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

Actelion Pharmaceuticals

Status and phase

Terminated

Phase 1

Conditions

Glioblastoma

Treatments

Drug: Macitentan in combination with RT and TMZ

Study type

Interventional

Funder types

Industry

Identifiers

NCT02254954

AC-055-118

Details and patient eligibility

About

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.

Enrollment

30 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.