GlioblastomaPhase 1NCT02254954
Clinical Study on Macitentan, RT and TMZ Concurrent Therapy Followed by Maintenance Macitentan and TMZ in Newly Diagnosed Glioblastoma
A Phase 1 study testing Macitentan in combination with RT and TMZ in people with Glioblastoma, run by Actelion at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Macitentan in combination with RT and TMZ
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jan 2015to 29 Sep 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- Macitentan in combination with RT and TMZ
- Keywords
- glioblastoma
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Macitentan in combination with RT and TMZDrug
Also called Temodar (temozolomide [TMZ]), macitentan, Radiotherapy
Escalating doses of macitentan in combination with RT and TMZ, and maintenance TMZ.
| Study group | Role | What they receive |
|---|---|---|
| Macitentan in combination with RT & TMZ | Experimental | Escalating doses of macitentan in combination with RT and TMZ, and maintenance TMZ. Receives: Drug: Macitentan in combination with RT and TMZ |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Start of treatment to week 10
Secondary outcomes (10)
Plasma concentrations of endothelin-1
Measured: Baseline, Weeks 2, 6, and 10
Plasma concentrations of macitentan and its metabolite
Measured: 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
Measured: Week 4
Peak plasma concentration (Cmax) of macitentan during one dosing interval for subjects treated with doses of macitentan 150 mg or higher
Measured: 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
Measured: Week 4
Number of adverse events (per Common Terminology Criteria for Adverse Events [CTCAE] criteria, version 4.03]) leading to premature discontinuation of study treatment
Measured: Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days of follow-up
Number of subjects with marked laboratory abnormalities or abnormal electrocardiogram (ECG) findings
Measured: Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days of follow-up
Change from baseline in pulse rate, systolic & diastolic blood pressure
Measured: Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days follow-up
Exploratory efficacy endpoint of proportion of subjects with progression free survival (PFS) at 6 and 12 months
Measured: 6 and 12 months after the start of treatment
Number of adverse events (per CTCAE] criteria, version 4.03]) as a measure of safety and tolerability.
Measured: Starting from first dose of concurrent therapy (i.e., macitentan, TMZ, RT) until the end of treatment plus 30 days of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2014 (estimated)
- Study start8 Jan 2015
- Primary completion29 Sep 2016
- Study completion29 Sep 2016
Why it stopped: Sponsor decision due to low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02254954
- Sponsor's protocol ID
- AC-055-118
- Status last verified
- Feb 2018
- First submitted
- 23 Sep 2014
- Last updated
- 27 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02254954
- Acronym / sponsor ID
- AC-055-118
- Conditions
- Glioblastoma
- Keywords
- glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision due to low recruitment
- Enrolment
- 30 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- 8 Jan 2015 (actual)
- Primary completion
- 29 Sep 2016 (actual)
- Study completion
- 29 Sep 2016 (actual)
- First posted
- 2 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Macitentan in combination with RT & TMZ | Experimental | Drug: Macitentan in combination with RT and TMZEscalating doses of macitentan in combination with RT and TMZ, and maintenance TMZ. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Macitentan in combination with RT and TMZAlso: Temodar (temozolomide [TMZ]), macitentan, RadiotherapyEscalating doses of macitentan in combination with RT and TMZ, and maintenance TMZ. | Drug | Macitentan in combination with RT & TMZ |
Primary outcome
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
10 secondary outcomes
Plasma concentrations of endothelin-1
Time frame: Baseline, Weeks 2, 6, and 10
Plasma concentrations of macitentan and its metabolite
Time frame: 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
Time frame: Week 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
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
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
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
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
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
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
Results and safety
The study was stopped early (reason given: Sponsor decision due to low recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2018.
- Investigational Site Web AddressLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Macitentan in combination with RT and TMZ in people with Glioblastoma, run by Actelion at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor decision due to low recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2018.