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

Study Overview
=================
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.

Official Title
-----------------
A Randomized Phase 3 Open-Label Study To Evaluate the Efficacy and Safety of Eflornithine With Lomustine Compared to Lomustine Alone in Patients With AA That Progress/Recur After Irradiation and Adjuvant Temozolomide Chemotherapy

Conditions
-----------------
Anaplastic Astrocytoma, Recurrent Anaplastic Astrocytoma

Intervention / Treatment
-----------------
* Drug: Eflornithine
* Drug: Lomustine
* Drug: Lomustine


Participation Criteria
=================
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: Gd-contrast lesion margins are not clearly defined, Gd-contrast lesions are only measurable in one dimension, Gd-contrast lesion has two perpendicular diameters less than 10 mm, Gd-contrast lesion has two perpendicular diameters greater than 10 mm but less than 20 mm and lesion does not demonstrate central necrosis, 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eflornithine + Lomustine<br>Eflornithine dosed on a 2 weeks on, 1 week off schedule + Lomustine dosed every 6 weeks | Drug: Eflornithine<br>* Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 week on, 1 week off schedule<br>* Other names: DFMO;Drug: Lomustine<br>* Lomustine 90 mg/m2 administered orally once every 6 weeks<br>* Other names: Gleostine;|
| Active Comparator: Lomustine<br>Lomustine dosed every 6 weeks | Drug: Lomustine<br>* Lomustine 110 mg/m2 administered orally once every 6 weeks<br>* Other names: Gleostine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | 4 years | 
| Objective response rate (ORR) |  | 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Progressive Brain Tumor, 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, Recurrent Brain Tumor