Abstract CT136: STELLAR: 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
Authors: Levin Victor A. , Cruickshank Scott 
Published: July 2017

Abstract
Background: Eflornithine, a novel cytostatic agent, irreversibly inhibits ornithine decarboxylase, the enzyme that catalyzes the first step in the biosynthesis of putrescine that, in conjunction with, spermidine and spermine, constitute the major polyamines of mammalian cells. More than 390 patients with high-grade gliomas have been treated with eflornithine alone or in combination with a nitrosourea or PCV (procarbazine, lomustine, and vincristine) in prior US clinical trials. In a Phase 3 randomized study of adjuvant PCV compared to PCV plus eflornithine in a total of 228 evaluable patients with anaplastic glioma (AG), overall survival (OS) was improved from a median of 61.1 months for patients on PCV to 75.8 months for patients on PCV plus eflornithine (Levin, et al., 2003).
The objective of the STELLAR study (NCT02796261) is to evaluate the efficacy and safety of eflornithine with lomustine vs. lomustine in patients with anaplastic astrocytoma (AA; WHO Grade 3 glioma) who progressed/recurred after surgery, irradiation and adjuvant temozolomide chemotherapy.
Methods: To be eligible for STELLAR, patients must have histologically proven AA with unequivocal evidence of first AA tumor progression or recurrence ≤ 3 months prior to randomization following surgical resection or biopsy, irradiation and temozolomide chemotherapy. Radiation therapy must have been completed ≥ 6 months prior to randomization and KPS &gt; 70 is required. Approximately 280 patients will be randomized 1:1 and stratified per age (≤ 45 yrs vs &gt; 45 yrs), US vs Ex-US, IDH1 status (wild type vs mutant), and number of prior surgeries (biopsy only vs 1 or 2 surgical resections). Patients will receive either eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 week on, 1 week off schedule, and lomustine 110 mg/m2 administered orally once every 6 weeks, or lomustine alone dosed at 110 mg/m2 administered orally once every 6 weeks. In both arms, lomustine will be limited to a maximum of 6 cycles or 12 months of therapy. in the combination arm, eflornithine therapy can be given up to 24 months. Radiologic tumor assessment will be performed per institutional standard of care. The primary endpoint will be overall survival (OS). Secondary objectives include progression free survival (PFS) and objective response rate (ORR). The study sample size was calculated by assuming true median OS of 12 months for the treatment arm receiving lomustine monotherapy. It is hypothesized true median OS will be at least 18 months for the eflornithine plus lomustine arm. Under the assumption that OS follows an exponential probability distribution for each treatment arm, such an improvement represents a true hazard ratio of 0.667 (investigational arm/control arm). Inferential comparisons of OS will be performed using a stratified log-rank test, stratifying on the randomization stratification factors. Total accrual of approximately 274 patients (137 per treatment arm), and total information of 194 deaths is estimated to provide 80% power to detect a 33% reduction in the OS failure hazard rate. The STELLAR study is currently enrolling patients in the US, Germany and Italy and is anticipated to remain open for enrollment through the first half of 2018.
Citation Format: Victor A. Levin, Scott Cruickshank. STELLAR: 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 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT136. doi:10.1158/1538-7445.AM2017-CT136