Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts 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 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Eflornithine + Lomustine
Eflornithine dosed on a 2 weeks on, 1 week off schedule + Lomustine dosed every 6 weeks
  • Drug: Eflornithine
    Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 week on, 1 week off schedule
    Other names:
    • DFMO
  • Drug: Lomustine
    Lomustine 90 mg/m2 administered orally once every 6 weeks
    Other names:
    • CCNU
    • CeeNU
    • Gleostine
Active Comparator
Lomustine
Lomustine dosed every 6 weeks
  • Drug: Eflornithine
    Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 week on, 1 week off schedule
    Other names:
    • DFMO
  • Drug: Lomustine
    Lomustine 90 mg/m2 administered orally once every 6 weeks
    Other names:
    • CCNU
    • CeeNU
    • Gleostine
  • Drug: Lomustine
    Lomustine 110 mg/m2 administered orally once every 6 weeks
    Other names:
    • CCNU
    • CeeNU
    • Gleostine

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35401
Contact:
Burt Nabors, MD
205-934-1813
bnabors@uab.edu

More Details

NCT ID
NCT02796261
Status
Recruiting
Sponsor
Orbus Therapeutics, Inc.

Study Contact

Marietta Franco, MS
6504506634
marietta.franco@orbustherapeutics.com

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 24 months.

A total of approximately 340 patients will be randomized in a 1:1 ratio to receive either eflornithine + lomustine or lomustine alone.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.