NCT03033992

Brief Summary

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).

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
80

participants targeted

Target at P50-P75 for not_applicable

Timeline
63mo left

Started Apr 2017

Longer than P75 for not_applicable

Geographic Reach
1 country

11 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress64%
Apr 2017Jul 2031

First Submitted

Initial submission to the registry

January 17, 2017

Completed
10 days until next milestone

First Posted

Study publicly available on registry

January 27, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

April 4, 2017

Completed
14.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 22, 2031

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 21, 2031

Last Updated

March 5, 2026

Status Verified

August 1, 2025

Enrollment Period

14.1 years

First QC Date

January 17, 2017

Last Update Submit

March 3, 2026

Conditions

Outcome Measures

Primary Outcomes (5)

  • The feasibility of treatment with the Optune device in pediatric patients with recurrent/refractory/progressive supratentorial malignant glioma and ependymoma.

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

    days 8 through 35 of cycle 1

  • The Optune device treatment-related toxicities in children with recurrent/refractory/progressive supratentorial malignant glioma and ependymoma.

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

    2 years

  • The type and frequency of Device Limiting Toxicities (DLTs) associated with the Optune treatment given concurrently with RT in children and adolescents with newly diagnosed DIPG.

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

    5 years

  • The feasibility of concurrent Optune therapy and RT in children and adolescents with newly diagnosed DIPG.

    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.

    days 8 through 56 of cycle 1 (days 8 through 35 of cycle 1 if the second dose de-escalation is utilized for phase II)

  • The overall survival

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

    3 years

Secondary Outcomes (10)

  • The Response Rate

    2 years

  • The Event-Free Survival

    2 years

  • The association of anti-tumor activity with compliance in Optune device use within the context of a small feasibility study.

    2 years

  • The association between the Optune device usage and the health-related quality of life of children and families undergoing this therapy.

    2 years

  • The association of apparent diffusion coefficient (ADC) values within the tumor and correlate with response to Optune treatment and EFS.

    2 years

  • +5 more secondary outcomes

Study Arms (2)

Treatment (Optune System)

EXPERIMENTAL

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).

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

Treatment (Concurrent Optune/focal radiation therapy followed by Optune-only therapy)

EXPERIMENTAL

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.

Combination Product: Concurrent Optune and RT followed by Optune System alone

Interventions

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.

Also known as: Optune System (NovoTTF-200A System)
Treatment (Optune System)

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.

Treatment (Concurrent Optune/focal radiation therapy followed by Optune-only therapy)

Eligibility Criteria

Age3 Years - 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Age: at the time of enrollment Stratum 1: ≥ 5 years but ≤ 21 Stratum 2: ≥ 3 years but ≤ 21
  • Diagnosis:
  • Stratum 1: Patients must have a histologically confirmed diagnosis of supratentorial high-grade glioma or supratentorial ependymoma that is recurrent, progressive or refractory.
  • Stratum 2: Patients with newly diagnosed DIPG
  • Patients with 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, are eligible without histologic confirmation.
  • Note: Patients with typical DIPG who undergo a biopsy are eligible provided the tumor is a diffuse glioma WHO Grade II-IV with OR without H3 K27M mutation.
  • Patients with pontine lesions that do not meet these MR imaging criteria will be eligible if there is histologic confirmation diffuse glioma WHO Grade II-IV with H3 K27M-mutation.
  • 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:
  • This 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:
  • This disease must be located primarily in the pons
  • Prior Therapy:
  • Stratum 1: Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
  • +35 more criteria

You may not qualify if:

  • Systemic Illness: Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), 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.
  • Other Malignancy: Patients with a history of any other malignancy.
  • Concurrent Therapy: Patients who are receiving any other anticancer or investigational drug therapy are not eligible.
  • Inability to Participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to device usage plan, other study procedures, and study restrictions.
  • Stratum 1 Tumor Location: Patients with primarily infra-tentorial or spinal cord tumor are not eligible.
  • Tumor Dissemination: Patients for who clinical suspicion is present of metastatic disease in the CSF or Spine must have MRI of Spine and CSF obtained (Lumbar puncture or through ommaya, EVD or Shunt) with negative cytology. Patients with CSF that is positive for tumor cells or metastatic disease found on MRI are ineligible.
  • Skull Defects: Patients with major skull defects (such as missing bone without replacement) are not eligible.
  • Neurological Disorder: Patients with active implanted electronic devices in the brain or spinal cord such as programmable VP shunts, deep brain stimulators, vagus nerve stimulators, are not eligible.
  • Cardiac Disorder: Patients with pacemaker, defibrillator, or documented significant arrhythmia, are not allowed.
  • Intracranial Objects: Patients with foreign body intracranially, such as bullet fragments, are not allowed, with the exception of VP-shunts (non-programmable) and Ommaya catheters.
  • Allergy: Patients with history of hypersensitivity to conductive hydrogel are not eligible.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90026, United States

Location

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

GliomaEpendymomaDiffuse Intrinsic Pontine Glioma

Condition Hierarchy (Ancestors)

Neoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueBrain Stem NeoplasmsInfratentorial NeoplasmsBrain NeoplasmsCentral Nervous System NeoplasmsNervous System NeoplasmsNeoplasms by SiteBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Study Officials

  • Stewart Goldman, MD

    Phoenix Children's Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Masking Details
Open-label single-arm study within each stratum
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 17, 2017

First Posted

January 27, 2017

Study Start

April 4, 2017

Primary Completion (Estimated)

May 22, 2031

Study Completion (Estimated)

July 21, 2031

Last Updated

March 5, 2026

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, ICF, CSR

Locations