Trial Outcomes & Findings for Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors (NCT NCT02372409)
NCT ID: NCT02372409
Last Updated: 2024-11-01
Results Overview
PFS is followed from start of treatment to time of progression or death, whichever occurs first.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
6 participants
Primary outcome timeframe
Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)
Results posted on
2024-11-01
Participant Flow
Participant milestones
| Measure |
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
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
1
|
|
Overall Study
COMPLETED
|
3
|
0
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
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
|
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
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Disease progression
|
1
|
1
|
Baseline Characteristics
Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors
Baseline characteristics by cohort
| Measure |
Arm A (MRI-guided Laser Ablation)
n=5 Participants
* 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
|
Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)
n=1 Participants
* 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
|
Total
n=6 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
11 years
n=5 Participants
|
12 years
n=7 Participants
|
11.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
1 participants
n=7 Participants
|
6 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)Population: This outcome measure is for Arm A participants only.
PFS is followed from start of treatment to time of progression or death, whichever occurs first.
Outcome measures
| Measure |
Patient 1: 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
|
Patient 1: Arm A (MRI-guided Laser Ablation)
n=5 Participants
* 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
|
Patient 4: 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
|
Patient 3: 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
|
Patient 5: 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
|
Patient 6: 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
|
|---|---|---|---|---|---|---|
|
Arm A Only: Number of Participants With Progression-free Survival (PFS)
|
—
|
4 Participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)Population: This outcome measure is for Arm A participants only.
Outcome measures
| Measure |
Patient 1: 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
|
Patient 1: Arm A (MRI-guided Laser Ablation)
n=5 Participants
* 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
|
Patient 4: 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
|
Patient 3: 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
|
Patient 5: 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
|
Patient 6: 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
|
|---|---|---|---|---|---|---|
|
Arm A Only: Overall Survival (OS) as Measured by Number of Participants Alive at 5 Years
|
—
|
5 Participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: At 6 monthsPopulation: This outcome measure is for Arm B participants only.
PFS is followed from start of treatment to time of progression or death, whichever occurs first.
Outcome measures
| Measure |
Patient 1: 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
|
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
|
Patient 4: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 3: 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
|
Patient 5: 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
|
Patient 6: 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
|
|---|---|---|---|---|---|---|
|
Arm B Only: Number of Participants With Progression-free Survival (PFS)
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At 1 year post-MLAPopulation: This data was not collected on the patient from Arm B.
Score ranges from 100% to 10%. A higher score indicates that the patient has a more normal quality of life.
Outcome measures
| Measure |
Patient 1: 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
|
Patient 1: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 4: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 3: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 5: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 6: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
|---|---|---|---|---|---|---|
|
Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status
Baseline
|
—
|
90 score on a scale
|
100 score on a scale
|
80 score on a scale
|
100 score on a scale
|
100 score on a scale
|
|
Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status
1 year post-MLA
|
—
|
90 score on a scale
|
100 score on a scale
|
80 score on a scale
|
100 score on a scale
|
100 score on a scale
|
SECONDARY outcome
Timeframe: 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)Population: 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.
* 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.
Outcome measures
| Measure |
Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)
n=1 Participants
* 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
|
Patient 1: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 4: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 3: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 5: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 6: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
|---|---|---|---|---|---|---|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
48 weeks
|
—
|
15.4708 ng/ml
|
35.6507 ng/ml
|
—
|
25.8530 ng/ml
|
5.9343 ng/ml
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
Baseline
|
11.5114 ng/ml
|
29.0219 ng/ml
|
58.3406 ng/ml
|
3.1823 ng/ml
|
13.1819 ng/ml
|
7.5534 ng/ml
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
Day 3
|
18.5711 ng/ml
|
47.2666 ng/ml
|
26.7537 ng/ml
|
6.0443 ng/ml
|
33.8034 ng/ml
|
17.4680 ng/ml
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
1 week
|
11.5909 ng/ml
|
—
|
—
|
—
|
—
|
—
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
2 week
|
8.6069 ng/ml
|
—
|
—
|
—
|
—
|
—
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
2-4 weeks
|
—
|
12.0186 ng/ml
|
53.2519 ng/ml
|
5.4452 ng/ml
|
11.4998 ng/ml
|
9.3916 ng/ml
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
4 week
|
5.7440 ng/ml
|
—
|
—
|
—
|
—
|
—
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
12 weeks
|
—
|
105.7828 ng/ml
|
15.1011 ng/ml
|
7.5436 ng/ml
|
206.8570 ng/ml
|
13.5989 ng/ml
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
14 weeks
|
6.1692 ng/ml
|
—
|
—
|
—
|
—
|
—
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
24 weeks
|
—
|
19.1706 ng/ml
|
7.8464 ng/ml
|
3.8632 ng/ml
|
5.5086 ng/ml
|
13.8210 ng/ml
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
36 weeks
|
—
|
22.8186 ng/ml
|
7.9655 ng/ml
|
—
|
10.0722 ng/ml
|
5.9368 ng/ml
|
SECONDARY outcome
Timeframe: 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)Population: 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.
* 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.
Outcome measures
| Measure |
Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)
n=1 Participants
* 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
|
Patient 1: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 4: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 3: 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
|
Patient 5: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 6: 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
|
|---|---|---|---|---|---|---|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B
Baseline
|
—
|
—
|
79.74 pg/ml
|
—
|
—
|
—
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B
Day 3
|
35.90 pg/ml
|
39.90 pg/ml
|
58.86 pg/ml
|
—
|
—
|
—
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B
2-4 weeks
|
—
|
—
|
55.74 pg/ml
|
—
|
—
|
—
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B
12 weeks
|
—
|
156.00 pg/ml
|
59.78 pg/ml
|
—
|
239.13 pg/ml
|
—
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B
24 weeks
|
—
|
—
|
65.91 pg/ml
|
—
|
—
|
—
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B
36 weeks
|
—
|
—
|
55.66 pg/ml
|
—
|
—
|
—
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B
48 weeks
|
—
|
—
|
79.11 pg/ml
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: 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.
* 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.
Outcome measures
| Measure |
Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)
n=1 Participants
* 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
|
Patient 1: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 4: 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
|
Patient 3: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 5: Arm A (MRI-guided Laser Ablation)
n=1 Participants
* 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
|
Patient 6: 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
|
|---|---|---|---|---|---|---|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP
Day 3
|
5.6051762 ng/ml
|
4.7370968 ng/ml
|
—
|
1.6146649 ng/ml
|
0.2225989 ng/ml
|
—
|
|
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP
2-4 weeks
|
—
|
0.0652591 ng/ml
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 year from MLAPopulation: Data was not collected for this outcome measure.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 monthsPopulation: Data was not collected for this outcome measure.
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.
Outcome measures
Outcome data not reported
Adverse Events
Arm A (MRI-guided Laser Ablation)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm A (MRI-guided Laser Ablation)
n=5 participants at risk
* 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
|
Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)
n=1 participants at risk
* 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
|
|---|---|---|
|
Gastrointestinal disorders
Fecal incontinence
|
20.0%
1/5 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
0.00%
0/1 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
|
General disorders
Fatigue
|
20.0%
1/5 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
0.00%
0/1 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
|
Nervous system disorders
Headache
|
20.0%
1/5 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
0.00%
0/1 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
|
Nervous system disorders
Paresthesia
|
20.0%
1/5 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
0.00%
0/1 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
|
Nervous system disorders
Memory impairment
|
20.0%
1/5 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
0.00%
0/1 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
|
Psychiatric disorders
Confusion
|
20.0%
1/5 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
0.00%
0/1 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
|
Social circumstances
Noise sensitive
|
20.0%
1/5 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
0.00%
0/1 • -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).
For patients in Arm A, adverse events (of any grade) considered possibly, probably, or definitely related to the MLA need be reported. Adverse events that are possibly, probably, or definitely related to study procedures will be followed until resolution or stabilization of the event. "Stabilization" is defined as remaining at a consistent CTCAE version 4.0 grade of the event for two consecutive assessments. For Arm B, all grade 3 and higher events regardless of attribution are to be reported.
|
Additional Information
Andrew Cluster, M.D.
Washington University School of Medicine
Phone: 314-454-6018
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place