NCT03033992

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

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 3 Years – 21 Years
• Healthy volunteers: Not accepted

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).

Detailed description

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.

Conditions

• Malignant Glioma
• Ependymoma
• Diffuse Intrinsic Pontine Glioma

Interventions

Type	Name	Description
DEVICE	Optune System (NovoTTF-200A System, Tumor Treating Fields, TTFields)	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.
COMBINATION_PRODUCT	Concurrent Optune and RT followed by Optune System alone	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.

Timeline

• Start date: 2017-04-04
• Primary completion: 2031-05-22
• Completion: 2031-07-21
• First posted: 2017-01-27
• Last updated: 2026-04-06

Locations

11 sites across 1 country: United States

Regulatory

• FDA-regulated device study