Focused Ultrasound + Etoposide for Brain Tumor

Overseen By James H Garvin, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Columbia University

Must be taking: Oral etoposide

Must not be taking: Investigational drugs, Anticancer agents

Disqualifiers: Uncontrolled seizures, Pregnancy, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 16 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat brain tumors in children by combining focused ultrasound with the cancer drug etoposide (also known as Eposin, VP-16, or Vepesid). The aim is to temporarily open the blood-brain barrier—a natural defense that prevents substances from entering the brain—so the drug can better reach the tumor, potentially improving treatment effectiveness and reducing side effects. Children with progressive diffuse midline gliomas, a type of brain tumor, who show signs of worsening disease may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on another investigational drug or anti-cancer agents. You must also be on a stable dose of steroids and anti-seizure medication for at least one week before joining.

What prior data suggests that focused ultrasound with neuro-navigator-controlled sonication is safe for opening the blood brain barrier?

Research has shown that focused ultrasound (FUS) is a safe and non-invasive method to temporarily open the blood-brain barrier (BBB), aiding drugs in reaching brain tumors more effectively. Studies have demonstrated that FUS can safely open the BBB and enhance drug delivery without surgery, reducing risks such as infections or wound healing issues.

Regarding etoposide, research indicates that patients with brain tumors generally tolerate it well. One study noted that patients experienced few side effects. Etoposide targets specific enzymes in cancer cells, helping to halt their growth.

In this trial, researchers are combining FUS and etoposide to enhance drug delivery to brain tumors safely. Although this is an early-stage trial, previous research provides a positive outlook on the safety of both treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for brain tumors, which often rely on surgery, radiation, or intravenous chemotherapy, this new approach combines focused ultrasound with oral etoposide. Researchers are excited because the focused ultrasound can enhance drug delivery directly to the tumor, potentially increasing the effectiveness of the chemotherapy. The use of microbubbles and neuro-navigator-controlled sonication helps target the treatment precisely, minimizing damage to surrounding healthy tissue. This novel delivery method could lead to better outcomes with fewer side effects compared to traditional therapies.

What evidence suggests that focused ultrasound with etoposide is effective for brain tumors?

Research has shown that focused ultrasound (FUS) can temporarily open the blood-brain barrier (BBB), helping drugs reach brain tumors more effectively and potentially improving treatment outcomes. Studies have found that combining ultrasound with chemotherapy enhances drug delivery to tumors. In this trial, all participants will receive focused ultrasound treatment followed by oral etoposide. Etoposide, a chemotherapy drug, targets brain tumors by blocking an enzyme that aids cancer cells in repairing their DNA. In some cases of aggressive brain tumors, patients treated with etoposide have lived longer. The combination of FUS and etoposide aims to enhance the drug's effectiveness and possibly improve outcomes for patients with diffuse midline gliomas. ^{3 5 6 7 8}

Who Is on the Research Team?

James H Garvin, MD, PhD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

Children and young adults aged 4-21 with a specific brain tumor called Diffuse Midline Glioma, involving the pons or thalami, can join this trial. They must have a certain level of physical ability (Lansky or Karnofsky score ≥60), proper organ function, and be off other cancer treatments for a set time. Those who've had etoposide before, are pregnant/breastfeeding, have uncontrolled seizures or infections, heart issues, bleeding disorders, metal implants/electrical devices in body cannot participate.

Inclusion Criteria

Subject able to give consent

I am between 4 and 21 years old.

My liver tests are within normal limits.

Exclusion Criteria

Subjects unable to tolerate study procedures and/or anesthesia based on the opinion of the principal investigator

Pregnancy or Breast-Feeding

I have been treated with etoposide before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive focused ultrasound (FUS) treatment with microbubbles and neuro-navigator-controlled sonication, concurrent with oral etoposide administration

Up to 16 weeks

Up to 3 visits per week during the first 2 weeks of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, including MRI and other radiological evidence to show successful BBB opening and closing

Up to 3 months

Monthly follow-up phone calls

What Are the Treatments Tested in This Trial?

Interventions

• Etoposide
• Focused ultrasound with neuro-navigator-controlled sonication

Trial Overview The study is testing if focused ultrasound (FUS) can safely open the blood-brain barrier to let more of the drug etoposide reach brain tumors in children with progressive diffuse midline gliomas. FUS uses microbubbles and sound waves guided by neuro-navigation to target areas around the tumor while giving oral etoposide.

How Is the Trial Designed?

Group I: Focused ultrasound using oral etoposide Experimental Treatment 2 Interventions

All patients enrolled in the study will be treated with oral etoposide after receiving focused ultrasound (FUS) treatment with microbubbles and neuro-navigator-controlled sonication.

Etoposide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Etoposide for:

• Testicular cancer
• Small cell lung cancer
• Non-Hodgkin lymphoma
• Acute myeloid leukemia

Approved in European Union as Etoposide for:

• Testicular cancer
• Small cell lung cancer
• Non-Hodgkin lymphoma
• Acute myeloid leukemia

Approved in Canada as Etoposide for:

• Testicular cancer
• Small cell lung cancer
• Non-Hodgkin lymphoma
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Cheng-Chia (Fred) Wu

Lead Sponsor

Trials

2

Recruited

10+

Focused Ultrasound Foundation

Collaborator

Trials

18

Recruited

460+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.1984.2.5.432

Etoposide (VP-16-213) in malignant brain tumors Overall median survival from the start of VP-16-213 was 4.5 months (range, 1 ... Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7271709/

Temozolomide and oral etoposide in children with recurrent ... Etoposide (VP-16), an inhibitor of nuclear enzyme deoxyribonucleic acid (DNA)-topoisomerase II, has shown activity in brain tumors.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8699237/

Phase II study of prolonged oral therapy with etoposide ... Median time to tumor progression (TTP) was 8.8 weeks for all evaluable patients, 8.6 weeks for those treated at first progression and 8.4 weeks for those ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/027753798890243X

Treatment of brain metastases of lung cancer with high ... To study the efficacy of etoposide in brain metastases of lung carcinoma, etoposide was given during 3 consecutive days. The total dose of 1500 mg/m2 was ...

5. ar.iiarjournals.org ar.iiarjournals.org/content/33/8/3307

Etoposide Improves Survival in High-grade Glioma: A Meta ... Results: Patient cohorts treated with etoposide had significant improvement in mOS (15.66 months vs. 13.27 months, p=0.026, 49 vs. 795 cohorts) and significant ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/6726296/

Etoposide (VP-16-213) in malignant brain tumors Overall, treatment was well tolerated. In 10 patients concomitant plasma and cerebrospinal fluid samples were evaluated with a high-performance liquid ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090301907009202

Pilot trial of the rate of response, safety, and tolerability ... The aim of this study was to determine the response and toxicity of patients with recurrent or treatment-induced brain tumors to TMZ and oral VP-16.

8. link.springer.com link.springer.com/article/10.1007/s00381-023-05872-w

Evaluating the efficacy and safety of single-agent ... Intra-CSF etoposide treatment has shown to increase both overall and progression-free survival significantly, whilst having few side effects and maintaining a ...