GlioblastomaPhase 1NCT01851733
MRI-Guided Laser Surgery and Doxorubicin Hydrochloride in Treating Patients With Recurrent Glioblastoma Multiforme
A Phase 1 study testing MRI-guided Laser Heat Ablation (MLA), Doxorubicin and Blood draw - dendritic cells in people with Glioblastoma, run by Washington University School of Medicine at 1 site in United States.
Trial summary
This pilot clinical trial studies magnetic resonance imaging (MRI)-guided laser surgery (MLA) and doxorubicin hydrochloride in treating patients with recurrent glioblastoma multiforme. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- MRI-guided Laser Heat Ablation (MLA), Doxorubicin and Blood draw - dendritic cells
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Aug 2013to 30 May 2018
- 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 GBM; rare GBM variants, secondary GBM, and suspected secondary GBM are allowed.
- Unequivocal evidence of tumor progression by magnetic resonance imaging (MRI) scan.
- There must be an interval of at least 12 weeks from the completion of radiotherapy to study registration except if there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks from the completion of radiotherapy, the use of PET scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudoprogression.
- Candidate for MLA based on size, location, and shape of the recurrent tumor as determined by the performing neurosurgeon
- At least 18 years of age.
- Karnofsky performance status ≥ 60%.
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- Scheduled for MRI-guided Laser Ablation (MLA).
- Normal left ventricular ejection fraction on MUGA or echocardiogram within the past 1 year prior to registration for patients with history of congestive heart failure and/or coronary disease requiring medications other than aspirin, or known prior exposure to anthracycline chemotherapy.
- Adequate bone marrow and hepatic function as defined below (must be within 7 days of MLA):
- Absolute neutrophil count (ANC) ≥ 1500/mcl (G-CSF is allowed)
- Platelets ≥ 100,000/mcl
- Hemoglobin ≥ 9 (pRBC transfusion +/- ESA are allowed)
- ALT ≤ 3 x ULN
- AST ≤ 3 x ULN
- ALP ≤ 3 x ULN. If ALP is > 3 x ULN, GGT must be checked and be ≤ 3 x ULN.
- Bilirubin ≤ 2 x ULN
- At the time of registration, patient must have recovered from the toxic effects of prior therapy to no more than grade 1 toxicity.
- At the time of registration, patient must be at least 2 weeks from prior vincristine, 3 weeks from prior procarbazine, and 4 weeks from other prior cytotoxic chemotherapy.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- Prior treatment with doxorubicin and/or bevacizumab.
- Prior treatment with Gliadel wafer is allowed if it has been at least 3 months from placement.
- Previous treatment with complete cumulative doses of daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones that is equivalent to a total dose of 240 mg/m2 doxorubicin.
- More than 2 prior relapses.
- Currently receiving any other investigational agents that are intended as treatments of GBM.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to doxorubicin or other agents used in the study.
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, recent heart attack within the previous 12 months or severe heart problems, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and/or breastfeeding. Premenopausal women must have a negative serum pregnancy test within 14 days of study entry.
- Inability to undergo MRI due to personal and medical reasons.
- Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Pilot Study of Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Doxorubicin in the Treatment of Recurrent Glioblastoma Multiforme
This pilot clinical trial studies magnetic resonance imaging (MRI)-guided laser surgery (MLA) and doxorubicin hydrochloride in treating patients with recurrent glioblastoma multiforme. The blood brain barrier (BBB) is a separation of circulating blood from the tissue of the central nervous system, preventing substances in the blood from entering the brain. MLA disrupts the BBB around the tumor which may allow cancer-killing substances to be carried directly to the tumor and the surrounding area. Using MLA prior to chemotherapy may result in a greater concentration of drug in the tumor to kill the cancer cells while limiting side effects.
Read the detailed description
Evaluate imaging techniques (MRI) and blood tests (biomarkers) to help figure out the best time for chemotherapy to be initiated after the blood brain barrier is disrupted, as it is immediately following a procedure like MRI-guided laser ablation (MLA-Monteris Neuroblate).
- Conditions
- Glioblastoma
- Being tested
- MRI-guided Laser Heat Ablation (MLA), Doxorubicin, Blood draw - dendritic cells, Dynamic Susceptibility Contrast Magnetic Resonance Imaging
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI-guided Laser Heat Ablation (MLA)Device
DoxorubicinDrug
Also called Adriamycin®
Blood draw - dendritic cellsOther
The second 10 patients enrolled to Arm B:
- before MLA (up to 3 days before)
- 2 weeks after MLA
- 4 weeks after MLA
- every 2 weeks thereafter for up to 3 months after biopsy (provided there is no significant chemotherapy induced cytopenia)
Dynamic Susceptibility Contrast Magnetic Resonance ImagingDevice
Also called DSC-MRI
| Study group | Role | What they receive |
|---|---|---|
| Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks) | Experimental | * Patients undergo MLA (MRI-guided laser heat ablation). A subset of patients will have a biopsy at time of MLA.
* Beginning 6-8 weeks later, patients receive doxorubicin hydrochloride 20 mg/m2 intravenously (IV) over 5 minutes once weekly for 6 weeks.
* Biomarker blood draws will be drawn at different time points.
* DSC-MRI: no more than 2 weeks prior to MLA, within approximately 3 days after MLA, 2/4/6 weeks after MLA, 10 weeks after MLA only if 6-week scan shows prolonged disruption of the blood brain barrier, 14 weeks after MLA only if week 10 MRI shows contined blood brain barrier disruption, and every 8 weeks until disease progression (these scans do not have to be DSC-MRI) Receives: Device: MRI-guided Laser Heat Ablation (MLA); Drug: Doxorubicin; Other: Blood draw - dendritic cells; Device: Dynamic Susceptibility Contrast Magnetic Resonance Imaging |
| Arm C: (MLA, doxorubicin hydrochloride at 72 hours) | Experimental | * Patients undergo MLA (MRI-guided laser heat ablation).
* Beginning within 72 hours later, patients receive doxorubicin hydrochloride 20 mg/m2 IV over 5 minutes once weekly for 6 weeks.
* DSC-MRI: no more than 2 weeks prior to MLA, within approximately 3 days after MLA, 2/4/6 weeks after MLA, 10 weeks after MLA only if 6-week scan shows prolonged disruption of the blood brain barrier, 14 weeks after MLA only if week 10 MRI shows contined blood brain barrier disruption, and every 8 weeks until disease progression (these scans do not have to be DSC-MRI) Receives: Device: MRI-guided Laser Heat Ablation (MLA); Drug: Doxorubicin; Device: Dynamic Susceptibility Contrast Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ktrans from DSC-MRI
Using a 2 compartment model to calculate a the vascular transfer constant (Ktrans) which will provide a quantitative measure of blood brain barrier leakage
Measured: 6 weeks
Peritumoral permeability scores, measured by DSC-MRI and serum biomarkers
Pearson correlation coefficient (r) will be determined for each biomarker and Ktrans value. A minimum r=0.5 is required for inclusion for further analysis and will be used as a peritumoral permeability score. This score will then be correlated with the patient outcome data to determine whether it has a predictive value.
Measured: 6 weeks
6-month PFS (rate)
Assessed using RANO Response criteria. A log-rank test will be used to compare 6-PFS of Arm B and of Arm C to historical controls.
Measured: 6 months
Secondary outcomes (2)
Overall Survival
Date began MLA treatment to date of death from any cause. A log-rank test will be used to compare OS of Arm B and of Arm C to historical controls.
Measured: 2 years
Quality of Life
Using Karnofsky performance status and the mini-mental state evaluation to assess patient overall response to treatment.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study start13 Aug 2013
- Primary completion12 Apr 2018
- Study completion30 May 2018
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.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Foundation for Barnes-Jewish Hospital
- Responsible party
- Sponsor
- Investigators
- Milan Chheda, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01851733
- Sponsor's protocol ID
- 201305148
- Status last verified
- Aug 2021
- First submitted
- 7 May 2013
- Last updated
- 27 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Leuthardt EC, Duan C, Kim MJ, Campian JL, Kim AH, Miller-Thomas MM, Shimony JS, Tran DD. Hyperthermic Laser Ablation of Recurrent Glioblastoma Leads to Temporary Disruption of the Peritumoral Blood Brain Barrier. PLoS One. 2016 Feb 24;11(2):e0148613. doi: 10.1371/journal.pone.0148613. eCollection 2016.
PubMed 26910903
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Doxorubicin in the Treatment of Recurrent Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT01851733
- Acronym / sponsor ID
- 201305148
- Conditions
- Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- The Foundation for Barnes-Jewish Hospital
- Study start
- 13 Aug 2013 (actual)
- Primary completion
- 12 Apr 2018 (actual)
- Study completion
- 30 May 2018 (actual)
- First posted
- 10 May 2013 (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 pilot clinical trial studies magnetic resonance imaging (MRI)-guided laser surgery (MLA) and doxorubicin hydrochloride in treating patients with recurrent glioblastoma multiforme. The blood brain barrier (BBB) is a separation of circulating blood from the tissue of the central nervous system, preventing substances in the blood from entering the brain. MLA disrupts the BBB around the tumor which may allow cancer-killing substances to be carried directly to the tumor and the surrounding area. Using MLA prior to chemotherapy may result in a greater concentration of drug in the tumor to kill the cancer cells while limiting side effects.
Detailed description
Evaluate imaging techniques (MRI) and blood tests (biomarkers) to help figure out the best time for chemotherapy to be initiated after the blood brain barrier is disrupted, as it is immediately following a procedure like MRI-guided laser ablation (MLA-Monteris Neuroblate).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks) | Experimental | Device: MRI-guided Laser Heat Ablation (MLA), Drug: Doxorubicin, Other: Blood draw - dendritic cells, Device: Dynamic Susceptibility Contrast Magnetic Resonance Imaging* Patients undergo MLA (MRI-guided laser heat ablation). A subset of patients will have a biopsy at time of MLA. * Beginning 6-8 weeks later, patients receive doxorubicin hydrochloride 20 mg/m2 intravenously (IV) over 5 minutes once weekly for 6 weeks. * Biomarker blood draws will be drawn at different time points. * DSC-MRI: no more than 2 weeks prior to MLA, within approximately 3 days after MLA, 2/4/6 weeks after MLA, 10 weeks after MLA only if 6-week scan shows prolonged disruption of the blood brain barrier, 14 weeks after MLA only if week 10 MRI shows contined blood brain barrier disruption, and every 8 weeks until disease progression (these scans do not have to be DSC-MRI) |
| Arm C: (MLA, doxorubicin hydrochloride at 72 hours) | Experimental | Device: MRI-guided Laser Heat Ablation (MLA), Drug: Doxorubicin, Device: Dynamic Susceptibility Contrast Magnetic Resonance Imaging* Patients undergo MLA (MRI-guided laser heat ablation). * Beginning within 72 hours later, patients receive doxorubicin hydrochloride 20 mg/m2 IV over 5 minutes once weekly for 6 weeks. * DSC-MRI: no more than 2 weeks prior to MLA, within approximately 3 days after MLA, 2/4/6 weeks after MLA, 10 weeks after MLA only if 6-week scan shows prolonged disruption of the blood brain barrier, 14 weeks after MLA only if week 10 MRI shows contined blood brain barrier disruption, and every 8 weeks until disease progression (these scans do not have to be DSC-MRI) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically confirmed GBM; rare GBM variants, secondary GBM, and suspected secondary GBM are allowed.
- Unequivocal evidence of tumor progression by magnetic resonance imaging (MRI) scan.
- There must be an interval of at least 12 weeks from the completion of radiotherapy to study registration except if there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks from the completion of radiotherapy, the use of PET scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudoprogression.
- Candidate for MLA based on size, location, and shape of the recurrent tumor as determined by the performing neurosurgeon
- At least 18 years of age.
Key exclusion criteria (10 listed)
- Prior treatment with doxorubicin and/or bevacizumab.
- Prior treatment with Gliadel wafer is allowed if it has been at least 3 months from placement.
- Previous treatment with complete cumulative doses of daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones that is equivalent to a total dose of 240 mg/m2 doxorubicin.
- More than 2 prior relapses.
- Currently receiving any other investigational agents that are intended as treatments of GBM.
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 |
|---|---|---|
| MRI-guided Laser Heat Ablation (MLA) | Device | Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks), Arm C: (MLA, doxorubicin hydrochloride at 72 hours) |
| DoxorubicinAlso: Adriamycin® | Drug | Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks), Arm C: (MLA, doxorubicin hydrochloride at 72 hours) |
| Blood draw - dendritic cellsThe second 10 patients enrolled to Arm B: * before MLA (up to 3 days before) * 2 weeks after MLA * 4 weeks after MLA * every 2 weeks thereafter for up to 3 months after biopsy (provided there is no significant chemotherapy induced cytopenia) | Other | Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks) |
| Dynamic Susceptibility Contrast Magnetic Resonance ImagingAlso: DSC-MRI | Device | Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks), Arm C: (MLA, doxorubicin hydrochloride at 72 hours) |
Primary outcome
Ktrans from DSC-MRI
Time frame: 6 weeks
Using a 2 compartment model to calculate a the vascular transfer constant (Ktrans) which will provide a quantitative measure of blood brain barrier leakage
Peritumoral permeability scores, measured by DSC-MRI and serum biomarkers
Time frame: 6 weeks
Pearson correlation coefficient (r) will be determined for each biomarker and Ktrans value. A minimum r=0.5 is required for inclusion for further analysis and will be used as a peritumoral permeability score. This score will then be correlated with the patient outcome data to determine whether it has a predictive value.
6-month PFS (rate)
Time frame: 6 months
Assessed using RANO Response criteria. A log-rank test will be used to compare 6-PFS of Arm B and of Arm C to historical controls.
2 secondary outcomes
Overall Survival
Time frame: 2 years
Quality of Life
Time frame: 2 years
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 27 Aug 2021.
- Derived from this study: PubMed 26910903Leuthardt EC, Duan C, Kim MJ, Campian JL, Kim AH, Miller-Thomas MM, Shimony JS, Tran DD. Hyperthermic Laser Ablation of Recurrent Glioblastoma Leads to Temporary Disruption of the Peritumoral Blood Brain Barrier. PLoS One. 2016 Feb 24;11(2):e0148613. doi: 10.1371/journal.pone.0148613. eCollection 2016.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Milan Chheda, M.D. principal investigator
Washington University School of Medicine
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 MRI-guided Laser Heat Ablation (MLA), Doxorubicin and Blood draw - dendritic cells in people with Glioblastoma, run by Washington University School of Medicine 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 20 inclusion and 10 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 27 Aug 2021. 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?
Ktrans from DSC-MRI (time frame: 6 weeks). The study lists 3 primary outcomes in all. 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 NCT01851733, 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 27 Aug 2021.