Clinical Study on the Safety and Tolerability of Macitentan in Combination With Dose-dense Temozolomide in Patients With Recurrent Glioblastoma

Macitentan 30, 60, 90 mg or higher in 30 mg dose increments, given orally, up to 150 mg, then 225 mg, 300 mg and 375 mg, unless otherwise decided by the Safety Monitoring Committee. Dose-dense temozolomide 150 mg/m2 body surface area alternating 1 week on 1 week off.

Macitentan given orally and daily at doses/schedule determined from the dose escalation period. Dose-dense temozolomide 150mg/m2 body surface area alternating 1 week on 1 week off.

Macitentan dosed initially for 8-14 days prior to craniotomy, then treatment interrupted from time of craniotomy until 7 days before start of dose dense temozolomide therapy. dose-dense temozolomide 150 mg/m2 body surface area alternating 1 week on 1 week off.