Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioma

Diffuse Intrinsic Pontine Glioma

Ependymoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Brain Stem Neoplasms

Infratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

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).

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.

The Optune, a.k.a. Tumor Treating Fields (TTFields), will be worn for a minimum of 18 hours a day, with a recommendation of 22 hours/day for at least 23 days in a 28-day cycle. Cycle 1 includes 7 days training period, followed by 28 days treatment (total 35 days). The patients will receive multiple 28-day cycles of continuous Optune treatment. In the absence of treatment related serious adverse events or disease progression, Optune will continue up to 26 cycles.

Optune System (NovoTTF-200A System, Tumor Treating Fields, TTFields)

In Stratum II patients will be treated with standard of care focal RT concurrently with Optune followed by Optune treatment. This study specifies a 1 cm clinical target volume margin.The duration of the first cycle of therapy will be from Day 1 of RT to 14 days after completion of RT (approximately 8 weeks total). Subsequent cycles of therapy will be 28 days in duration. The Optune device will be worn for a minimum of 18 hours/day, with a recommendation of 22 hours/day. For the phase I part, the initial treatment will involve RT delivery with Optune arrays remaining in place but turned off. If this is not tolerated, two treatment de-escalation levels are planned, Specifically, Level -1: remove the Optune arrays during RT delivery and reapply daily after RT; Level -2: initiate Optune therapy after completion of RT. The established safe treatment approach from phase I will be investigated for feasibility and efficacy in phase II. Treatment with Optune may continue for up to 5 years.

Concurrent Optune and RT followed by Optune System alone

Emily Atwood

Anna Rosdil, MSN

Stewart Goldman, MD

Nathan Robison, MD

Sonia Partap, MD, MS

Kathleen Dorris, MD

Jason Fangusaro, MD

Tobey MacDonald, MD

Ira Dunkel, MD

Natasha Pillay Smiley, DO

CCHMC Cancer Line

James Felker, MD

Giles Robinson, MD

Melissa Johnson

Anna Vinitsky, MD

Patricia Baxter, MD

Susan Burlingame, CCRP

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).

The primary objectives of Stratum 1 are: 1) to evaluate the feasibility of treatment with Optune in pediatric patients with recurrent/refractory/progressive supratentorial malignant glioma or ependymoma, and 2) to describe the Optune device treatment-related toxicities in children with recurrent/refractory/progressive supratentorial malignant glioma or ependymoma.

The primary objectives of Stratum 2 are: 1) to describe the safety and tolerability of concurrent Optune therapy and RT (Phase I component), 2) to evaluate the feasibility of treatment with concurrent Optune and RT (Phase II component), and 3) to estimate the overall survival (Phase II component) in children and adolescents with newly diagnosed DIPG treated with concurrent Optune therapy and standard RT.

The Optune System produces alternating electrical fields, called tumor treatment fields (TTFields) by means of 4 transducer arrays placed on the shaved scalp. The very low intensity, intermediate frequency electric fields impair the growth of tumor cells through the arrest of cell division and inducing apoptosis. Preclinical studies have demonstrated TTFields synergistically enhance the efficacy of irradiation in glioma cell lines.

Optune will be worn for a minimum of 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 Optune treatment may continue for up to 5 years in Stratum 2 if the participant is deriving benefit and in the absence of significant treatment-related toxicity. Patients will be followed for 2 years from the cessation of protocol treatment in Stratum 1, and for 3 years from the cessation of Optune device treatment in Stratum 2 for the monitoring of unexpected later developing toxicities and to document disease progression, event-free and overall survival.

For patients in Stratum 1, the therapy will be deemed feasible for patients who are able to use the device for ≥ 18 hours/day for at least 23 days out of 28 days of cycle one (feasibility assessment period). A total of 20 patients need to be assessed with an interim analysis to be conducted after the first 11 patients. Kaplan-Meier estimates of EFS for all eligible patients who use the device for at least 1 day will be provided separately for the two histology-based cohorts i.e. HGG and Ependymoma.

For patients in Stratum 2, the study will consist of two parts: a phase I portion to evaluate the safety and tolerability of concurrent Optune and RT; and a phase II portion to evaluate the feasibility and efficacy of concurrent Optune and standard RT. The therapy will be deemed feasible for patients who are able to use the device for ≥ 18 hours/day for at least 40 of the 49 days of the feasibility assessment period of cycle one, which consists of concurrent Optune and RT. Up to 18 evaluable patients may need to be assessed for the phase I component. A total of 30 patients need to be assessed for the phase II component (6 of whom will be counted from the phase I component). The design also incorporates 2 interim analyses for futility assessed when 9 and 14 events are observed.

The study includes two independent strata. Stratum 1 is a single-arm safety and feasibility study. While stratum 2 is a phase I/II study which consists 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.

Open-label single-arm study within each stratum

Optune for Children With High-Grade Glioma or Ependymoma, and Optune With Radiation Therapy for Children With DIPG

Feasibility Trial of Optune for Children With Recurrent or Progressive Supratentorial High-Grade Glioma or Ependymoma, and Feasibility and Efficacy Trial of Optune in Conjunction With Radiation Therapy for Children With Newly Diagnosed DIPG

The Pediatric Brain Tumor Consortium (PBTC) ensures that high dimensional molecular data generated from PBTC samples will be submitted to the NIH Database of Genotypes and Phenotypes (dbGaP) or other NIH-designated data repository. PBTC is required to make data available to other investigators for use in research projects. An investigator requesting data from published PBTC studies will submit a proposal describing the studies from which data are requested, the requested data, and a list of investigators in the project and their affiliated institutions, along with the investigator's CV to the PBTC Steering Committee for review. Once approved, the requesting investigator will be asked to complete a Data Transfer Agreement before the release of deidentified data. Requests for data are typically only considered once the primary study manuscript has been published though exceptions may be made in the event of long delays in the primary study data publication.

Stratum 1: Device Usage Compliance will be reported to assess the feasibility of the device treatment.

Stratum 1: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0.

Stratum 2:The number of participants with DLTs per protocol Section 5.4.

Stratum 2: Device Usage Compliance will be reported to assess the feasibility of the device treatment when administered concurrent with RT. The device treatment will be considered feasible for a patient who use the device for ≥18 hours/day for at least 40 of 49 days (23 of 28 days if the second dose de-escalation is utilized for phase II) of the feasibility period of Cycle 1.

Stratum 2: OS is defined as time from enrollment to death due to any cause.

Stratum 1: The response rate is calculated according to the bi-dimensional tumor measurement at the end of treatment compared with the baseline measurements.

Stratum 1: The event-free survival is the interval of time between date of initiation of protocol treatment and minimum date of documentation of progressive disease, second malignancy, death due to any cause, or date of last follow-up.

Stratum 1:The anti-tumor activity will be classified as complete response, partial response, stable disease, and progressive disease per protocol specified criteria. The compliance in Optune device use will be calculated as the actual hours of Optune device usage per day.

Stratum 1:The Quality of Life Scores will be reported at baseline, and with each cycle using PROMIS and Neuro-QoL Stigma, in which the mean score of the general population is 50 and standard deviation is 10.

Stratum 1: We will summarize the tumor-type specific ADC value at baseline and at various times on treatment as well as within-patient changes over time. The ADC value of responders will be compared to the ADC value of those with progressive diseases at baseline and over time.

Stratum 2: The response rate is calculated according to the bi-dimensional tumor measurement at the end of treatment compared with the baseline measurements.

Stratum 2: The event-free survival will be measured from the date of initial treatment to the earliest date of disease progression, second malignancy or death for any reason for patients who fail; and to the date of last contact for patients who remain at risk for failure.

Stratum 2: A patient will be considered compliant if he/she uses the device for ≥18 hours/day for at least 23 days in a 28-day cycle.

The Quality of Life (QoL) Scores will be reported at baseline, and with each cycle using Patient Reported Outcomes Measurement Information System (PROMIS) and Quality of Life in Neurological Disorders (Neuro-QoL) Stigma Scale, in which the mean score of the general population is 50 and standard deviation is 10.

The PROMIS is rated 0-4 with 0 being "never" (better outcome) and 4 being "almost always," (worse outcome).

Neuro-QOL Scale is rated 1-5 with 1 being "never" (better outcome) and 5 being "always," (worse outcome).

We will summarize the tumor-type specific ADC value at baseline and at various times on treatment as well as within-patient changes over time. The ADC value of responders will be compared to the ADC value of those with progressive diseases at baseline and over time.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Optune for Children With High-Grade Glioma or Ependymoma, and Optune With Radiation Therapy for Children With DIPG	NCT03033992	Malignant Gliom... Ependymoma Diffuse Intrins...	Optune System (... Concurrent Optu...	3 Years - 21 Years	Pediatric Brain Tumor Consortium
Optune for Children With High-Grade Glioma or Ependymoma, and Optune With Radiation Therapy for Children With DIPG	NCT03033992	Malignant Gliom... Ependymoma Diffuse Intrins...	Optune System (... Concurrent Optu...	3 Years - 21 Years	Pediatric Brain Tumor Consortium

Spots Global Cancer Trial Database for concurrent optune and rt followed by optune system alone