Study to Evaluate Eflornithine + Lomustine vs Lomustine in Recurrent Anaplastic Astrocytoma (AA) Patients
Study to Evaluate Eflornithine + Lomustine vs Lomustine in Recurrent Anaplastic Astrocytoma (AA) Patients
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.
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.
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.