A feasibility study of the Nativis Voyager system in patients with recurrent glioblastoma multiforme (GBM): Interim results of first-in-human study.

e13506 Background: The Nativis Voyager® ulRFE™ system, a non-invasive investigational device, was studied in a first-in-human feasibility study to assess if it is a safe and feasible treatment for recurrent glioblastoma multiforme (GBM). The anti-mitotic therapy delivers ultra-low radio frequency energy ( ulRFE) profiles produced by changes in molecular electrostatic surface potential to the brain. The interim results of the first stage of a 2-stage study are presented here. Methods: In this prospective, multi-center trial, patients with GBM, following recurrence after receiving standard-of-care chemotherapy and/or radiotherapy were considered for the study. Patients were treated with Voyager alone or with Voyager plus concurrent chemotherapy or Avastin at the discretion of the investigator. Safety was assessed by incidence of any adverse events associated with the investigational therapy. Tumor progression at 8 weeks (2 cycles) was assessed by radiological response by local site. Patients were followed at least every 8 weeks during treatment and every 4 months thereafter. Results: Fourteen patients were enrolled and treated at four clinical sites across the United States. Eleven subjects were followed per protocol. Three subjects withdrew consent prior to the first radiological assessment (day 28) for reasons not associated with the study or investigational therapy, and were not included in the analysis. The local sites reported a partial response in the first 2 months of treatment in 2 of the 11 subjects. These subjects were Avastin-naïve. Two were reported to be progression free after 6 cycles (24 weeks) of treatment. No serious adverse events associated with the investigational therapy were reported. Conclusions: The Nativis Voyager appears to be feasible and safe for the treatment of recurrent GBM. Given that therapy is delivered non-invasively, and no serious adverse events attributed to the investigational therapy were reported, further prospective study in an expanded study of the investigational device is warranted. Clinical trial information: NCT02296580.

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ACTR-68. FEASIBILITY STUDY OF THE EMULATE THERAPEUTICS™ VOYAGER SYSTEM IN PATIENTS WITH RECURRENT GLIOBLASTOMA (GBM)

Neuro-Oncology ◽

10.1093/neuonc/noz175.109 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi29-vi29

Author(s):

Garni Barkhoudarian ◽

Michael Badruddoja ◽

Nicholas Blondin ◽

Ricky Chen ◽

Sajeel Chowdhary ◽

...

Keyword(s):

Overall Survival ◽

Adverse Events ◽

Skin Irritation ◽

Recurrent Glioblastoma ◽

Secondary Outcome ◽

Open Label ◽

Serious Adverse Events ◽

Radio Frequency Energy ◽

Long Term Treatment ◽

Recurrent Gbm

Abstract BACKGROUND The EMulate Therapeutics Voyager system is an investigational non-sterile, non-invasive, non-thermal, non-ionizing, portable, home-use medical device that uses a specific, localized ultra-low radio frequency energy (ulRFE®) cognate for the treatment of brain cancer. METHODS This ongoing, open-label, multi-center study (NAT-101) is being conducted in the US and Australia in patients with recurrent GBM. There are 3 treatment groups: 32 patients treated with Voyager alone, 43 patients treated with Voyager + Investigator’s choice of anti-cancer therapy, and 21 patients treated with Voyager+lomustine+/-bevacizumab. The objective of the study is to assess if the Voyager is a safe and feasible treatment for recurrent GBM. The primary outcome measure is safety, assessed by the incidence and evaluation of adverse events (AEs) associated with the Voyager. The secondary outcome measures are progression-free survival and overall survival. RESULTS Enrollment is closed, and long-term treatment and follow-up is ongoing. 96 patients were enrolled and treated. 82 patients reported at least one AE, and 18 AEs were assessed as device-related (mild-moderate; 12 headache, 2 vomiting, 1 nausea, 1 confusion, 1 insomnia, and 1 skin irritation). 31 patients reported at least one serious AE, and none were assessed as device-related. 33% of patients treated with Voyager alone and 36% of patients treated with Voyager + chemotherapy were progression-free after 6 months. 58% of patients treated with Voyager alone and 60% of patients treated with Voyager + chemotherapy remained alive after 6 months; median overall survival is 7 months (95% CI=4.4±14.3) in patients treated with Voyager alone and 10 months (95% CI=6.7±11.5) in patients treated with Voyager + chemotherapy. CONCLUSIONS The Voyager system appears to be safe and feasible for the treatment of recurrent GBM. Given that therapy is delivered non-invasively and no device-related serious adverse events were reported, further prospective study of the investigational device is planned.

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Phase II trial of Gliadel plus O6-benzylguanine (O6-BG) for patients with recurrent glioblastoma multiforme

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.1568 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 1568-1568 ◽

Cited By ~ 3

Author(s):

J. A. Quinn ◽

J. J. Vredenburgh ◽

J. N. Rich ◽

D. A. Reardon ◽

A. Desjardins ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Adverse Events ◽

Median Survival ◽

Controlled Trial ◽

Recurrent Glioblastoma ◽

Phase Iii ◽

Csf Leak ◽

Recurrent Glioblastoma Multiforme ◽

Major Mechanism ◽

Phase 2 Trial

1568 Background. The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) which removes chloroethylation or methylation damage from the O6-position of guanine. O6-BG is an AGT substrate that inhibits AGT by suicide inactivation. A previous phase III randomized, placebo-controlled trial has shown that Gliadel wafer significantly prolongs 6-month survival (55.5% for Gliadel vs. 35.6% for placebo) and median survival (28 weeks for Gliadel vs. 20 weeks for placebo) in patients with recurrent glioblastoma multiforme (GBM) (Brem et al 1995). Despite the success of Gliadel in prolonging survival we may be able to improve on this success by depleting AGT. Methods. Thus, we have designed a phase 2 trial where we define the activity and the toxicity of Gliadel in combination with a 5-day infusion of O6-BG in patients with recurrent GBM. In a prior study the O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. In order to guarantee depletion of tumor AGT activity for at least 5 days after Gliadel placement, this O6-BG bolus was repeated on days 3 and 5 while continuing the infusion. Results. To date, 24 patients have been enrolled out of a planned accrual of 50 patients. Seventeen of these patients received prior nitrosourea therapy. The 6-month survival is 68% and the median survival is 36 weeks. The adverse events include the following: 2 episodes of CSF leak (8%), 4 episodes of wound infection at craniotomy site (16%), 5 episodes of grade ≥ 3 seizures (21%) and 3 episodes of hyponatremia (12%). These adverse events were similar in frequency to those seen in patients receiving Gliadel in prior placebo-controlled Gliadel trials. Conclusions. Thus far, this data demonstrates an increase in the efficacy of Gliadel when combined with O6-BG. Twenty-six additional patients will be enrolled for a total accrual of 50 patients. [Table: see text]

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Safety and Feasibility of Convection-enhanced Delivery of Cotara for the Treatment of Malignant Glioma: Initial Experience in 51 Patients

Neurosurgery ◽

10.1227/01.neu.0000159649.71890.30 ◽

2005 ◽

Vol 56 (6) ◽

pp. 1243-1253 ◽

Cited By ~ 115

Author(s):

Sunil J. Patel ◽

William R. Shapiro ◽

Douglas W. Laske ◽

Randy L. Jensen ◽

Anthony L. Asher ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Adverse Events ◽

Malignant Glioma ◽

Tumor Volume ◽

Single Photon ◽

Photon Emission ◽

Recurrent Glioblastoma ◽

Recurrent Glioblastoma Multiforme ◽

Convection Enhanced Delivery ◽

Administered Activity

Abstract OBJECTIVE: We report the safety and feasibility of using convection-enhanced delivery to administer Cotara (Peregrine Pharmaceuticals, Inc., Tustin, CA), a novel radioimmunotherapeutic agent, to patients with malignant glioma. METHODS: Between April 1998 and November 2002, 51 patients with histologically confirmed malignant glioma received Cotara by convection-enhanced delivery. Most patients (88%) were treated with Cotara targeting tumor volume-dependent, single or multiple administrations of activity ranging from 0.5 to 3.0 mCi/cm3 of baseline clinical target volume. Two weeks after infusion, single-photon emission computed tomographic imaging determined the spatial distribution of Cotara. Patients were followed for as long as 41 months (average follow-up, 5 mo). Safety was evaluated on the basis of incidence of procedure-related, neurological, and systemic adverse events. Feasibility was evaluated in a subset of patients on the basis of the correlation between the prescribed activity and the actual activity administered to the targeted region. RESULTS: Fifty-one patients, 37 with recurrent glioblastoma multiforme, 8 with newly diagnosed glioblastoma multiforme, and 6 with recurrent anaplastic astrocytomas, were treated. Average tumor volume was 36 ± 27.6 cm3 (range, 5–168 cm3). Of the 67 infusions, 13 (19%), 52 (78%), and 2 (3%) delivered less than 90%, 100 ± 10%, and more than 110%, respectively, of the prescribed administered activity to the targeted region. Treatment-emergent, drug-related central nervous system adverse events included brain edema (16%), hemiparesis (14%), and headache (14%). Systemic adverse events were mild. Several patients had objective responses to Cotara. CONCLUSION: The majority of Cotara infusions delivered between 90 and 110% of the prescribed administered activity to the targeted region. This method of administration has an acceptable safety profile compared with literature reports of other therapeutics delivered by convection-enhanced delivery.

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