Overview
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.
Principal investigator
Eligibility criteria
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 exclusion criteria are not eligible for study participation:
* MRI defining progression is consistent with a diagnosis of glioblastoma or radiation necrosis.
* Patients who are considered to be refractory to EBRT and temozolomide but who have not progressed.
* Prior systemic therapy for recurrence of AA.
* Presence of extracranial or leptomeningeal disease.
* Prior lomustine use.
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the patient unsuitable for the study.
* Pregnant or breastfeeding.
* 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 exclusion criteria are not eligible for study participation:
* MRI defining progression is consistent with a diagnosis of glioblastoma or radiation necrosis.
* Patients who are considered to be refractory to EBRT and temozolomide but who have not progressed.
* Prior systemic therapy for recurrence of AA.
* Presence of extracranial or leptomeningeal disease.
* Prior lomustine use.
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the patient unsuitable for the study.
* Pregnant or breastfeeding.
For Referring Providers
Do you have a patient you think would be a good candidate for this trial? Learn more about enrolling your patient.