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

NCT02254954 | Terminated Phase 1

• 1 other identifier: AC-055-118
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioblastoma

Keywords

glioblastoma

Outcome Measures

Primary Outcomes (1)

• Number of subjects with dose-limiting toxicities observed during the first 10 weeks of study treatment (i.e., 6 weeks of concurrent therapy with macitentan, RT and TMZ and 4 weeks of monotherapy with macitentan).

  Start of treatment to week 10

Secondary Outcomes (10)

• Plasma concentrations of endothelin-1

  Baseline, Weeks 2, 6, and 10

• Plasma concentrations of macitentan and its metabolite

  Baseline, Weeks 2 and 6

• Area under the plasma concentration-time curve (AUCτ) for macitentan during one dosing interval for subjects treated with doses of macitentan 150 mg or higher

  Week 4

• Peak plasma concentration (Cmax) of macitentan during one dosing interval for subjects treated with doses of macitentan 150 mg or higher

  Week 4

• Time to reach peak plasma concentration (Tmax) of macitentan during one dosing interval for subjects treated with doses of macitentan 150 mg or higher

  Week 4

Study Arms (1)

Macitentan in combination with RT & TMZ

EXPERIMENTAL

Escalating doses of macitentan in combination with RT and TMZ, and maintenance TMZ.

Drug: Macitentan in combination with RT and TMZ

Interventions

Macitentan in combination with RT and TMZ DRUG

Escalating doses of macitentan in combination with RT and TMZ, and maintenance TMZ.

Also known as: Temodar (temozolomide [TMZ]), macitentan, Radiotherapy

Macitentan in combination with RT & TMZ

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• Investigational Site Web Address

MeSH Terms

Conditions

Glioblastoma

Interventions

macitentan; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2014
• First Posted: October 2, 2014
• Study Start: January 8, 2015
• Primary Completion: September 29, 2016
• Study Completion: September 29, 2016
• Last Updated: February 27, 2018

Record last verified: 2018-02

Locations

US (1)