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

Phase 1

Terminated

• Conditions: Glioblastoma
• Interventions: Drug: Phase 1 Dose Escalation; Drug: Phase 1b; Drug: Ancillary Study

• Registration Number: NCT01499251
• Lead Sponsor: Actelion

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 The study will end when all patients (excluding those prematurely withdrawn or lost to follow-up) in each part of the study have completed a visit at month 12 and 30 days of safety follow-up.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-12-20
• Study First Submitted QC: 2011-12-22
• Study First Posted: 2011-12-26
• Study Start: 2012-01
• Primary Completion: 2016-01
• Study Completion: 2016-04
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-04
• Last Update Posted: 2016-05-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Macitentan	Phase 1 Dose Escalation	Macitentan in combination with dose-dense temozolomide
Macitentan	Phase 1b	Macitentan in combination with dose-dense temozolomide
Macitentan	Ancillary Study	Macitentan in combination with dose-dense temozolomide

Primary Outcome Measures

Name	Time	Method
To determine the maximum tolerated dose of macitentan in combination with dose-dense temozolomide	Phase I Dose Escalation period (Dose-Limiting Toxicity from Baseline to 28 days for each dose level)

Secondary Outcome Measures

Name	Time	Method
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.	for all study periods
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.	for all study periods
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.	for all study periods
Number of patients with treatment-emergent ECG abnormalities	Up to 30 days after discontinuation of macitentan	for all study periods
Change from baseline in vital signs	Up to 30 days after discontinuation of macitentan	for all study periods: systolic and diastolic blood pressure \[supine and standing\], average of the two measurements and pulse rate.
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.	for all study periods

Trial Locations

Locations (1)

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States