pre-study tumor samples | 4 years |
Countries
Belgium, Canada, France, Germany, Italy, Netherlands, United Kingdom, United States
Outcome results
None listed