Optune System for Pediatric Brain Cancer

Not currently recruiting at 15 trial locations

Overseen By Emily Atwood

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Pediatric Brain Tumor Consortium

Must not be taking: Anticancer drugs, Investigational drugs

Disqualifiers: Other malignancy, Cardiac disorder, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the Optune device, a wearable treatment system, to evaluate its effectiveness and safety for children with certain brain cancers. The trial consists of two parts: one for children with advanced supratentorial brain tumors, such as high-grade glioma or ependymoma, that recur, and another for newly diagnosed diffuse intrinsic pontine glioma (DIPG). Children with these specific brain tumors who can use the Optune device for most of the day might be suitable candidates for this study.

As an unphased trial, this study provides a unique opportunity to explore a new treatment option for challenging brain cancers.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any other anticancer or investigational drug therapy. If you are on corticosteroids, the dose must be stable or decreasing for at least 5 days before enrollment for Stratum 1. For Stratum 2, there are no specific requirements for corticosteroid dosing.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on corticosteroids, the dose must be stable or decreasing for at least 5 days before joining the trial for Stratum 1. For Stratum 2, there are no specific requirements for corticosteroid dosing.

What prior data suggests that the Optune device is safe for pediatric brain cancer patients?

Research shows that the Optune System, which uses small electrical fields to stop cancer cells from growing, is generally easy for patients to handle. Studies have found that this treatment is already approved for adults with certain brain cancers and has not caused any new safety issues. Most patients report only mild side effects, with skin irritation being the most common. This suggests that while some discomfort may occur, serious problems are rare. For children, this device remains under testing, but information from adult use aids in understanding its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Optune System for pediatric brain cancer because it uses Tumor Treating Fields (TTFields), an innovative method that targets cancer cells by disrupting their division. Unlike the standard treatments like chemotherapy and radiation, which can damage healthy tissues, TTFields specifically focuses on cancer cells, potentially reducing side effects. This non-invasive approach offers a new way to manage aggressive brain tumors like DIPG and high-grade gliomas, providing hope for improved outcomes where traditional methods have limited success.

What evidence suggests that the Optune System is effective for pediatric brain cancer?

Studies have shown that the Optune System can help treat certain brain cancers. This device uses gentle electric fields, known as Tumor Treating Fields (TTFields), to disrupt cancer cell growth. Research suggests these fields may slow or stop cancer cells from growing in the brain. In this trial, one arm will test the Optune System in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) alongside focal radiation therapy. Another arm will evaluate the Optune System in children with recurrent or progressive high-grade glioma or ependymoma. This method is being tested to determine its effectiveness in managing these difficult-to-treat cancers. ^{2 5 6 7 8}

Who Is on the Research Team?

Stewart Goldman, MD

Principal Investigator

Phoenix Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children with high-grade glioma or ependymoma (5-21 years old) and those with newly diagnosed DIPG (3-21 years old). Participants must have stable neurological deficits, measurable disease, and meet specific organ function criteria. They should not have received certain prior treatments within specified time frames and must be willing to use the Optune device extensively.

Inclusion Criteria

Disease Status: Patients must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two planes. Stratum 1: Disease must be located primarily in the supratentorial region. Patients with significant disease that is metastatic outside of the supratentorial region are ineligible. Stratum 2: Disease must be located primarily in the pons.

My steroid dose has been stable or decreasing for the last 5 days.

I am willing to use the Optune device for the required hours and keep my head shaved.

Exclusion Criteria

Cardiac Disorder: Patients with pacemaker, defibrillator, or documented significant arrhythmia are not allowed.

Systemic Illness: Patients with any clinically significant unrelated systemic illness that, in the opinion of the investigator, would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity, or would interfere with the study procedures or results.

Skull Defects: Patients with major skull defects (such as missing bone without replacement) are not eligible.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Optune therapy for at least 18 hours a day, with a recommendation of 22 hours/day for at least 23 days in a 28-day cycle. Treatment may continue up to 26 cycles in Stratum 1 and up to 5 years in Stratum 2.

Up to 5 years

Concurrent Optune and Radiation Therapy

Participants in Stratum 2 receive concurrent Optune therapy and standard focal radiation therapy to evaluate safety, tolerability, and efficacy.

49 days

Follow-up

Participants are monitored for safety, effectiveness, and unexpected later developing toxicities after treatment. Follow-up lasts for 2 years in Stratum 1 and 3 years in Stratum 2.

2-3 years

What Are the Treatments Tested in This Trial?

Interventions

• Optune System

Trial Overview The study tests the Optune device's safety and effectiveness in two groups: one with supratentorial high-grade glioma or ependymoma using Optune alone, another with newly diagnosed DIPG using both Optune and radiation therapy. The goal is to see if this treatment can help manage these brain tumors in children.

How Is the Trial Designed?

Group I: Treatment (Optune System) Experimental Treatment 1 Intervention

Patients must have a histologically confirmed diagnosis of supratentorial high-grade glioma or supratentorial ependymoma that is recurrent, progressive or refractory. All patients will use the study device Optune System (Tumor Treating Fields, TTFields).

Group II: Treatment (Concurrent Optune/focal radiation therapy followed by Optune-only therapy) Experimental Treatment 1 Intervention

Patients must have newly diagnosed DIPG (a typical DIPG on MR imaging, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, without histologic confirmation; atypical DIPG undergoing a biopsy and the tumor is a diffuse glioma WHO Grade II-IV with OR without H3 K27M mutation; or pontine lesions that do not meet these MR imaging criteria with histologically confirmed diffuse glioma WHO Grade II-IV with H3 K27M- mutation). This arm will consist of two parts: a phase I component to evaluate the safety and tolerability of concurrent Optune and RT, and a phase II component to evaluate the feasibility of concurrent Optune and RT and the efficacy associated with this approach compared to historical controls.

Optune System is already approved in United States, European Union for the following indications:

Approved in United States as Optune for:

• Glioblastoma multiforme (GBM)
• Malignant pleural mesothelioma (MPM)
• Non-small cell lung cancer (mNSCLC)

Approved in European Union as Optune for:

• Glioblastoma multiforme (GBM)

Who Is Running the Clinical Trial?

Pediatric Brain Tumor Consortium

Lead Sponsor

Trials

38

Recruited

1,600+

NovoCure Ltd.

Industry Sponsor

Trials

64

Recruited

6,100+

Ashley Cordova

NovoCure Ltd.

Chief Executive Officer

Bachelor of Science in Material Engineering from Ben-Gurion University of the Negev, Israel

Uri Weinberg

NovoCure Ltd.

Chief Medical Officer since 2020

MD from an unspecified institution

American Lebanese Syrian Associated Charities (ALSAC)

Collaborator

Trials

9

Recruited

670+

American Lebanese Syrian Associated Charities

Collaborator

Trials

9

Recruited

670+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Recent clinical trials highlight the importance of combining new drugs with radiotherapy in treating pediatric brain tumors, focusing on both survival rates and quality of life.

Specific studies, such as the SIOP/UKCCSG PNET-3 trial, have shown that pre-irradiation chemotherapy can be more effective than radiotherapy alone for medulloblastoma, while the French M-SFOP 98 protocol suggests that hyper-fractionated radiotherapy may reduce early relapses and preserve intellectual function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A literature review of the recent radiotherapy clinical trials in pediatric brain tumors. Skowrońska-Gardas, A.[2019]

Nimotuzumab, a monoclonal antibody targeting the EGFR, was well tolerated in a study of 22 pediatric patients with progressive or recurrent brain tumors, showing a broad safety profile even with prolonged use.

The treatment resulted in disease control for 64% of patients, with notable survival rates of 82% at 6 months and 64% at 1 year, along with improvements in neurological functions and overall health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with nimotuzumab in cuban pediatric patients with brain tumors, 2005 to 2007. Saurez, G., Cabanas, R., Zaldívar, M., et al.[2021]

The humanized anti-CD47 antibody, Hu5F9-G4, shows promising therapeutic efficacy against various aggressive pediatric brain tumors, including medulloblastoma and glioblastoma, in both laboratory and animal models.

Hu5F9-G4 appears to be safe, as it demonstrated minimal activity against normal human neural cells, suggesting it could effectively target tumor cells while sparing healthy tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors. Gholamin, S., Mitra, SS., Feroze, AH., et al.[2021]

The NABTT CNS Consortium has made significant strides in understanding drug interactions and treatment strategies for high-grade astrocytomas, including discovering important interactions between anticonvulsants and cancer drugs.

Their research has led to the identification of effective agents like paclitaxel and 9-aminocamptothecin for glioblastoma multiforme, and the development of new clinical trial protocols aimed at improving patient outcomes and standardizing research efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium: Organization, Objectives, and Activities. Grossman, SA., Fisher, JD., Piantadosi, S., et al.[2019]

In a phase II trial involving 65 pediatric patients with progressive/recurrent low-grade gliomas, everolimus demonstrated a 6-month progression-free survival (PFS) rate of 67.4% and a median PFS of 11.1 months, indicating its efficacy as a treatment option.

The study identified rare/novel KIAA1549::BRAF fusion breakpoints as potential biomarkers for poor clinical outcomes, suggesting that these genetic alterations could help predict disease progression in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus for Children With Recurrent or Progressive Low-Grade Glioma: Results From the Phase II PNOC001 Trial. Haas-Kogan, DA., Aboian, MS., Minturn, JE., et al.[2023]

A new patient-derived orthotopic xenograft (PDOX) model of posterior fossa A (PFA) ependymoma was established, showing that the model retains key molecular and histological features of the original patient tumor, which is crucial for testing new treatments.

Despite the aggressive nature of PFA ependymomas, the PDOX model faced challenges in being maintained beyond two passages in vivo, indicating the difficulties in developing stable laboratory models for this type of pediatric brain cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo loss of tumorigenicity in a patient-derived orthotopic xenograft mouse model of ependymoma. Whitehouse, JP., Hii, H., Mayoh, C., et al.[2023]

Molecular analysis of a pediatric high-grade glioma revealed actionable mutations and amplifications, including TP53 and MYCN, which guided the selection of targeted therapies.

In vivo testing in a patient-derived xenograft (PDX) model showed that the mTOR inhibitor temsirolimus and the PLK1 inhibitor BI2536 significantly improved survival compared to standard therapies, highlighting the potential of precision medicine in treating pediatric brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integration of genomics, high throughput drug screening, and personalized xenograft models as a novel precision medicine paradigm for high risk pediatric cancer. Tsoli, M., Wadham, C., Pinese, M., et al.[2020]

Survival rates for pediatric central nervous system tumors have significantly improved due to advancements in neuroimaging, surgery, radiation, and medical treatments, highlighting the effectiveness of modern approaches.

The management of pediatric brain tumors now requires a multidisciplinary team, leading to the development of pediatric neuro-oncologists who specialize in this complex field, ensuring better care and follow-up for affected children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the management of pediatric central nervous system tumors. Abdullah, S., Qaddoumi, I., Bouffet, E.[2008]

Precision oncology, which tailors cancer treatment based on the genomic profile of a patient's tumor, is showing promise in effectively treating some children with cancer, supported by recent clinical trials and case reports.

An emerging regulatory framework is helping to speed up clinical trials for pediatric cancer treatments, while also addressing unique challenges in drug development for young patients, particularly for cancers driven by hard-to-target proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ushering in the next generation of precision trials for pediatric cancer. DuBois, SG., Corson, LB., Stegmaier, K., et al.[2020]

Novel biologic agents are being tested in pediatric clinical trials for treating brain tumors, showing promise for better central nervous system penetration and lower toxicity compared to traditional chemotherapy and radiotherapy.

These biologic agents may offer equal or greater efficacy in infants and younger children while potentially reducing harmful side effects on the developing brain, highlighting a shift towards more targeted therapies in pediatric oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologically targeted therapeutics in pediatric brain tumors. Nageswara Rao, AA., Scafidi, J., Wells, EM., et al.[2021]

The Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI) was developed to provide a reliable and valid measure of treatment intensity for childhood CNS tumors, addressing the complexities of treatment protocols.

The PNORTI demonstrated high inter-rater reliability and agreement among experts, indicating it can effectively classify treatment intensity levels, which is crucial for research on childhood cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of the Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI). Hocking, MC., Hobbie, W., Fisher, MJ.[2019]

Vinblastine, given weekly for 70 weeks, is well tolerated and shows promising efficacy in therapy-naïve children with pediatric low-grade glioma (PLGG), achieving a 94.4% overall survival rate and 53.2% progression-free survival rate.

The treatment resulted in disease stabilization in 87% of patients, with visual improvements in 20% of those with optic pathway glioma, and patients with neurofibromatosis type 1 (NF1) had significantly better progression-free survival compared to those without NF1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Weekly Vinblastine for Chemotherapy-Naïve Children With Progressive Low-Grade Glioma: A Canadian Pediatric Brain Tumor Consortium Study. Lassaletta, A., Scheinemann, K., Zelcer, SM., et al.[2018]

In a study involving 32 pediatric patients with BRAF V600-mutant low-grade glioma, dabrafenib showed a 44% objective response rate and an impressive 85% one-year progression-free survival rate, indicating its effectiveness in treating this type of brain tumor.

The treatment was generally well-tolerated, with 91% of patients experiencing treatment-related adverse events, primarily fatigue, and only 28% experiencing severe (grade 3/4) side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dabrafenib in Pediatric Patients with BRAF V600 Mutation-Positive Relapsed or Refractory Low-Grade Glioma: Results from a Phase I/IIa Study. Hargrave, DR., Bouffet, E., Tabori, U., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03033992?term=AREA%5BConditionSearch%5D(Diffuse%20intrinsic%20pontine%20glioma%20OR%20%22DIPG%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=9

Optune for Children With High-Grade Glioma or ... This is a multicenter trial of the Optune device to examine the feasibility and to describe the device-related toxicity in children with ...

2. withpower.com withpower.com/trial/phase-ependymoma-3-2017-9675a

Optune System for Pediatric Brain Cancer · Info for Participants Trial Overview The study tests the Optune device's safety and effectiveness in two groups: one with supratentorial high-grade glioma or ependymoma using Optune ...

3. stjude.org stjude.org/care-treatment/clinical-trials/pbtc48-pediatric-brain-tumor.html

PBTC48: Optune for High-Grade Glioma, Ependymoma, or ... The medical device is called Optune. It works by sending mild electric fields to the brain. These electric fields may slow or stop cancer cells from growing.

4. clinicaltrial.be clinicaltrial.be/en/details/9348?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Optune for Children With High-Grade Glioma or ... The Optune System produces alternating electrical fields, called tumor treatment fields (TTFields) by means of 4 transducer arrays placed on the ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10150168/

Safety and efficacy of tumour-treating fields (TTFields) therapy ... Here, we report post-approval data of tumour-treating fields therapy in Japanese patients with newly diagnosed glioblastoma. Methods.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11269345/

Global post‑marketing safety surveillance of Tumor Treating ... TTFields therapy is approved for recurrent glioblastoma (rGBM), and newly-diagnosed (nd) GBM (with concomitant temozolomide for ndGBM; US), and ...

7. aetna.com aetna.com/cpb/medical/data/800_899/0827.html

Electric Tumor Treatment Fields - Medical Clinical Policy ... The FDA-approved indication for use is: "The NovoTTF-100A System is intended as treatment for adult patients (22 years of age or older) with histologically ...

8. accessdata.fda.gov accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=p100034s013

Premarket Approval (PMA) - FDA OPTUNE (FORMERLY THE NOVOTTF-100A SYSTEM). Generic Name, Stimulator, low electric field, tumor treatment. Applicant, Novocure GmbH. Neuhofstrasse 21. Baar 6340.