A Pilot Study of Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Arm B Only: Number of Participants With Progression-free Survival (PFS)
研究概览
简要总结
By employing a combination of advanced MRI techniques and correlative serum biomarkers of blood brain barrier (BBB) disruption, the investigators plan to develop a powerful, first of its kind clinical algorithm in pediatrics whereby the investigators can measure and identify the window of maximal BBB disruption post MLA to 1) allow for an alternative to surgery in incompletely resected tumors, 2) allow for optimal chemotherapeutic dosing to achieve the greatest benefits and the least systemic side effects and 3) distinguish subsequent tumor progression from long-term MLA treatment effects. Preliminary data in adult imaging studies have shown that the BBB disruption lasts for several weeks following treatment before returning to a low baseline. This pilot therapeutic study will provide preliminary validation in pediatric patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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%
- •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).
排除标准
- •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.
- •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.
研究组 & 干预措施
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
干预措施: MRI-guided laser ablation (Device)
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
干预措施: Dynamic contrast-enhanced (DCE) MRI (Device)
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
干预措施: Dynamic susceptibility contrast (DSC) MRI (Device)
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
干预措施: MRI-guided laser ablation (Device)
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
干预措施: Doxorubicin (Drug)
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
干预措施: Etoposide (Drug)
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
干预措施: Dynamic contrast-enhanced (DCE) MRI (Device)
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
干预措施: Dynamic susceptibility contrast (DSC) MRI (Device)
结局指标
主要结局
Arm B Only: Number of Participants With Progression-free Survival (PFS)
时间窗: At 6 months
PFS is followed from start of treatment to time of progression or death, whichever occurs first.
Arm A Only: Number of Participants With Progression-free Survival (PFS)
时间窗: Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)
PFS is followed from start of treatment to time of progression or death, whichever occurs first.
Arm A Only: Overall Survival (OS) as Measured by Number of Participants Alive at 5 Years
时间窗: Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)
次要结局
- Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status(At 1 year post-MLA)
- Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)(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))
- Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP(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))
- Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B(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))
- Correlation of MR Imaging With Peritumoral BBB Disruption(1 year from MLA)
- Predictive Value of the Peritumoral Permeability Score for Patient Outcome as Measured by PFS(6 months)