Optune System for Pediatric Brain Cancer
Recruiting in Palo Alto (17 mi)
+13 other locations
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Waitlist Available
Sponsor: Pediatric Brain Tumor Consortium
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This is a multicenter trial of the Optune device to examine the feasibility and to describe the device-related toxicity in children with supratentorial high grade glioma (HGG) or ependymoma (Stratum 1) and to examine the feasibility and efficacy of concurrent Optune and standard focal radiation therapy (RT) in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) (Stratum 2).
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.
What data supports the idea that Optune System for Pediatric Brain Cancer is an effective treatment?
The available research does not provide specific data on the effectiveness of the Optune System for Pediatric Brain Cancer. Instead, it discusses other treatments and approaches for pediatric brain tumors, such as biologic agents and precision medicine, which may offer better outcomes and fewer side effects compared to traditional methods like chemotherapy and radiation. However, without direct data on the Optune System, we cannot conclude its effectiveness for pediatric brain cancer based on the provided information.
12345What safety data is available for the Optune System in treating pediatric brain cancer?
The provided research does not contain specific safety data for the Optune System, NovoTTF-100A System, or Optune Lua in treating pediatric brain cancer. The studies focus on other treatments like vinblastine, anti-CD47 antibodies, dabrafenib, and nimotuzumab, which have shown varying safety profiles and efficacy in pediatric brain tumors. Further research specifically on the Optune System is needed to provide relevant safety data.
46789Is the Optune System a promising treatment for pediatric brain cancer?
Yes, the Optune System is a promising treatment for pediatric brain cancer because it represents a new approach that could potentially improve outcomes and reduce side effects compared to traditional methods like surgery, chemotherapy, and radiation. It is part of a broader trend of developing treatments that target specific cancer pathways, which may be more effective and less harmful to the developing brain.
110111213Eligibility Criteria
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.
+8 more
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.
+8 more
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Treatment (Optune System)Experimental Treatment1 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 Treatment1 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Children's Healthcare of AtlantaAtlanta, GA
Saint Jude Children's Research HospitalMemphis, TN
Children's Hospital of Pittsburgh of UPMCPittsburgh, PA
Children's Hospital of ColoradoAurora, CO
More Trial Locations
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Who Is Running the Clinical Trial?
Pediatric Brain Tumor ConsortiumLead Sponsor
NovoCure Ltd.Industry Sponsor
American Lebanese Syrian Associated Charities (ALSAC)Collaborator
American Lebanese Syrian Associated CharitiesCollaborator
National Cancer Institute (NCI)Collaborator
References
Biologically targeted therapeutics in pediatric brain tumors. [2021]Pediatric brain tumors are often difficult to cure and involve significant morbidity when treated with traditional treatment modalities, including neurosurgery, conventional chemotherapy, and radiotherapy. During the past two decades, a clearer understanding of tumorigenesis, molecular growth pathways, and immune mechanisms in the pathogenesis of cancer has opened up promising avenues for therapy. Pediatric clinical trials with novel biologic agents are underway to treat various pediatric brain tumors, including high and low grade gliomas and embryonal tumors. As the therapeutic potential of these agents undergoes evaluation, their toxicity profiles are also becoming better understood. These agents have potentially better central nervous system penetration and lower toxicity profiles compared with conventional chemotherapy. In infants and younger children, biologic agents may prove to be of equal or greater efficacy compared with traditional chemotherapy and radiation therapy, and may reduce the deleterious side effects of traditional therapeutics on the developing brain. Molecular pathways implicated in pediatric brain tumors, agents that target these pathways, and current clinical trials are reviewed. Associated neurologic toxicities will be discussed subsequently. Considerable work is needed to establish the efficacy of these agents alone and in combination, but pediatric neurologists should be aware of these agents and their rationale.
Integration of genomics, high throughput drug screening, and personalized xenograft models as a novel precision medicine paradigm for high risk pediatric cancer. [2020]Pediatric high grade gliomas (HGG) are primary brain malignancies that result in significant morbidity and mortality. One of the challenges in their treatment is inter- and intra-tumoral heterogeneity. Precision medicine approaches have the potential to enhance diagnostic, prognostic and/or therapeutic information. In this case study we describe the molecular characterization of a pediatric HGG and the use of an integrated approach based on genomic, in vitro and in vivo testing to identify actionable targets and treatment options. Molecular analysis based on WGS performed on initial and recurrent tumor biopsies revealed mutations in TP53, TSC1 and CIC genes, focal amplification of MYCN, and copy number gains in SMO and c-MET. Transcriptomic analysis identified increased expression of MYCN, and genes involved in sonic hedgehog signaling proteins (SHH, SMO, GLI1, GLI2) and receptor tyrosine kinase pathways (PLK, AURKA, c-MET). HTS revealed no cytotoxic efficacy of SHH pathway inhibitors while sensitivity was observed to the mTOR inhibitor temsirolimus, the ALK inhibitor ceritinib, and the PLK1 inhibitor BI2536. Based on the integrated approach, temsirolimus, ceritinib, BI2536 and standard therapy temozolomide were selected for further in vivo evaluation. Using the PDX animal model (median survival 28 days) we showed significant in vivo activity for mTOR inhibition by temsirolimus and BI2536 (median survival 109 and 115.5 days respectively) while ceritinib and temozolomide had only a moderate effect (43 and 75.5 days median survival respectively). This case study demonstrates that an integrated approach based on genomic, in vitro and in vivo drug efficacy testing in a PDX model may be useful to guide the management of high risk pediatric brain tumor in a clinically meaningful timeframe.
Everolimus for Children With Recurrent or Progressive Low-Grade Glioma: Results From the Phase II PNOC001 Trial. [2023]The PNOC001 phase II single-arm trial sought to estimate progression-free survival (PFS) associated with everolimus therapy for progressive/recurrent pediatric low-grade glioma (pLGG) on the basis of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway activation as measured by phosphorylated-ribosomal protein S6 and to identify prognostic and predictive biomarkers.
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. [2023]Label="PURPOSE">Pediatric low-grade glioma (pLGG) is the most prevalent childhood brain tumor. Patients with BRAF V600 mutation-positive pLGG may benefit from treatment with dabrafenib. Part 2 of a phase I/IIa study, open-label study (NCT01677741) explores the activity and safety of dabrafenib treatment in these patients.
Development of the Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI). [2019]Measures of treatment intensity for childhood cancer are needed in research in order to control for variability in treatments. Existing measures of treatment intensity for childhood cancers do not reflect the complexities of treatment protocols for central nervous system (CNS) tumors. This paper describes the development of the Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI). PNORTI development occurred in three phases. Phase 1: five experts in pediatric neuro-oncology created a 5-point scale of treatment intensity and 42 pediatric neuro-oncology providers completed a three-part online questionnaire to evaluate the classification system and apply the rating system to 16 sample patients. Validity was determined by respondents classifying therapy modalities into intensity levels. Inter-rater reliability was calculated from ratings of the 16 sample patients. Phase 2: three experts revised the PNORTI based on survey results and 18 pediatric neuro-oncology providers evaluated the classification system. Phase 3: ten experts in pediatric neuro-oncology refined and finalized the PNORTI and rated 10 sample patients using the PNORTI. Agreement between median ratings of the survey respondents and criterion raters for chemotherapy intensity (r's = .82 and 1.0) and overall treatment intensity level (r's = .91 and .94) were high in Phases 1 and 2. Inter-rater reliability also was very high when using the PNORTI to classify the 16 sample patients in Phase 1 (median agreement of r = .93 and rICC = .99) and the 10 sample patients in Phase 3 (median agreement of r = .92 and rICC = .98). The PNORTI is a valid and reliable method for classifying the intensity of different treatment modalities used in pediatric neuro-oncology.
Phase II Weekly Vinblastine for Chemotherapy-Naïve Children With Progressive Low-Grade Glioma: A Canadian Pediatric Brain Tumor Consortium Study. [2018]Purpose Vinblastine monotherapy has shown promising activity and a low-toxicity profile in patients with pediatric low-grade glioma (PLGG) who experienced treatment failure after initial treatment with chemotherapy and/or radiation. The aim of this study was to assess the activity of vinblastine in therapy-naïve children. Patients and Methods Patients < 18 years old with unresectable and/or progressive therapy-naïve PLGG were eligible. Vinblastine was administered once per week at a dose of 6 mg/m2 intravenously over a period of 70 weeks. Vision, quality of life, neurofibromatosis type 1 (NF1) status, and BRAF mutation/fusion status were also determined and correlated with outcome. Results Fifty-four patients were enrolled onto the study, with a median age of 8 years (range, 0.7 to 17.2 years). Most patients had chiasmatic/hypothalamic tumors (55.5%), and 13 patients (24.1%) had NF1. The most common histology was pilocytic astrocytoma (46.3%). Seventeen patients were diagnosed using radiologic criteria alone. Best response to chemotherapy was centrally reviewed with a response rate (complete, partial, or minor response) of 25.9%. Disease stabilization (complete, partial, or minor response or stable disease) was achieved in 47 patients (87.0%). Visual improvement was observed in 20% of patients with optic pathway glioma. Five-year overall survival and progression-free survival (PFS) rates were 94.4% (95% CI, 88.5% to 100%) and 53.2% (95% CI, 41.3% to 68.5%), respectively, for the entire cohort. Patients with NF1 had a significantly better PFS (85.1%; 95% CI, 68.0% to 100%) when compared with patients without NF1 (42.0%; 95% CI, 29.1% to 60.7%; P = .012). Age< 3 years or > 10 years was not associated with poor outcome. Treatment was well tolerated, and quality of life was not affected during treatment. In this trial, there was no correlation between BRAF alterations and outcome. Conclusion Vinblastine administered once per week is well tolerated in children with treatment naïve PLGG. Overall survival and PFS are comparable to current therapies, with a favorable toxicity profile and a maintained quality of life.
Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors. [2021]Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPα interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Hu5F9-G4 demonstrated therapeutic efficacy in vitro and in vivo in patient-derived orthotopic xenograft models. Intraventricular administration of Hu5F9-G4 further enhanced its activity against disseminated medulloblastoma leptomeningeal disease. Notably, Hu5F9-G4 showed minimal activity against normal human neural cells in vitro and in vivo, a phenomenon reiterated in an immunocompetent allograft glioma model. Thus, Hu5F9-G4 is a potentially safe and effective therapeutic agent for managing multiple pediatric central nervous system malignancies.
Clinical experience with nimotuzumab in cuban pediatric patients with brain tumors, 2005 to 2007. [2021]Introduction Nimotuzumab, developed in Cuba, is a humanized monoclonal antibody that targets the epidermal growth factor receptor (EGFR). It has been evaluated in malignant brain tumors in adults and children, and shown to be therapeutically safe and effective in terms of increased survival and improved quality of life. Objective Describe nimotuzumab's safety profile and clinical benefits in terms of disease control and survival in pediatric patients with progressive or recurrent primary brain tumors who were included in an expanded access program. Methods An open, prospective clinical study was designed. Between December 2005 and December 2007, 22 patients were included, all of whom had an histological and/or radiological diagnosis of progressive or recurrent primary brain tumor, classified as high-grade malignant glioblastoma (n=6), diffuse brain stem glioma (n=6), ependymoblastoma (n=5), low-grade glioma (n=4), or thalamic tumor (n=1); life expectancy of at least 4 weeks; and a Karnofsky or Lansky Performance Status score of ≥50. Nimotuzumab was administered on a 100 mg weekly intravenous infusion schedule for 6 to 8 weeks, followed by a bi-weekly maintenance phase, as long as there was no deterioration in the patient's functional capacity. Therapeutic protocols were followed for administration as monotherapy or in combination with chemotherapy and/or radiotherapy. All patients received clinical and imaging follow-up. Results Nimotuzumab was well tolerated in all therapeutic modalities, even with prolonged exposure. A minority of patients reported slight or moderate adverse events, such as vomiting, mucositis and chills, as classified by the Common Terminology Criteria for Adverse Events (CTCAE). The disease was controlled in 64% (14/22) of patients; 6-month and 1-year survival rates were 82% and 64%, respectively; average survival was 20.3 months and median survival, 19 months. Recovery of neurological functions and improvement in general status were notable in patients who attained control of the disease. Conclusions As used in this study, nimotuzumab demonstrated a broad safety profile, making it acceptable for chronic use, and implied clinical benefits in terms of increased survival and improved functional status in these patients, compared to findings described in the literature. These results indicate further studies of this product are warranted.
Ushering in the next generation of precision trials for pediatric cancer. [2020]Cancer treatment decisions are increasingly based on the genomic profile of the patient's tumor, a strategy called "precision oncology." Over the past few years, a growing number of clinical trials and case reports have provided evidence that precision oncology is an effective approach for at least some children with cancer. Here, we review key factors influencing pediatric drug development in the era of precision oncology. We describe an emerging regulatory framework that is accelerating the pace of clinical trials in children as well as design challenges that are specific to trials that involve young cancer patients. Last, we discuss new drug development approaches for pediatric cancers whose growth relies on proteins that are difficult to target therapeutically, such as transcription factors.
In vivo loss of tumorigenicity in a patient-derived orthotopic xenograft mouse model of ependymoma. [2023]Label="Introduction" NlmCategory="UNASSIGNED">Ependymomas (EPN) are the third most common malignant brain cancer in children. Treatment strategies for pediatric EPN have remained unchanged over recent decades, with 10-year survival rates stagnating at just 67% for children aged 0-14 years. Moreover, a proportion of patients who survive treatment often suffer long-term neurological side effects as a result of therapy. It is evident that there is a need for safer, more effective treatments for pediatric EPN patients. There are ten distinct subgroups of EPN, each with their own molecular and prognostic features. To identify and facilitate the testing of new treatments for EPN, in vivo laboratory models representative of the diverse molecular subtypes are required. Here, we describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of posterior fossa A (PFA) EPN, derived from a metastatic cranial lesion.
A literature review of the recent radiotherapy clinical trials in pediatric brain tumors. [2019]Primary central nervous system neoplasms are the second malignancy in children following leukemia. Despite developments in neurosurgery and new drugs in chemotherapy, irradiation is an essential part of the management in most of pediatric brain tumors. A good treatment strategy should consider not only survival but also the quality of life. The new approach of radiotherapy and importance of new drugs in combined treatment are recently considered. This article summarizes the recent clinical trials conducted in pediatric brain tumors management. Results of randomized study of pre-irradiation chemotherapy versus radiotherapy alone for medulloblastoma were presented by SIOP/UKCCSG PNET-3. The French M-SFOP 98 protocol considered hyper-fractionated radiotherapy with reduced boost volume, without chemotherapy and estimated impact on early relapses and intellectual function. The influence of radiotherapy quality on survival in high-risk medulloblastoma patients was evaluated in POG Trial 9031. In the treatment of low-grade glioma in children the effectiveness of novel combination chemotherapy was considered. Role of new drugs as temozolamid, topotecan and RMP-7 was investigated in pediatric high grade glioma and brain stem tumors. Impact of combined treatment on outcome of intracranial germ-cell tumors was investigated as well.
Advances in the management of pediatric central nervous system tumors. [2008]Central nervous system tumors are the most common pediatric solid tumors and a leading cause of cancer-related mortality and morbidity in this age group. Survival rates have improved significantly over the last decades for most of the tumor types, as a consequence of improvements in neuroimaging, neurosurgery and neuroanesthesia, radiation oncology, and medical oncology. The complexity of the management of these patients requires a multidisciplinary approach and has led to the emergence of a new subspecialty of pediatric neuro-oncologists who are dedicated to the management and follow-up of this population. This review highlights the most critical advances in the diagnostic and treatment modalities of pediatric brain tumors. A specific review of the most common tumor types discusses treatment options, controversies, and ongoing developments, with an emphasis on cooperative trials.
The New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium: Organization, Objectives, and Activities. [2019]BACKGROUND: Despite advances in neuro-imaging, neurosurgery, radiation therapy, and chemotherapy, limited progress has been made in the treatment of patients with high-grade astrocytomas. The National Cancer Institute has attempted to speed advances in this field by funding CNS consortia to conduct innovative clinical trials in this patient population since 1994. METHODS: The NABTT CNS Consortium is composed of a consortium headquarters and nine member institutions with outstanding multidisciplinary expertise, clinical and laboratory research capabilities, and access to large numbers of patients with brain tumors. RESULTS: The objectives of the NABTT Consortium are to improve the therapeutic outcome for adults with primary brain tumors, to conduct basic science and clinical research, and to improve the care and quality of life of adults with primary brain tumors. NABTT's clinical studies have discovered important drug interactions between anticonvulsant and antineoplastic agents, defined the activity of paclitaxel and 9-aminocamptothecin in glioblastoma multiforme, tested a novel dose escalation strategy for brain tumor trials, and established new protocol "classes" to expedite and standardize clinical research in this field. CONCLUSIONS: Significant progress in the care of patients with primary brain tumors is likely to result from the highly focused and multidisciplinary efforts of the NIH-funded CNS consortia.