Macitentan in Combo With Dose-dense Temozolomide in Patients With Recurrent Glioblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Actelion
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01499251
First received: December 20, 2011
Last updated: August 30, 2013
Last verified: August 2013
  Purpose

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 on the recommended macitentan and dose-dense temozolomide dosing schedule derived 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 The study will end when all patients (excluding those prematurely withdrawn or lost to follow-up) in each part of the study have completed a visit at month 12.


Condition Intervention Phase
Glioblastoma
Drug: Phase 1 Dose Escalation
Drug: Phase 1b
Drug: Ancillary Study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/1b, Open-label Study in Patients With Recurrent Glioblastoma to Assess the Safety and Tolerability of Macitentan in Combination With Dose-dense Temozolomide

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • determine the maximum tolerated dose of macitentan in combination with dose-dense temozolomide [ Time Frame: Phase I Dose Escalation period (Dose-Limiting Toxicity from Baseline to 28 days for each dose level) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • number of patients with premature treatment discontinuation, proportion of patients with PFS at 6 months and other measures [ Time Frame: participants will be followed up for the duration of combination treatment, an expected average of 9-12 months. ] [ Designated as safety issue: Yes ]
    Number of participants with Adverse Events leading to premature treatment discontinuation, number of patients with marked laboratory abnormalities, change from baseline in systolic & diastolic blood pressure and heart rate on a monthly basis until end of combination treatment. Exploratory Efficacy endpoint of proportion of patients with PFS at 6 months


Estimated Enrollment: 48
Study Start Date: December 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Macitentan
Macitentan in combination with dose-dense temozolomide
Drug: Phase 1 Dose Escalation

macitentan 30, 60, 90 mg or higher in 30mg dose increments, up to 150 mg, unless otherwise decided by the Safety Monitoring Committee.

Dose-dense temozolomide 150mg/m2 body surface area alternating 1 week on 1 week off.

Other Names:
  • Macitentan
  • dose-dense temozolomide
Drug: Phase 1b

macitentan given orally and daily at dose/schedule determined from the dose escalation period.

dose-dense temozolomide 150mg/m2 body surface area alternating 1 week on 1 week off.

Other Names:
  • Macitentan
  • dose-dense temozolomide
Drug: Ancillary Study

macitentan dosed initially for 8-14 days prior to craniotomy, then treatment interrupted from time of craniotomy until 7 days before start of dose dense temozolomide therapy.

dose-dense temozolomide 150mg/m2 body surface area alternating 1 week on 1 week off.

Other Names:
  • Macitentan
  • dose-dense temozolomide

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Patients at least 18 years of age
  • Histologically confirmed glioblastoma multiforme or gliosarcoma
  • Recurrent disease with an interval of at least 3 months following initial radiotherapy and temozolomide
  • Interval of at least 3 weeks between end of surgery for recurrent disease and start of protocol (if applicable)
  • KPS 60% or higher
  • Adequate bone marrow function

Exclusion Criteria

  • Histology other than astrocytoma grade IV or gliosarcoma
  • Tumor foci below the tentorium or cranial vault
  • Glioblastoma or gliosarcoma disease with leptomeningeal spread
  • Elevated serum aspartate aminotransferase, alanine aminotransferase, or bilirubin (unless there is medical justification for bilirubin elevation, and aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase are normal)
  • Moderate to severe hepatic impairment
  • Confirmed systolic blood pressure < 100 mmHg or diastolic blood pressure < 50 mmHg
  • History of orthostatic hypotension
  • Renal insufficiency
  • Prior chemotherapy for recurrent glioblastoma with nitrosourea compounds or bevacizumab
  • Prior focal radiotherapy
  • Severe, active co-morbidity (e.g. cardiac disease; respiratory disease; chronic hepatitis; hematological and bone marrow diseases; severe malabsorption)
  • No other active cancer
  • No concurrent cytochrome P450 3A4 inducers
  • No concurrent strong cytochrome P450 3A4 inhibitors
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01499251

Locations
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Charles Conrad, MD    713-792-2883      
Sponsors and Collaborators
Actelion
  More Information

No publications provided

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01499251     History of Changes
Other Study ID Numbers: AC-055-115
Study First Received: December 20, 2011
Last Updated: August 30, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Actelion:
glioblastoma

Additional relevant MeSH terms:
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
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2014