A Phase 1/1b, Open-label Study in Patients With Recurrent Glioblastoma to Assess the Safety and Tolerability of Macitentan in Combination With Dose-dense Temozolomide
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Enrollment
- 75
- Locations
- 1
- Primary Endpoint
- To determine the maximum tolerated dose of macitentan in combination with dose-dense temozolomide
Study Overview
Brief Summary
This is an open-label, single arm, Phase 1 study to assess the safety and tolerability of macitentan in combination with dose-dense temozolomide in adult patients with recurrent glioblastoma or gliosarcoma. The study is composed of three parts. A Phase 1 Dose Escalation Period with a traditional 3+3 design will determine the maximum tolerated dose of macitentan in combination with dose-dense temozolomide. A Phase 1b Period will expand the safety and tolerability data of two doses of macitentan and dose-dense temozolomide selected from the Dose Escalation Period and explore efficacy. An Ancillary Study will further evaluate the effects of macitentan on biomarkers in brain tumor tissue.
The study is planned to have a minimum duration of 12 months. The study will end when all patients (excluding those prematurely withdrawn or lost to follow-up) in each part of the study have completed a visit at month 12 and 30 days of safety follow-up.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Macitentan
Macitentan in combination with dose-dense temozolomide
Intervention: Phase 1 Dose Escalation (Drug)
Macitentan
Macitentan in combination with dose-dense temozolomide
Intervention: Phase 1b (Drug)
Macitentan
Macitentan in combination with dose-dense temozolomide
Intervention: Ancillary Study (Drug)
Outcomes
Primary Outcomes
To determine the maximum tolerated dose of macitentan in combination with dose-dense temozolomide
Time Frame: Phase I Dose Escalation period (Dose-Limiting Toxicity from Baseline to 28 days for each dose level)
Secondary Outcomes
- Number of patients with treatment-emergent adverse events (AEs) and serious AEs(Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.)
- Incidence of treatment-emergent* marked laboratory abnormalities(Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.)
- Occurrence of at least grade 2 ALT and/or AST elevation(Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.)
- Number of patients with treatment-emergent ECG abnormalities(Up to 30 days after discontinuation of macitentan)
- Change from baseline in vital signs(Up to 30 days after discontinuation of macitentan)
- Number of patients with AEs leading to premature discontinuation of study treatment(Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.)