Dataset Information

ACTR-54. OPEN-LABEL PHASE 1 CLINICAL TRIAL TESTING PERSONALIZED AND TARGETED INTERVENTION WITH SKULL REMODELLING SURGERY TO MAXIMIZE LEVELS OF TTFIELDS INTENSITY FOR HIGHER TREATMENT BENEFIT - THE OPTIMAL TTF STUDY

ABSTRACT: Abstract We present an ongoing open label phase 1 investigator-sponsored trial (NCT02893137) testing safety/efficacy of a novel therapeutic concept for recurrent glioblastoma (GBM). The intervention combines best choice chemotherapy with tumor treating fields (TTFields) and personalized targeted skull remodeling surgery. The objective of skull remodeling surgery is to create paths, which facilitate electric current flow through into the region of pathology. This may involve formation of strategically placed minor craniectomies or burr holes and thinning of the skull. Finite element (FE) calculations indicate that skull remodeling surgery provides a marked and focal enhancement (~100%) of TTFields intensity without significantly compromising patient safety. Patient accrual began Dec 2016. As of June 2017 seven patients have been screened and six out of fifteen patients enrolled. Major eligibility criteria include age > 18 years, first recurrence supratentorial GBM, Karnofsky performance score (KPS) > 60, focal tumor < 2 cm to cortical surface, lack of uncontrollable epilepsy, and lack of significant co-morbidity. Upon inclusion, personalized FE-calculations are performed to validate TTFields enhancement > 25% due by skull remodeling surgery. The primary endpoint is toxicity assessed by CTCAEv4.0. Secondary endpoints include overall survival, progression free survival (PFS), PFS at six months (PFS6), objective response rate (RANO), quality of life (EORTC QLQ-C30 and BN20), KPS, and steroid dose. Follow-up is 18 months and includes regular toxicity assessment (6 week intervals) as well as quality of life and response assessments (3 month intervals). Patients are censored at the end of scheduled follow-up, occurrence of serious or unacceptable adverse events, withdrawal of consent, or loss to follow-up. Interim analysis will be performed upon censoring of the first five patients. The tested concept holds promising potential for improving TTFields outcome by enhancing field intensity in the tumor. The trial will hopefully lay the foundation for future efficacy investigation.

SUBMITTER: Korshoej A

PROVIDER: S-EPMC5692142 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Abstract Background We present a pre-specified interim analysis of an ongoing open-label, investigator-sponsored phase 1 trial (NCT02893137) testing safety/efficacy of a new rGBM treatment. The intervention combines personalized skull-remodeling (SR) surgery with TTFields and best-choice chemotherapy. SR-surgery involves minor craniectomy, burr-holes, and/or skull thinning personalized to enhance TTFields intensity focally in the tumor. Material and Methods Accrual began Dec 2016 (planned total 15 patients). Eligibility: Age > 18 years, first recurrence focal supratentorial GBM (RANO), and KPS ? 70. Personalized electric field calculations were conducted to validate TTFields enhancement > 25% by SR-surgery. Patients were right-censored for OS and PFS at the time of analysis and excluded upon progression, death, SUSARs, or unacceptable AEs. Primary endpoints: Toxicity (CTCAEv4.0). Secondary endpoints: OS, PFS, PFS6, objective response rate (iRANO), quality of life, KPS, and steroid dose. Results The interim analysis was based on data prior to April 1, 2018. Safety data were analyzed for all enrolled patients and efficacy for all patients treated with TTFields. 16 patients were screened, 1 declined, and 2 had KPS < 70. Of the 13 enrolled patients, 3 were excluded prior to TTFields treatment (1 female due to radionecrosis/non-recurrence, 1 male due to post-op infection, and 1 female due to neurodeficit). All included patients (9 male and 1 female) had GBM IDH-wt tumors (4 MGMT-methylated). Median KPS was 90 (range 70–100) and median age 55 years (range 49 to 67). All patients received maximum safe resection at recurrence (4 had no residual tumor (RANO), 4 had non-measurable disease, and 2 had measurable disease). 8 patients received adjuvant bevacizumab monotherapy (10 mg/kg every 2 weeks, median number of cycles 9.5, range 4 to 23) and 2 received temozolomide rechallenge (200 mg/m2 every 4 weeks, 3 and 4 cycles, respectively). The mean skull-defect area was 10.5 cm2 (range 7 to 24 cm2), the median field enhancement 37 % (range 25 to 61%), and the median TTFields compliance 91% (range 61 to 95%). Within the observation period 5 patients had progression, 3 died, 5 were censored for PFS, and 7 for OS. We observed no SUSARs or grade 4/5 SAEs, but 5 grade 3 SAEs (2 generalized seizures in patients with known epilepsy, 1 post-op infection, 1 diarrhea, and 1 DVT). 2 patients had grade 1–2 skin rash, and 1 had grade 1–2 headaches. Median OS was 15.5 months, 95%-CI: 5.9-NA, median PFS 9.5 months, 95%-CI: 3.7-NA, and PFS6 58%, 95%-CI: 0.27–0.90. 1 patient had complete response during TTFields treatment. Conclusion SR-surgery including craniectomy is not associated with additional toxicity in combination with TTFields and holds promising potential for improving TTFields outcome by focally enhancing the field intensity in the tumor. A future phase 2/3 trial is being planned for efficacy assessment.

Project description:BackgroundTumour-treating fields therapy is a locoregional, anti-cancer treatment. Efficacy and safety of tumour-treating fields therapy in adults with newly diagnosed glioblastoma were demonstrated in the pivotal phase 3 EF-14 study (NCT00916409). Here, we report post-approval data of tumour-treating fields therapy in Japanese patients with newly diagnosed glioblastoma.MethodsUnsolicited post-marketing surveillance data from Japanese patients with newly diagnosed glioblastoma treated with tumour-treating fields therapy (December 2016-June 2020) were retrospectively analysed. The primary endpoints were skin, neurological and psychiatric adverse events. The secondary endpoints were 1- and 2-year overall survival rates, and the 6-month progression-free survival. adverse events were analysed using MedDRA v24.0. The overall survival and progression-free survival were assessed using the Kaplan-Meier survival analysis (log-rank testing). The Cox proportional hazard regression analyses were also performed.ResultsForty patients with newly diagnosed glioblastoma were enrolled (62.5% male; median age 59 years; median baseline Karnofsky Performance Scale score 90). The most common tumour-treating-fields-therapy-related adverse event was beneath-array local skin reaction (60% of patients). The adverse events were mostly mild to moderate in severity. Neurological disorders were observed in 2.5% patients (one patient reported dysesthesia). No psychiatric disorders were reported. The 1- and 2-year overall survival rates were 77.9% (95% CI 60.6-88.3) and 53.6% (35.5-68.7%), respectively. The 6-month progression-free survival was 77.5% (61.2-87.6%). These survival rates compare favourably with those in the EF-14 trial (1- and 2-year overall survival rates: 73% [69-77%] and 43% [39-48%], respectively; 6-month progression-free survival rate: 56% (51-61%).ConclusionThis post-approval, real-world evidence study revealed no new safety signals and suggests the safety and efficacy of tumour-treating fields therapy in Japanese patients with newly diagnosed glioblastoma.

Dataset Information

ACTR-54. OPEN-LABEL PHASE 1 CLINICAL TRIAL TESTING PERSONALIZED AND TARGETED INTERVENTION WITH SKULL REMODELLING SURGERY TO MAXIMIZE LEVELS OF TTFIELDS INTENSITY FOR HIGHER TREATMENT BENEFIT - THE OPTIMAL TTF STUDY

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets