Using MRI-Guided Laser Heat Ablation to Induce Disruption... | NCT02372409

NCT02372409

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A (MRI-guided laser ablation)	Experimental	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression	Device: MRI-guided laser ablation Device: Dynamic contrast-enhanced (DCE) MRI Device: Dynamic susceptibility contrast (DSC) MRI
Arm B (MRI-guided laser ablation, doxorubicin, etoposide)	Experimental	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Within 7 days of MLA (range 2-14 days) doxorubicin will be given intravenously on an outpatient basis weekly for 6 weeks at a dose of 25 mg/m^2 over 5-30 minutes Following the completion of doxorubin, etoposide 50 mg/m^2/day will be given orally for 21 days of each 28-day cycle (treatment can continue up to 24 cycles) Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA every 8 weeks (+/- 7 days) until 2 years have elapsed or disease progression, whichever comes first	Device: MRI-guided laser ablation Drug: Doxorubicin Drug: Etoposide Device: Dynamic contrast-enhanced (DCE) MRI Device: Dynamic susceptibility contrast (DSC) MRI

Name	Type	Description	Arm Group Labels	Other Names
MRI-guided laser ablation	Device		Arm A (MRI-guided laser ablation) Arm B (MRI-guided laser ablation, doxorubicin, etoposide)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Arm A Only: Number of Participants With Progression-free Survival (PFS)	PFS is followed from start of treatment to time of progression or death, whichever occurs first.	Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)
Arm A Only: Overall Survival (OS) as Measured by Number of Participants Alive at 5 Years		Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)
Arm B Only: Number of Participants With Progression-free Survival (PFS)	PFS is followed from start of treatment to time of progression or death, whichever occurs first.	At 6 months

Secondary Outcomes

Measure	Description	Time Frame
Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status	Score ranges from 100% to 10%. A higher score indicates that the patient has a more normal quality of life.	At 1 year post-MLA
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

ARM A

Presumed pediatric gliomas (grades I-IV) on MRI that are determined to be candidates for MLA by the treating neurosurgeon
Age 3 to ≤ 21
Karnofsky/Lansky performance status ≥ 60%

ARM B

Recurrent pediatric brain tumors determined candidates for MLA as determined by the treating neurosurgeon.
Unequivocal evidence of tumor progression by MRI
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 evidence of tumor recurrence and pseudoprogression.
Recurrent lesions with dimension and contour that are determined by the treating neurosurgeon to be appropriate for MLA.
Age 3 to ≤ 21
Karnofsky/Lansky performance status ≥ 60%
Adequate cardiac function as determined by a shortening fraction ≥ 27% or left ventricular ejection fraction ≥ 50% by echocardiogram within the past 1 year prior to registration.
Prior anthracycline therapy does not exceed 200 mg/m^2 total cumulative dose.
Adequate bone marrow and hepatic function as defined below (must be within 7 days of MLA):
- Absolute neutrophil count (ANC) ≥ 1000/mcl (G-CSF is allowed)
- Platelets ≥ 100 K/cumm
- Hemoglobin ≥ 9 g/dL (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 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:

ARM A

Currently receiving or scheduled to receive any other therapies intended to treat the newly diagnosed glioma prior to MLA and the first post-MLA blood collection for correlative studies.
Multi-focal or metastatic disease.
Pregnant and/or breastfeeding. Premenopausal women must have a negative serum or urine pregnancy test within 14 days of study entry.
Inability to undergo MRI due to personal or medical reasons.
Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.

ARM B

Prior treatment with bevacizumab within 12 weeks of study entry.
Previous treatment with complete cumulative doses of daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones that is equivalent to a total dose of > 200 mg/m2 doxorubicin.
More than 2 prior relapses (not counting the current relapse being treated on this study).
Currently receiving any other investigational agents that are intended as treatments of the relapsed tumor.
Multi-focal or metastatic disease.
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 or urine pregnancy test within 14 days of study entry.
Inability to undergo MRI due to personal or medical reasons.
Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.

Contacts/Locations Module

Name	Affiliation	Role
Andrew Cluster, M.D.	Washington University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Washington University School of Medicine		St Louis	Missouri	63110	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
10602854	Background	Holodny AI, Nusbaum AO, Festa S, Pronin IN, Lee HJ, Kalnin AJ. Correlation between the degree of contrast enhancement and the volume of peritumoral edema in meningiomas and malignant gliomas. Neuroradiology. 1999 Nov;41(11):820-5. doi: 10.1007/s002340050848.
21082374	Background	Kassner A, Thornhill R. Measuring the integrity of the human blood-brain barrier using magnetic resonance imaging. Methods Mol Biol. 2011;686:229-45. doi: 10.1007/978-1-60761-938-3_10.

Label	URL
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Aug 11, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression
BG001	Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Within 7 days of MLA (range 2-14 days) doxorubicin will be given intravenously on an outpatient basis weekly for 6 weeks at a dose of 25 mg/m^2 over 5-30 minutes Following the completion of doxorubin, etoposide 50 mg/m^2/day will be given orally for 21 days of each 28-day cycle (treatment can continue up to 24 cycles) Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA every 8 weeks (+/- 7 days) until 2 years have elapsed or disease progression, whichever comes first
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0005 BG0011 BG0026

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00011(4 to 15) BG00112(12 to 12) BG00211.5(4 to 15)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002 BG0010 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0005 BG0011 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Arm A Only: Number of Participants With Progression-free Survival (PFS)

PFS is followed from start of treatment to time of progression or death, whichever occurs first.

This outcome measure is for Arm A participants only.

Posted

Count of Participants

Participants

Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)

ID	Title	Description
OG000	Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression
OG001	Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Within 7 days of MLA (range 2-14 days) doxorubicin will be given intravenously on an outpatient basis weekly for 6 weeks at a dose of 25 mg/m^2 over 5-30 minutes Following the completion of doxorubin, etoposide 50 mg/m^2/day will be given orally for 21 days of each 28-day cycle (treatment can continue up to 24 cycles) Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA every 8 weeks (+/- 7 days) until 2 years have elapsed or disease progression, whichever comes first

Units	Counts
Participants	OG0005 OG0010

Title

Denominators

Categories

Title	Measurements
	OG0004

Primary

Arm A Only: Overall Survival (OS) as Measured by Number of Participants Alive at 5 Years

This outcome measure is for Arm A participants only.

Posted

Count of Participants

Participants

Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)

ID	Title	Description
OG000	Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression
OG001	Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Within 7 days of MLA (range 2-14 days) doxorubicin will be given intravenously on an outpatient basis weekly for 6 weeks at a dose of 25 mg/m^2 over 5-30 minutes Following the completion of doxorubin, etoposide 50 mg/m^2/day will be given orally for 21 days of each 28-day cycle (treatment can continue up to 24 cycles) Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA every 8 weeks (+/- 7 days) until 2 years have elapsed or disease progression, whichever comes first

Primary

Arm B Only: Number of Participants With Progression-free Survival (PFS)

PFS is followed from start of treatment to time of progression or death, whichever occurs first.

This outcome measure is for Arm B participants only.

Posted

Count of Participants

Participants

At 6 months

ID	Title	Description
OG000	Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression
OG001	Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Within 7 days of MLA (range 2-14 days) doxorubicin will be given intravenously on an outpatient basis weekly for 6 weeks at a dose of 25 mg/m^2 over 5-30 minutes Following the completion of doxorubin, etoposide 50 mg/m^2/day will be given orally for 21 days of each 28-day cycle (treatment can continue up to 24 cycles) Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA every 8 weeks (+/- 7 days) until 2 years have elapsed or disease progression, whichever comes first

Secondary

Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status

Score ranges from 100% to 10%. A higher score indicates that the patient has a more normal quality of life.

This data was not collected on the patient from Arm B.

Posted

Number

score on a scale

At 1 year post-MLA

ID	Title	Description
OG000	Patient 1: Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression
OG001	Patient 2: Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression

Secondary

Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)

Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA
Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first.
Neuron specific enolase is an enzyme involved in glycolysis, which is localized in neurons and axonal processes. Potentially, it escapes into the blood and CSF at the time of neural injury. Elevated serum NSE seemed to correlates with disruption in BBB following MLA and transient increase in BBB permeability.

The one participant in Arm B did not consent to any procedures past 12 months post-MLA. There are time points not included because either the NSE was not detected in the samples or the samples were not collected.

Posted

Number

ng/ml

Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B)

ID	Title	Description
OG000	Patient 1: Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression

Secondary

Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B

Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA
Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first.
S100b is a low-molecular-weight Calcium-binding protein primarily found in astrocytic glial cells of the CNS. It is secreted by astrocytes for neuroprotective and -trophic cellular functions in the CNS. Elevated serum values can be associated with temporal changes in BBB integrity following MLA.

The one participant in Arm B did not consent to any procedures past 12 months post-MLA. There are time points not included because either the S100B was not detected in the samples or the samples were not collected.

Posted

Number

pg/ml

Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B)

ID	Title	Description
OG000	Patient 1: Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression

Secondary

Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP

Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA
Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first.
The glial fibrillary acidic protein (GFAP) is a classic intermediate filament protein specific to astrocytes in the CNS. GFAP is characteristic of astrocyte- and neural stem cell-derived gliomas in CNS tumors and is used to identify malignancies of glial origin, such as astrocytomas and GBM. Serum GFAP values can be increased with temporal disruption of BBB post-MLA.

The one participant in Arm B did not consent to any procedures past 12 months post-MLA. There are time points not included because either the GFAP was not detected in the samples or the samples were not collected.

Posted

Number

ng/ml

Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B)

ID	Title	Description
OG000	Patient 1: Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression

Secondary

Correlation of MR Imaging With Peritumoral BBB Disruption

The linear regression model will used to investigate the correlation between MR imaging and peritumoral BBB disruption. To account for correlation among the repeated measures from the same patient, the longitudinal data will be analyzed with the use of linear generalized estimating equation (GEE). Whether the average measurements differ at the multiple time points will be evaluated through GEE model. Least-square means at each time points will be presented and standard errors will be calculated within the use of the GEE sandwich method when accounting for within-patient correlation.

Data was not collected for this outcome measure.

Posted

1 year from MLA

ID	Title	Description
OG000	Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression
OG001	Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)

Secondary

Predictive Value of the Peritumoral Permeability Score for Patient Outcome as Measured by PFS

Biomarkers with higher correlation coefficient (r approaching 1) will be given higher priority. 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 (as measured by 6 month PFS rate) to determine whether it has a predictive value.

Data was not collected for this outcome measure.

Posted

6 months

ID	Title	Description
OG000	Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression
OG001	Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Within 7 days of MLA (range 2-14 days) doxorubicin will be given intravenously on an outpatient basis weekly for 6 weeks at a dose of 25 mg/m^2 over 5-30 minutes Following the completion of doxorubin, etoposide 50 mg/m^2/day will be given orally for 21 days of each 28-day cycle (treatment can continue up to 24 cycles) Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA every 8 weeks (+/- 7 days) until 2 years have elapsed or disease progression, whichever comes first

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A (MRI-guided Laser Ablation)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA Every 12 weeks (+/- 7 days) for the first year or until disease progression	0	5	0	5	5	5
EG001	Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)	MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim. Within 7 days of MLA (range 2-14 days) doxorubicin will be given intravenously on an outpatient basis weekly for 6 weeks at a dose of 25 mg/m^2 over 5-30 minutes Following the completion of doxorubin, etoposide 50 mg/m^2/day will be given orally for 21 days of each 28-day cycle (treatment can continue up to 24 cycles) Participants will undergo DCE and DSC-MRI imaging at the following time points: no more than 3 weeks prior to MLA (OPTIONAL) within approximately 4 days after MLA 2-4 weeks after MLA every 8 weeks (+/- 7 days) until 2 years have elapsed or disease progression, whichever comes first	0	1	0	1	0	1

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fecal incontinence	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected5 at risk EG0010 affected1 at risk
Fatigue	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected5 at risk EG0010 affected1 at risk
Headache	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected5 at risk EG0010 affected1 at risk
Paresthesia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected5 at risk EG0010 affected1 at risk
Memory impairment	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected5 at risk EG0010 affected1 at risk
Confusion	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected5 at risk EG0010 affected1 at risk
Noise sensitive	Social circumstances	CTCAE (4.0)	Systematic Assessment	EG0001 affected5 at risk EG0010 affected1 at risk

The protocol stated that participants were to be followed for 5 years from participant registration or until death, whichever occurred first. The original consent that the participants signed stated that they would only be followed for 12 months after MLA. Once this issue was discovered, participants were contacted to be reconsented to be followed for 5 years; however, not all participants were able to be reconsented and that is why the results are late.

Certain Agreements

ID	Term
D005910	Glioma
D001254	Astrocytoma
D005909	Glioblastoma
D009837	Oligodendroglioma
D020339	Optic Nerve Glioma

Ancestor Terms

ID	Term
D018302	Neoplasms, Neuroepithelial
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009375	Neoplasms, Glandular and Epithelial
D009380	Neoplasms, Nerve Tissue
D019574	Optic Nerve Neoplasms
D003390	Cranial Nerve Neoplasms
D009423	Nervous System Neoplasms
D009371	Neoplasms by Site
D010524	Peripheral Nervous System Neoplasms
D003389	Cranial Nerve Diseases
D009422	Nervous System Diseases
D009901	Optic Nerve Diseases
D005128	Eye Diseases

ID	Term
D004317	Doxorubicin
D005047	Etoposide
C061400	etoposide phosphate
D000098543	Dynamic Contrast Enhanced Magnetic Resonance Imaging
D000098642	Perfusion Magnetic Resonance Imaging

Ancestor Terms

ID	Term
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D011034	Podophyllotoxin
D013764	Tetrahydronaphthalenes
D009281	Naphthalenes
D005960	Glucosides
D008279	Magnetic Resonance Imaging
D014054	Tomography
D003952	Diagnostic Imaging
D019937	Diagnostic Techniques and Procedures
D003933	Diagnosis

MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim.
Within 7 days of MLA (range 2-14 days) doxorubicin will be given intravenously on an outpatient basis weekly for 6 weeks at a dose of 25 mg/m^2 over 5-30 minutes
Following the completion of doxorubin, etoposide 50 mg/m^2/day will be given orally for 21 days of each 28-day cycle (treatment can continue up to 24 cycles)
Participants will undergo DCE and DSC-MRI imaging at the following time points:
- no more than 3 weeks prior to MLA (OPTIONAL)
- within approximately 4 days after MLA
- 2-4 weeks after MLA
- every 8 weeks (+/- 7 days) until 2 years have elapsed or disease progression, whichever comes first