Overview

Clinical Study on Macitentan, RT and TMZ Concurrent Therapy Followed by Maintenance Macitentan and TMZ in Newly Diagnosed Glioblastoma

Status:
Terminated
Trial end date:
2016-09-29
Target enrollment:
0
Participant gender:
All
Summary
This is a prospective, single-center, open-label, 3+3 dose escalation Phase 1 safety study. Adults with newly diagnosed GBM or gliosarcoma will receive macitentan in addition to the standard of care treatment for GBM. The study consists of a screening period, a treatment period, and a 30-day safety follow up period. The treatment period includes 6 weeks of concurrent therapy (macitentan+RT+TMZ), 4 weeks of monotherapy (macitentan) and 12 cycles of maintenance therapy (macitentan+TMZ). The study will end when the last treated subject has completed study treatment and the 30-day safety follow-up period. The planned duration of the study is approximately 34-38 months depending on the number of dose levels and cohorts of subjects enrolled. Subject participation in the study will be for approximately 16 months.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Actelion
Treatments:
Macitentan
Temozolomide
Criteria
Inclusion Criteria:

- Subjects at least 18 years of age

- Histologically proven supratentorial GBM or gliosarcoma

- Use of effective contraception by women of childbearing potental.

- Use of effective contraception by fertile males with a female partner of childbearing
potential.

- Interval of at least 3 weeks after biopsy or open surgery and able to begin study
treatment.

- Result from a post-operative contrast-enhanced brain MRI within 72 hours after surgery
or biopsy.

- Adequate bone marrow function

- Karnofsky Performance Score of at least 70.

Exclusion Criteria:

- Prior treatment for glioblastoma or gliosarcoma.

- Evidence of leptomeningeal spread of glibolastoma or gliosarcoma.

- Tumor foci below the tentorium or beyond the cranial vault.

- Evidence of recent hemorrhage on post-operative contrast enhanced brain MRI (except
hemosiderin, resolving hemorrhage changes related to surgery, presence of punctuate
hemorrhage in tumor).

- Aspartate aminotransferase or alanine aminotransferase > 3 times the upper limit of
normal.

- Supine systolic blood pressure < 100 mmHg or diastolic blood pressure < 50 mmHg.

- Medical history of orthostatic hypotension.

- International normalized ratio > 1.5 on anticoagulant therapy, active bleeding on low
molecular weight heparin, or chronic condition with a high risk of bleeding.

- Severe renal impairment.

- Severe hepatic impairment.

- Severe, active co-morbidity: (e.g. cardiac disease; respiratory disease; chronic
hepatitis; hemtological and bone marrow diseases; severe malabsoprtion; human
immunodeficiency virus).

- No concurrent strong CYP3A4 inducers or inhibitors.

- No investigational drug within 4 weeks of starting study treatment.

- Any life-threatening condition that could affect protocol compliance.