Dataset Information

PDCT-07. FEASIBILITY TRIAL OF TTFIELDS (TUMOR TREATING FIELDS) FOR CHILDREN WITH RECURRENT OR PROGRESSIVE SUPRATENTORIAL HIGH-GRADE GLIOMA (HGG) AND EPENDYMOMA: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY: PBTC-048

ABSTRACT: Abstract BACKGROUND Children with recurrent or progressive pediatric CNS tumors have poor prognoses. Optune delivers TTFields, an anti-mitotic FDA-approved cancer therapy, for adult patients with newly diagnosed and recurrent supratentorial GBM. Methods This multicenter trial [NCT03033992] examines the feasibility and device-related toxicity of TTFields in 20 children aged 5–21 years with recurrent supratentorial HGG and ependymoma. Secondary objectives include: response rate, event-free survival, compliance and QoL. Feasibility in this trial is defined as the ability of pediatric subjects to wear Optune ?18 hours/day for at least 23/28 days of cycle one following a 7-day learning period. Treatment may continue up to 26 cycles based on observed benefit and safety. QOL instruments include PROMIS and Neuro-QOL. Following enrollment of the 11th evaluable subject, the study will be temporarily suspended to share interim feasibility and safety data with the FDA. RESULTS This planned interim analysis included 11 patients (7 males/4 females) with supratentorial tumors: ten HGG and one ependymoma. Median age was 14.2 (6.4–21.3) years. Ten patients were evaluable (1 Progressive Disease) during the feasibility period) and 4 remained on study through 4 cycles and one patient is currently on Cycle 14. One grade 5 intracranial hemorrhage not associated with the device and no grade IV toxicities occurred, 3 patients had seizures (grade 1–3), fatigue, scalp pain, localized rash, and headache (none greater than grade 3). Of the 10 evaluable patients, 7 satisfied the feasibility criteria for the Optune therapy, which is above the prespecified threshold of at least 6/11. CONCLUSION This is the first prospective safety and feasibility trial for Optune in children with recurrent supratentorial HGG and ependymoma. Preliminary results indicate feasibility with minimal toxicity. Accrual to the study is ongoing. An amendment is in progress adding a stratum for newly diagnosed diffuse intrinsic pontine glioma (DIPG) patients.

SUBMITTER: Goldman S

PROVIDER: S-EPMC6217083 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Project description:BackgroundTumor Treating Fields (TTFields) are an anti-neoplastic treatment modality delivered via application of alternating electric fields using insulated transducer arrays placed directly on the skin in the region surrounding the tumor. A Phase 3 clinical trial has demonstrated the effectiveness of continuous TTFields application in patients with glioblastoma during maintenance treatment with Temozolomide. The goal of this study was to evaluate the efficacy of combining TTFields with radiation treatment (RT) in glioma cells. We also examined the effect of TTFields transducer arrays on RT distribution in a phantom model and the impact on rat skin toxicity.MethodsThe efficacy of TTFields application after induction of DNA damage by RT or bleomycin was tested in U-118 MG and LN-18 glioma cells. The alkaline comet assay was used to measure repair of DNA lesions. Repair of DNA double strand breaks (DSBs) were assessed by analyzing ?H2AX or Rad51 foci. DNA damage and repair signaled by the activation pattern of phospho-ATM (pS1981) and phospho-DNA-PKcs (pS2056) was evaluated by immunoblotting. The absorption of the RT energy by transducer arrays was measured by applying RT through arrays placed on a solid-state phantom. Skin toxicities were tested in rats irradiated daily through the arrays with 2Gy (total dose of 20Gy).ResultsTTFields synergistically enhanced the efficacy of RT in glioma cells. Application of TTFields to irradiated cells impaired repair of irradiation- or chemically-induced DNA damage, possibly by blocking homologous recombination repair. Transducer arrays presence caused a minor reduction in RT intensity at 20 mm and 60 mm below the arrays, but led to a significant increase in RT dosage at the phantom surface jeopardizing the "skin sparing effect". Nevertheless, transducer arrays placed on the rat skin during RT did not lead to additional skin reactions.ConclusionsAdministration of TTFields after RT increases glioma cells treatment efficacy possibly by inhibition of DNA damage repair. These preclinical results support the application of TTFields therapy immediately after RT as a viable regimen to enhance RT outcome. Phantom measurements and animal models imply that it may be possible to leave the transducer arrays in place during RT without increasing skin toxicities.

Project description:Abstract BACKGROUND Optune-delivered TTFields is a promising anti-mitotic FDA-approved cancer therapy in adult patients with high-grade gliomas (HGG), although effectiveness is not yet proven in pediatric patients. A multicenter trial [NCT03033992] evaluating the feasibility and device-related toxicity for children with recurrent or progressive supratentorial high-grade glioma (HGG) and ependymoma is being conducted. This presentation reports the interim health-related quality of life (HRQOL) and device-use experiences reported by patients and parents. METHODS Participating patients (aged 5–21 years) and one of their parents completed the following measures at baseline and prior to each intervention cycle: PROMIS Fatigue, Anger, Anxiety, Depressive Symptoms, Mobility, Upper Extremity Function, and Peer Relationships and Neuro-QOL Stigma. Participants completed an exit survey when they were off the study regarding their experiences wearing the device. RESULTS This planned interim analysis included 11 patients (7 males/4 females) with supratentorial tumors: ten HGG and one ependymoma. Median age was 14.2 (6.4–21.3) years. Patients reported worse HRQOL than the norms on all domains. Of these 11 patients, 6 completed the exit survey. No significant changes (p< 0.05) between the baseline and the final assessment were found except for Stigma. Patients perceived less stigma at baseline than at the final assessment (t=2.82, p=0.0370). Of these 6 parents who completed the Exit Survey: most considered wearing the device to be easy (n=5).Patient reminders were unnecessary (n=5), patients rarely/didn’t complain (n=4) or refuse (n=5) to wear the device, there was rare/no (n=4) difficulty with daily activities because of the device, and patients were not (n=4) or sometimes (n=2) embarrassed to wear the device. CONCLUSION Preliminary results indicate Optune-delivered TTFields therapy is feasible and accepted by children and parent with no evidence of negatively impacting patients’ QOL. Accrual has been expanded beyond the interim analysis.

Dataset Information

PDCT-07. FEASIBILITY TRIAL OF TTFIELDS (TUMOR TREATING FIELDS) FOR CHILDREN WITH RECURRENT OR PROGRESSIVE SUPRATENTORIAL HIGH-GRADE GLIOMA (HGG) AND EPENDYMOMA: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY: PBTC-048

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