MRI-Guided Laser Surgery and Doxorubicin Hydrochloride in Treating Patients With Recurrent Glioblastoma Multiforme

August 26, 2021 updated by: Washington University School of Medicine

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
37

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria - Arms B and C:

  • 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%.
  • 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).

Exclusion Criteria - Arms B and C:

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)
  • 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)
Drug: Doxorubicin
Other Names:
  • Adriamycin®
Device: MRI-guided Laser Heat Ablation (MLA)
Other: Blood draw - dendritic cells

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)
Device: Dynamic Susceptibility Contrast Magnetic Resonance Imaging
Other Names:
  • DSC-MRI
Experimental: Arm C: (MLA, doxorubicin hydrochloride at 72 hours)
  • 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)
Drug: Doxorubicin
Other Names:
  • Adriamycin®
Device: MRI-guided Laser Heat Ablation (MLA)
Device: Dynamic Susceptibility Contrast Magnetic Resonance Imaging
Other Names:
  • DSC-MRI

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
6 weeks
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 weeks
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.
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 2 years
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.
2 years
Quality of Life
Time Frame: 2 years
Using Karnofsky performance status and the mini-mental state evaluation to assess patient overall response to treatment.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The Foundation for Barnes-Jewish Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 13, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 12, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 30, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 7, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 7, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 10, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 27, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 26, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201305148

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings