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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02254954
Recruitment Status : Terminated (Sponsor decision due to low recruitment)
First Posted : October 2, 2014
Last Update Posted : February 27, 2018
Sponsor:
Information provided by (Responsible Party):
Actelion

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.


Condition or disease Intervention/treatment Phase
Glioblastoma Drug: Macitentan in combination with RT and TMZ Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-center, Open-label, Phase 1 Study of Macitentan, Radiotherapy and Temozolomide Concurrent Therapy Followed by Maintenance Therapy With Macitentan and Temozolomide in Subjects With Newly Diagnosed Glioblastoma
Actual Study Start Date : January 8, 2015
Actual Primary Completion Date : September 29, 2016
Actual Study Completion Date : September 29, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Macitentan

Arm Intervention/treatment
Experimental: Macitentan in combination with RT & TMZ
Escalating doses of macitentan in combination with RT and TMZ, and maintenance TMZ.
Drug: Macitentan in combination with RT and TMZ
Escalating doses of macitentan in combination with RT and TMZ, and maintenance TMZ.
Other Names:
  • Temodar (temozolomide [TMZ])
  • macitentan
  • Radiotherapy




Primary Outcome Measures :
  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). [ Time Frame: Start of treatment to week 10 ]

Secondary Outcome Measures :
  1. Plasma concentrations of endothelin-1 [ Time Frame: Baseline, Weeks 2, 6, and 10 ]
  2. Plasma concentrations of macitentan and its metabolite [ Time Frame: Baseline, Weeks 2 and 6 ]
  3. 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 [ Time Frame: Week 4 ]
  4. Peak plasma concentration (Cmax) of macitentan during one dosing interval for subjects treated with doses of macitentan 150 mg or higher [ Time Frame: Week 4 ]
  5. Time to reach peak plasma concentration (Tmax) of macitentan during one dosing interval for subjects treated with doses of macitentan 150 mg or higher [ Time Frame: Week 4 ]
  6. Number of adverse events (per Common Terminology Criteria for Adverse Events [CTCAE] criteria, version 4.03]) leading to premature discontinuation of study treatment [ Time Frame: Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days of follow-up ]
  7. Number of subjects with marked laboratory abnormalities or abnormal electrocardiogram (ECG) findings [ Time Frame: Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days of follow-up ]
  8. Change from baseline in pulse rate, systolic & diastolic blood pressure [ Time Frame: Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days follow-up ]
  9. Exploratory efficacy endpoint of proportion of subjects with progression free survival (PFS) at 6 and 12 months [ Time Frame: 6 and 12 months after the start of treatment ]
  10. Number of adverse events (per CTCAE] criteria, version 4.03]) as a measure of safety and tolerability. [ Time Frame: Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days of follow-up ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02254954


Locations
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United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Actelion
Additional Information:
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Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT02254954    
Other Study ID Numbers: AC-055-118
First Posted: October 2, 2014    Key Record Dates
Last Update Posted: February 27, 2018
Last Verified: February 2018
Keywords provided by Actelion:
glioblastoma
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Macitentan
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Endothelin B Receptor Antagonists