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

Primary Purpose

Glioblastoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Macitentan in combination with RT and TMZ

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Macitentan in combination with RT & TMZ

Arm Description

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Plasma concentrations of endothelin-1

Plasma concentrations of macitentan and its metabolite

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

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

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

Number of adverse events (per Common Terminology Criteria for Adverse Events [CTCAE] criteria, version 4.03]) leading to premature discontinuation of study treatment

Number of subjects with marked laboratory abnormalities or abnormal electrocardiogram (ECG) findings

Change from baseline in pulse rate, systolic & diastolic blood pressure

Exploratory efficacy endpoint of proportion of subjects with progression free survival (PFS) at 6 and 12 months

Number of adverse events (per CTCAE] criteria, version 4.03]) as a measure of safety and tolerability.

Full Information

NCT ID

NCT02254954

First Posted

September 23, 2014

Last Updated

February 26, 2018

Sponsor

Actelion

1. Study Identification

Unique Protocol Identification Number

NCT02254954

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2018

Overall Recruitment Status

Terminated

Why Stopped

Sponsor decision due to low recruitment

Study Start Date

January 8, 2015 (Actual)

Primary Completion Date

September 29, 2016 (Actual)

Study Completion Date

September 29, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Actelion

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma

Keywords

glioblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Macitentan in combination with RT & TMZ

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Macitentan in combination with RT and TMZ

Other Intervention Name(s)

Temodar (temozolomide [TMZ]), macitentan, Radiotherapy

Intervention Description

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

Primary Outcome Measure Information:

Title

Time Frame

Start of treatment to week 10

Secondary Outcome Measure Information:

Title

Plasma concentrations of endothelin-1

Time Frame

Baseline, Weeks 2, 6, and 10

Title

Plasma concentrations of macitentan and its metabolite

Time Frame

Baseline, Weeks 2 and 6

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Facility Information:

Facility Name

MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

Investigational Site Web Address

Learn more about this trial

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

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