Protocol Summary

Protocol No.: OCR15154

Sponsor Protocol No.: OT-15-001

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

Principal Investigator(s)
Ghiaseddin, Ashley

Objective
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.

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 280 patients will be randomized in a 1:1 ratio to receive either eflornithine + lomustine or lomustine alone.

Phase: Phase III

Age Group: Adult

Scope: National

Treatment
Eflornithine + Lomustine
Eflornithine dosed on a 2 weeks on, 1 week off schedule + Lomustine dosed every 6 weeks

Lomustine
Lomustine dosed every 6 weeks

Detailed Eligibility
INCLUSION CRITERIA:
1. Ages 18 years and older.
2. Surgical or biopsy-proven diagnosis of WHO grade 3 AA.
3. Unequivocal evidence of first AA tumor progression or recurrence ≤ 3 months prior to randomization based on MRI criteria for tumor progression using enlarging Gd-contrast enhancement and/or T2 hypersensitivity (Appendix 4). Patients with non-measurable Gd contrast enhancing tumors will only be eligible if there is no necrosis seen on MRI and/or histopathological confirmation of AA per standard of care procedures is obtained within 4 weeks prior to randomization.
4. First tumor progression or recurrence following surgical resection or biopsy, if resection is not feasible, EBRT and temozolomide chemotherapy.
5. Completion of EBRT ≥ 6 months prior to randomization.
6. 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, b) post-surgical MRI demonstrates measurable tumor on T2/FLAIR, and c) MRI performed after surgery is within 4 weeks prior to randomization.
7. Karnofsky Performance Status (KPS) score of > 70.

EXCLUSION CRITERIA:
1. MRI defining progression is consistent with a diagnosis of glioblastoma or radiation necrosis.
2. Patients who are considered to be refractory to EBRT and temozolomide but who have not progressed.
3. Prior systemic therapy for recurrence of AA.
4. Presence of extracranial or leptomeningeal disease.
5. Prior lomustine use.
6. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the patient unsuitable for the study.
7. Pregnant or breastfeeding.

Applicable Disease Sites
Brain and Nervous System

Participating Institutions
UF Gainesville : Sonisha Warren

Contact
Sonisha Warren, PhD
Phone: +1 352-294-8737

Email: sonisha.warren@neurosurgery.ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02796261