MRI-Guided Laser Ablation + Chemotherapy for Brain Cancer

Recruiting in Palo Alto (17 mi)

Overseen byAndrew Cluster, M.D.

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Washington University School of Medicine

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Research Team

Andrew Cluster, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for children and young adults aged 3 to 21 with certain types of brain tumors, including various grades of gliomas. Participants must have a performance status indicating they can carry out daily activities (≥60%), adequate heart, liver, and bone marrow function, and not exceed prior anthracycline therapy limits. Pregnant individuals or those unable to undergo MRI are excluded.

Inclusion Criteria

I am between 3 and 21 years old with a brain tumor suitable for surgery and can do most activities.

ARM B: Recurrent pediatric brain tumors determined candidates for MLA as determined by the treating neurosurgeon, Unequivocal evidence of tumor progression by MRI, 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, Recurrent lesions appropriate for MLA, Age 3 to ≤ 21, Karnofsky/Lansky performance status ≥ 60%, Adequate cardiac function, Prior anthracycline therapy not exceeding 200 mg/m^2 total cumulative dose, Adequate bone marrow and hepatic function criteria met within 7 days of MLA, Recovery from toxic effects of prior therapy to no more than grade 1 toxicity, At least 4 weeks from other prior cytotoxic chemotherapy, Agreement to use adequate contraception, Ability to understand and sign an IRB approved written informed consent document

Exclusion Criteria

ARM A: Currently receiving or scheduled to receive 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, Pregnancy or breastfeeding, Inability to undergo MRI, 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 certain anthracyclines, More than 2 prior relapses, Currently receiving other investigational agents for the relapsed tumor, Multi-focal or metastatic disease, History of allergic reactions to compounds similar to study agents, Uncontrolled intercurrent illness, Pregnancy or breastfeeding, Inability to undergo MRI, Known history of HIV or autoimmune diseases requiring immunosuppressant drugs

Treatment Details

Interventions

Doxorubicin (Chemotherapy)
Etoposide (Chemotherapy)
MRI-guided laser ablation (Procedure)

Trial OverviewThe study tests the timing of maximal blood-brain barrier disruption using MRI-guided laser ablation followed by chemotherapy in pediatric patients. The goal is to optimize treatment delivery while minimizing systemic side effects and distinguishing between tumor progression and treatment effects.

Participant Groups

2Treatment groups

Experimental Treatment

Group I: Arm B (MRI-guided laser ablation, doxorubicin, etoposide)Experimental Treatment5 Interventions

* 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

Group II: Arm A (MRI-guided laser ablation)Experimental Treatment3 Interventions