Glioblastoma Multiforme (GBM)Phase 1NCT02202993
TAU-2014-1: Mibefradil and Hypofractionated Re-Irradiation Therapy in Recurrent GBM
A Phase 1 study testing Mibefradil with Radiation in people with Glioblastoma Multiforme (GBM), run by Cavion, Inc. at 1 site in United States.
Trial summary
This is a dose-escalation study that will assess the safety and determine the maximum tolerated dose (MTD) of mibefradil dihydrochloride, a partially selective T-type calcium channel blocker, combined with hypofractionated radiation therapy (RT) in subjects with recurrent glioblastoma multiforme (GBM). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Glioblastoma Multiforme (GBM)
- What is being tested?
- Mibefradil with Radiation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to 29 Sep 2017
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sign written informed consent.
- Histologically proven glioblastoma multiforme (GBM) that is progressive or recurrent following standard radiation therapy (RT) and temozolomide (i.e., at least "biopsy-proven" recurrent disease). Previous salvage therapies after first recurrence are permitted.
- Measurable contrast-enhancing progressive or recurrent GBM (single or multiple lesions) by MRI imaging with an interval of greater than or equal to 6 months between recurrence and completion of prior radiotherapy.
- Patients who have not passed an interval of at least 6 months may still be eligible if they meet the following criteria: convincing histologic evidence of disease recurrence which is not thought to predominantly represent radionecrosis, standard focal external beam radiation therapy (EBRT) treatment with acceptable doses to tumor and normal tissue which suggest re-irradiation is feasible.
- Prior history of standard dose focal RT to 60 Gy in 30 fractions or 59.4 Gy in 1.8 Gy fractions, or equivalent or lower doses. Patients who have received prior treatment with non-standard RT dose and fractionation schemes are still eligible, provided they have only received a single course of RT. However, subjects treated with interstitial brachytherapy or single-fraction stereotactic radiosurgery are not eligible for this trial.
- Karnofsky performance status ≥60%
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- Clinical laboratory:
- absolute neutrophil count >1,500/microliter (mcL)
- platelets >100,000/mcL
- hemoglobin > 9 g/ dL serum bilirubin < 1.5 times the upper limit of normal (ULN); unless due to Gilbert's syndrome (in which <2 times ULN acceptable)
- serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 2.5 times ULN
- serum Creatinine < 1.5 times ULN
- Women of childbearing potential and men must agree to use adequate contraception.
- Women of childbearing potential must have a negative pregnancy test prior to treatment.
- Recovered to Common Toxicity Criteria for Adverse Effects (CTCAE) grade ≤ 2 from prior therapy toxicities
- 30 days since previous treatment of brain tumor with any other agents.
- Stable or decreasing corticosteroid regimen (no increase for 7 days) prior to the start of treatment.
- >18 years of age
Who cannot join
- Concurrent malignancy except curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix, breast, or bladder. Subjects with prior malignancies must be disease-free for ≥ five years.
- Biopsy-confirmed exclusive radionecrosis after initial GBM therapy.
- Receipt of other investigational agents or anti-cancer agents within 30 days
- Serious concurrent infection or medical illness, which would jeopardize the ability of the subject to receive treatment safely.
- Systolic blood pressure <100 mm Hg, diastolic <60 mm Hg.
- Requirement for calcium channel blocker for blood pressure control that cannot be switched to an antihypertensive with an alternative mechanism of action. Permitted anti-hypertensive medications include: chlorothiazide, hydrochlorothiazide, atenolol, nadolol, enalapril, lisinopril, eprosartan, and irbesartan.
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- Known, active hepatitis.
- corrected QT (QTc) interval ≥ 450 milliseconds (mSec) for males or ≥470 mSec for females. PR interval > 250 mSec for males and females
- High-grade (second degree or above) atria-ventricular (AV) block or persistent sinus bradycardia of less than 50 beats per minute (BPM).
- Known HIV-positivity
- Pregnant and/or lactating women
- Anti-arrhythmia medication other than beta-blockers or digoxin.
- Treatment with concurrent enzyme-inducing anti-epileptic drugs (EIAEDs).
- Treatment with unfractionated heparin. Patients taking an anticoagulant must use warfarin or a low molecular weight heparin.
- Treatment with specified drugs that are substrates of cytochrome 3A4 (CYP3A4), cytochrome 2D6 (CYP2D6), cytochrome 1A2 (CYP1A2)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: TAU-2014-1: Phase I Trial of Mibefradil Dihydrochloride With Hypofractionated Re-Irradiation Therapy in Treating Patients With Recurrent Glioblastoma Multiforme (GBM)
This is a dose-escalation study that will assess the safety and determine the maximum tolerated dose (MTD) of mibefradil dihydrochloride, a partially selective T-type calcium channel blocker, combined with hypofractionated radiation therapy (RT) in subjects with recurrent glioblastoma multiforme (GBM).
Read the detailed description
Patients will receive mibefradil dihydrochloride, which will be dose escalated from 150mg/day until the maximum tolerated dose (MTD) is determined, or until a dose of 350 mg/day is reached using a standard 3 + 3 design. Mibefradil dihydrochloride will be dosed orally in 4 divided doses per day for 17 consecutive days to the MTD. The MTD will be determined according to dose-limiting toxicities (DLTs) graded using the Common Terminology Criteria for Adverse Events version 4.0. Radiation therapy (RT) consists of 5 fractions of 600 centigray (cGy) each, delivered over 2 consecutive weeks for a total dose of 3,000 cGy, using stereotactic, intensity-modulated radiation therapy (IMRT).
The primary endpoint of the study is to determine the MTD of mibefradil dihydrochloride when given with concurrent hypofractionated RT. Secondary and tertiary endpoints include evaluating the efficacy of mibefradil dihydrochloride and RT in terms of progression-free survival (PFS) and overall survival (OS), and to perform translational research on resected tumor tissue.
- Conditions
- Glioblastoma Multiforme (GBM)
- Being tested
- Mibefradil with Radiation
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mibefradil with RadiationDrug
Also called mibefradil, mibefradil dihydrochloride, Posicor, hypo fractionated radiation
Patients will receive mibefradil dihydrochloride, which will be dose escalated from 150mg/day until the maximum tolerated dose (MTD) is determined, or until a dose of 350 mg/day is reached using a standard 3 + 3 design. Mibefradil dihydrochloride will be dosed orally in 4 divided doses per day for 17 consecutive days to the MTD.
This will be given concurrently with hypofractionated radiation therapy.
| Study group | Role | What they receive |
|---|---|---|
| Mibefradil with Radiation | Experimental | Patients will receive mibefradil dihydrochloride, which will be dose escalated from 150mg/day until the maximum tolerated dose (MTD) is determined, or until a dose of 350 mg/day is reached using a standard 3 + 3 design. Mibefradil dihydrochloride will be dosed orally in 4 divided doses per day for 17 consecutive days to the MTD.
This will be given concurrently with hypofractionated radiation therapy. Receives: Drug: Mibefradil with Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities
Measured: Monitored continuously, 27 months
Maximum tolerated dose
Measured: Monitored continuously, 27 months
Secondary outcomes (4)
Adverse events
Measured: 27 months
Mibefradil dihydrochloride steady state plasma concentrations
Measured: 27 months
Progression-free survival of treated patients
Measured: 27 months
Overall survival of treated patients
Measured: 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2014 (estimated)
- Study startAug 2014
- Primary completion29 Sep 2017
- Study completion29 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma Multiforme (GBM)Studies 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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cavion, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Yale University
- Responsible party
- Sponsor
- Investigators
- Ranjit S Bindra, MD PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02202993
- Sponsor's protocol ID
- 1406014067
- Status last verified
- Apr 2019
- First submitted
- 15 Jul 2014
- Last updated
- 24 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TAU-2014-1: Phase I Trial of Mibefradil Dihydrochloride With Hypofractionated Re-Irradiation Therapy in Treating Patients With Recurrent Glioblastoma Multiforme (GBM)
- ClinicalTrials.gov ID
- NCT02202993
- Acronym / sponsor ID
- 1406014067
- Conditions
- Glioblastoma Multiforme (GBM)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Cavion, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Yale University
- Study start
- Aug 2014
- Primary completion
- 29 Sep 2017 (actual)
- Study completion
- 29 Sep 2017 (actual)
- First posted
- 29 Jul 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 dose-escalation study that will assess the safety and determine the maximum tolerated dose (MTD) of mibefradil dihydrochloride, a partially selective T-type calcium channel blocker, combined with hypofractionated radiation therapy (RT) in subjects with recurrent glioblastoma multiforme (GBM).
Detailed description
Patients will receive mibefradil dihydrochloride, which will be dose escalated from 150mg/day until the maximum tolerated dose (MTD) is determined, or until a dose of 350 mg/day is reached using a standard 3 + 3 design. Mibefradil dihydrochloride will be dosed orally in 4 divided doses per day for 17 consecutive days to the MTD. The MTD will be determined according to dose-limiting toxicities (DLTs) graded using the Common Terminology Criteria for Adverse Events version 4.0. Radiation therapy (RT) consists of 5 fractions of 600 centigray (cGy) each, delivered over 2 consecutive weeks for a total dose of 3,000 cGy, using stereotactic, intensity-modulated radiation therapy (IMRT).
The primary endpoint of the study is to determine the MTD of mibefradil dihydrochloride when given with concurrent hypofractionated RT. Secondary and tertiary endpoints include evaluating the efficacy of mibefradil dihydrochloride and RT in terms of progression-free survival (PFS) and overall survival (OS), and to perform translational research on resected tumor tissue.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mibefradil with Radiation | Experimental | Drug: Mibefradil with RadiationPatients will receive mibefradil dihydrochloride, which will be dose escalated from 150mg/day until the maximum tolerated dose (MTD) is determined, or until a dose of 350 mg/day is reached using a standard 3 + 3 design. Mibefradil dihydrochloride will be dosed orally in 4 divided doses per day for 17 consecutive days to the MTD. This will be given concurrently with hypofractionated radiation therapy. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Sign written informed consent.
- Histologically proven glioblastoma multiforme (GBM) that is progressive or recurrent following standard radiation therapy (RT) and temozolomide (i.e., at least "biopsy-proven" recurrent disease). Previous salvage therapies after first recurrence are permitted.
- Measurable contrast-enhancing progressive or recurrent GBM (single or multiple lesions) by MRI imaging with an interval of greater than or equal to 6 months between recurrence and completion of prior radiotherapy.
- Patients who have not passed an interval of at least 6 months may still be eligible if they meet the following criteria: convincing histologic evidence of disease recurrence which is not thought to predominantly represent radionecrosis, standard focal external beam radiation therapy (EBRT) treatment with acceptable doses to tumor and normal tissue which suggest re-irradiation is feasible.
- Prior history of standard dose focal RT to 60 Gy in 30 fractions or 59.4 Gy in 1.8 Gy fractions, or equivalent or lower doses. Patients who have received prior treatment with non-standard RT dose and fractionation schemes are still eligible, provided they have only received a single course of RT. However, subjects treated with interstitial brachytherapy or single-fraction stereotactic radiosurgery are not eligible for this trial.
Key exclusion criteria (15 listed)
- Concurrent malignancy except curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix, breast, or bladder. Subjects with prior malignancies must be disease-free for ≥ five years.
- Biopsy-confirmed exclusive radionecrosis after initial GBM therapy.
- Receipt of other investigational agents or anti-cancer agents within 30 days
- Serious concurrent infection or medical illness, which would jeopardize the ability of the subject to receive treatment safely.
- Systolic blood pressure <100 mm Hg, diastolic <60 mm Hg.
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 |
|---|---|---|
| Mibefradil with RadiationAlso: mibefradil, mibefradil dihydrochloride, Posicor, hypo fractionated radiationPatients will receive mibefradil dihydrochloride, which will be dose escalated from 150mg/day until the maximum tolerated dose (MTD) is determined, or until a dose of 350 mg/day is reached using a standard 3 + 3 design. Mibefradil dihydrochloride will be dosed orally in 4 divided doses per day for 17 consecutive days to the MTD. This will be given concurrently with hypofractionated radiation therapy. | Drug | Mibefradil with Radiation |
Primary outcome
Dose limiting toxicities
Time frame: Monitored continuously, 27 months
Maximum tolerated dose
Time frame: Monitored continuously, 27 months
4 secondary outcomes
Adverse events
Time frame: 27 months
Mibefradil dihydrochloride steady state plasma concentrations
Time frame: 27 months
Progression-free survival of treated patients
Time frame: 27 months
Overall survival of treated patients
Time frame: 27 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2019.
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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.
Ranjit S Bindra, MD PhD principal investigator
Yale University
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 Mibefradil with Radiation in people with Glioblastoma Multiforme (GBM), run by Cavion, Inc. 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 18 inclusion and 15 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: finished, as of the sponsor's last update on 24 Jul 2019. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Dose limiting toxicities (time frame: Monitored continuously, 27 months). The study lists 2 primary outcomes in all. 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 24 Jul 2019.