GlioblastomaPhase 1NCT01499251
Clinical Study on the Safety and Tolerability of Macitentan in Combination With Dose-dense Temozolomide in Patients With Recurrent Glioblastoma
A Phase 1 study testing Phase 1 Dose Escalation, Phase 1b and Ancillary Study in people with Glioblastoma, run by Actelion at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Phase 1 Dose Escalation, Phase 1b and Ancillary Study
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Apr 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
- 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 therapy for patients who have undergone surgery for recurrent disease
- KPS 60% or higher
- Adequate bone marrow function Women of childbearing potential must have a negative serum beta-HCG pregnancy test documented within 14 days prior to study initiation.
- Women of childbearing potential must agree to use two reliable methods of contraception from screening and up to 30 days after discontinuation of study treatment.
- Males not naturally or surgically sterile, who have a female partner of childbearing potential, must agree to use two reliable methods of contraception from screening and up to 30 days after discontinuation of study treatment.
Who cannot join
- Histology other than astrocytoma grade IV (GBM or gliosarcoma)
- Tumor foci below the tentorium or or beyond the cranial vault
- Glioblastoma or gliosarcoma disease with leptomeningeal spread
- Patients with a history of any other cancer, unless in complete remission, and off all therapy for that disease for a minimum of 5 years
- 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
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- Confirmed systolic blood pressure < 100 mmHg or diastolic blood pressure < 50 mmHg
- History of orthostatic hypotension
- Renal insufficiency or serum creatinine above the normal reference range
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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 of two doses of macitentan and dose-dense temozolomide selected 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 and 30 days of safety follow-up.
- Conditions
- Glioblastoma
- Being tested
- Phase 1 Dose Escalation, Phase 1b, Ancillary Study
- 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.
Phase 1 Dose EscalationDrug
Also called dose-dense temozolomide, Macitentan
Macitentan 30, 60, 90 mg or higher in 30 mg dose increments, given orally, up to 150 mg, then 225 mg, 300 mg and 375 mg, unless otherwise decided by the Safety Monitoring Committee. Dose-dense temozolomide 150 mg/m2 body surface area alternating 1 week on 1 week off.
Phase 1bDrug
Also called Macitentan, dose-dense temozolomide
Macitentan given orally and daily at doses/schedule determined from the dose escalation period. Dose-dense temozolomide 150mg/m2 body surface area alternating 1 week on 1 week off.
Ancillary StudyDrug
Also called dose-dense temozolomide, Macitentan
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 150 mg/m2 body surface area alternating 1 week on 1 week off.
| Study group | Role | What they receive |
|---|---|---|
| Macitentan | Experimental | Macitentan in combination with dose-dense temozolomide Receives: Drug: Phase 1 Dose Escalation; Drug: Phase 1b; Drug: Ancillary Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose of macitentan in combination with dose-dense temozolomide
Measured: Phase I Dose Escalation period (Dose-Limiting Toxicity from Baseline to 28 days for each dose level)
Secondary outcomes (6)
Number of patients with treatment-emergent adverse events (AEs) and serious AEs
for all study periods
Measured: Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.
Number of patients with AEs leading to premature discontinuation of study treatment
for all study periods
Measured: Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.
Incidence of treatment-emergent* marked laboratory abnormalities
for all study periods
Measured: Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.
Number of patients with treatment-emergent ECG abnormalities
for all study periods
Measured: Up to 30 days after discontinuation of macitentan
Change from baseline in vital signs
for all study periods: systolic and diastolic blood pressure [supine and standing], average of the two measurements and pulse rate.
Measured: Up to 30 days after discontinuation of macitentan
Occurrence of at least grade 2 ALT and/or AST elevation
for all study periods
Measured: Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionJan 2016
- Study completionApr 2016
Why it stopped: Results did not clearly support continuing development in recurrent GBM
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01499251
- Sponsor's protocol ID
- AC-055-115
- Status last verified
- May 2016
- First submitted
- 20 Dec 2011
- Last updated
- 5 May 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Weathers SP, Rood-Breithaupt J, de Groot J, Thomas G, Manfrini M, Penas-Prado M, Puduvalli VK, Zwingelstein C, Yung WKA. Results of a phase I trial to assess the safety of macitentan in combination with temozolomide for the treatment of recurrent glioblastoma. Neurooncol Adv. 2021 Oct 2;3(1):vdab141. doi: 10.1093/noajnl/vdab141. eCollection 2021 Jan-Dec.
PubMed 34693288
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01499251
- Acronym / sponsor ID
- AC-055-115
- Conditions
- Glioblastoma
- Keywords
- glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Results did not clearly support continuing development in recurrent GBM
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Jan 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 26 Dec 2011 (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 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 of two doses of macitentan and dose-dense temozolomide selected 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 and 30 days of safety follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Macitentan | Experimental | Drug: Phase 1 Dose Escalation, Drug: Phase 1b, Drug: Ancillary StudyMacitentan in combination with dose-dense temozolomide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically confirmed glioblastoma multiforme or gliosarcoma
- Recurrent disease with an:
- KPS 60% or higher
- Adequate bone marrow function Women of childbearing potential must have a negative serum beta-HCG pregnancy test documented within 14 days prior to study initiation.
- Women of childbearing potential must agree to use two reliable methods of contraception from screening and up to 30 days after discontinuation of study treatment.
Key exclusion criteria (16 listed)
- Histology other than astrocytoma grade IV (GBM or gliosarcoma)
- Tumor foci below the tentorium or or beyond the cranial vault
- Glioblastoma or gliosarcoma disease with leptomeningeal spread
- Patients with a history of any other cancer, unless in complete remission, and off all therapy for that disease for a minimum of 5 years
- 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)
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 |
|---|---|---|
| Phase 1 Dose EscalationAlso: dose-dense temozolomide, MacitentanMacitentan 30, 60, 90 mg or higher in 30 mg dose increments, given orally, up to 150 mg, then 225 mg, 300 mg and 375 mg, unless otherwise decided by the Safety Monitoring Committee. Dose-dense temozolomide 150 mg/m2 body surface area alternating 1 week on 1 week off. | Drug | Macitentan |
| Phase 1bAlso: Macitentan, dose-dense temozolomideMacitentan given orally and daily at doses/schedule determined from the dose escalation period. Dose-dense temozolomide 150mg/m2 body surface area alternating 1 week on 1 week off. | Drug | Macitentan |
| Ancillary StudyAlso: dose-dense temozolomide, MacitentanMacitentan 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 150 mg/m2 body surface area alternating 1 week on 1 week off. | Drug | Macitentan |
Primary outcome
To 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)
6 secondary outcomes
Number of patients with treatment-emergent adverse events (AEs) and serious AEs
Time frame: Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.
Number of patients with AEs leading to premature discontinuation of study treatment
Time frame: Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.
Incidence of treatment-emergent* marked laboratory abnormalities
Time frame: Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.
Number of patients with treatment-emergent ECG abnormalities
Time frame: Up to 30 days after discontinuation of macitentan
Change from baseline in vital signs
Time frame: Up to 30 days after discontinuation of macitentan
Occurrence of at least grade 2 ALT and/or AST elevation
Time frame: Participants will be followed up for the duration of combination treatment, an expected average of 9-12 months.
Results and safety
The study was stopped early (reason given: Results did not clearly support continuing development in recurrent GBM). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2016.
- Derived from this study: PubMed 34693288Weathers SP, Rood-Breithaupt J, de Groot J, Thomas G, Manfrini M, Penas-Prado M, Puduvalli VK, Zwingelstein C, Yung WKA. Results of a phase I trial to assess the safety of macitentan in combination with temozolomide for the treatment of recurrent glioblastoma. Neurooncol Adv. 2021 Oct 2;3(1):vdab141. doi: 10.1093/noajnl/vdab141. eCollection 2021 Jan-Dec.
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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 Phase 1 Dose Escalation, Phase 1b and Ancillary Study 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 16 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 5 May 2016. 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: Results did not clearly support continuing development in recurrent GBM). 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?
To 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01499251, which also lists 1 linked publication.
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 5 May 2016.