An Open-label, Phase 1b Study to Evaluate the Safety and Tolerability of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma or Astrocytoma

Summary

The purpose of this study is to establish the recommended phase 2 dose of eflornithine in combination with temozolomide in patients whose glioblastoma or astrocytoma is newly diagnosed, and to evaluate safety and tolerability of this combination at that dose.

Detailed description

This open label dose escalation and expansion study will be conducted using a standard dose-escalation design with escalating doses of eflornithine plus temozolomide at the approved dose level, followed by an expansion cohort that will further evaluate safety and preliminary efficacy of the combination at the recommended phase 2 dose. Duration of participation will be up to approximately 104 weeks in total per patient. Screening Period - A maximum screening duration of 4 weeks. Treatment Period - Up to approximately 104 weeks. Follow-Up Visit - 4 weeks from last treatment. Long-term Survival Follow-Up - up to 2 years from last treatment. A total of up to 66 patients will be enrolled in a non-randomized fashion (patients may be added to any of the dose levels below the RP2D to a maximum of approximately 20 per dose level with the intent of further characterizing safety and pharmacokinetics).

Arms & interventions

• DrugEflornithine (Dose Level 1)

  Eflornithine 2.3 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule

• DrugEflornithine (Dose Level 2)

  Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule

• DrugEflornithine (Dose Level -1)

  Eflornithine 1.75 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule

• DrugTemozolomide

  Temozolomide 150 mg/m2 (with option to escalate per USPI maintenance phase instructions) administered orally once daily on a 5 days on, 23 days off schedule

Outcome measures

Eligibility criteria