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

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1568-1568 ◽  
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]

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

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2036-2036 ◽  
Author(s):  
J. A. Quinn ◽  
J. J. Vredenburgh ◽  
J. N. Rich ◽  
D. A. Reardon ◽  
A. Desjardins ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Controlled Trial ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Csf Leak ◽  
Recurrent Glioblastoma Multiforme ◽  
Major Mechanism ◽  
Phase 2 Trial ◽  
Grade 3

2036 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 (G) significantly prolongs 6-month survival (55.5% for G vs. 35.6% for placebo) and median survival (28 weeks for G vs. 20 weeks for placebo) in patients with recurrent glioblastoma multiforme (GBM) (Brem et al 1995). Despite the success of G 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 G 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 G placement, this O6-BG bolus was repeated on days 3 and 5 while continuing the infusion. Results: To date, 47 patients have been enrolled out of a planned accrual of 50 patients. The 6-month survival is 80% and the median survival is 47 weeks. The adverse events include the following: 3 episodes of grade 3 CSF leak (6%), 7 episodes of grade 3 wound infection at craniotomy site (15%), 6 episodes of hyponatremia (13%), 3 episodes of hydrocephalus (6%), 1 episode of hygroma (2%), 1 episode of infectious meningitis (2%), 1 episode of arachnoiditis (2%), 1 episode of grade 3 fever (2%). Conclusions: Thus far, this data demonstrates an increase in the efficacy of G when combined with O6-BG. Three additional patients will be enrolled for a total accrual of 50 patients. [Table: see text]

Bevacizumab Plus Irinotecan in Recurrent Glioblastoma Multiforme

2007 ◽  
Vol 25 (30) ◽  
pp. 4722-4729 ◽  
Author(s):  
James J. Vredenburgh ◽  
Annick Desjardins ◽  
James E. Herndon ◽  
Jennifer Marcello ◽  
David A. Reardon ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Recurrent Glioblastoma Multiforme ◽  
Initial Cohort ◽  
Endothelial Growth Factor

Purpose The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. We performed a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan. Patients and Methods This phase II trial included two cohorts of patients. The initial cohort, comprising 23 patients, received bevacizumab at 10 mg/kg plus irinotecan every 2 weeks. The dose of irinotecan was based on the patient's anticonvulsant: Patients taking enzyme-inducing antiepileptic drugs (EIAEDs) received 340 mg/m2, and patients not taking EIAEDs received 125 mg/m2. After this regimen was deemed safe and effective, the irinotecan schedule was changed to an accepted brain tumor regimen of four doses in 6 weeks, in anticipation of a phase III randomized trial of irinotecan versus irinotecan and bevacizumab. The second cohort, comprising 12 patients, received bevacizumab 15 mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. Each cycle was 6 weeks long and concluded with patient evaluations, including magnetic resonance imaging. Results The 6-month progression-free survival among all 35 patients was 46% (95% CI, 32% to 66%). The 6-month overall survival was 77% (95% CI, 64% to 92%). Twenty of the 35 patients (57%; 95% CI, 39% to 74%) had at least a partial response. One patient developed a CNS hemorrhage, which occurred in his 10th cycle. Four patients developed thromboembolic complications (deep venous thrombosis and/or pulmonary emboli). Conclusion Bevacizumab and irinotecan is an effective treatment for recurrent glioblastoma multiforme and has moderate toxicity.

Health-Related Quality of Life in Patients Treated With Temozolomide Versus Procarbazine for Recurrent Glioblastoma Multiforme

2000 ◽  
Vol 18 (7) ◽  
pp. 1481-1491 ◽  
Author(s):  
D. Osoba ◽  
M. Brada ◽  
W.K. A. Yung ◽  
M. Prados
Keyword(s):  
Quality Of Life ◽  
Glioblastoma Multiforme ◽  
Disease Progression ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Health Related Quality ◽  
Recurrent Glioblastoma Multiforme ◽  
Related Quality ◽  
Health Related

PURPOSE: To determine whether chemotherapy with temozolomide (TMZ) versus procarbazine (PCB) for recurrent glioblastoma multiforme (GBM) was associated with improvement in health-related quality of life (HRQOL). PATIENTS AND METHODS: HRQOL was assessed at baseline and during treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and a Brain Cancer Module (BCM20) in two clinical trials that enrolled a total of 366 patients. Two hundred eighty-eight patients provided HRQOL data that could be used for analysis; 109 patients received TMZ in a phase II study, whereas 89 patients received TMZ and 90 received PCB in a randomized phase III study. Changes from baseline in the scores of seven preselected HRQOL domains (role and social functioning, global quality of life [QOL], visual disorders, motor dysfunction, communication deficit, and drowsiness) were calculated for all groups. Statistical significance, effect sizes, and proportions of patients with improved HRQOL scores (changes of ≥ 10 points) were calculated. RESULTS: Before disease progression, patients treated with TMZ were found to have an improvement in most of the preselected HRQOL domain scores compared with their baseline (pretreatment) scores. Those who were progression-free on TMZ at 6 months had improvement in all the preselected HRQOL domains. Conversely, patients treated with PCB reported deterioration in HRQOL that was independent of whether or not the disease had progressed by 6 months. Patients with disease progression, regardless of treatment, experienced a sharp decline in all domains at the time of progression. CONCLUSION: Treatment with TMZ was associated with improvement in HRQOL scores compared with treatment with PCB. The deterioration reported by PCB-treated patients was likely because of toxicity. Delaying disease progression by treatment with TMZ is beneficial to the HRQOL status of patients with recurrent GBM.

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

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13506-e13506
Author(s):  
Garni Barkhoudarian
Keyword(s):  
Glioblastoma Multiforme ◽  
Adverse Events ◽  
Feasibility Study ◽  
Human Study ◽  
The United States ◽  
Concurrent Chemotherapy ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Serious Adverse Events ◽  
Radio Frequency Energy

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.

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

Neurosurgery ◽  
2005 ◽  
Vol 56 (6) ◽  
pp. 1243-1253 ◽  
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.

scholarly journals Rekurrens glioblastomában szenvedő betegek kezelése bevacizumab-monoterápiával

2016 ◽  
Vol 157 (13) ◽  
pp. 500-503 ◽  
Author(s):  
Dániel Sinkó ◽  
Csaba Nemeskéri
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Free Survival

Introduction: The prognosis of patients with recurrent glioblastoma is poor, as the median survival does not exceed 6 months. Aim: The aim of this study was to evaluate the efficacy of bevacizumab monotherapy in patients with recurrent glioblastoma multiforme. Method: From April, 2012 to June, 2015, 40 patients with recurrent glioblastoma multiforme were treated with bevacizumab in a dose of 10 mg/kg every 2 weeks. Results: The average progression-free survival was 6.4 months (2–22 months), and the 6-month progression-free survival was 42.5%. The six-month overall survival was 82.5%, which corresponds to those published in the literature. Conclusions: Bevacizumab monotherapy improves progression-free survival in patients with recurrent glioblastoma multiforme. Orv. Hetil., 2016, 157(13), 500–503.

scholarly journals Scale to Predict Survival After Surgery for Recurrent Glioblastoma Multiforme

2010 ◽  
Vol 28 (24) ◽  
pp. 3838-3843 ◽  
Author(s):  
John K. Park ◽  
Tiffany Hodges ◽  
Leopold Arko ◽  
Michael Shen ◽  
Donna Dello Iacono ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Surgical Resection ◽  
Median Survival ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
Postoperative Survival ◽  
Recurrent Glioblastoma Multiforme ◽  
Factors Associated ◽  
Recurrent Gbm

Purpose Despite initial treatment with surgical resection, radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) virtually always recurs. Surgery is sometimes recommended to treat recurrence. In this study, we sought to devise a preoperative scale that predicts survival after surgery for recurrent glioblastoma multiforme. Patients and Methods The preoperative clinical and radiographic data of 34 patients who underwent re-operation of recurrent GBM tumors were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards regression modeling. The factors associated with decreased postoperative survival (P < .05) were used to devise a prognostic scale which was validated with a separate cohort of 109 patients. Results The factors associated with poor postoperative survival were: tumor involvement of prespecified eloquent/critical brain regions (P = .021), Karnofsky performance status (KPS) ≤ 80 (P = .030), and tumor volume ≥ 50 cm3 (P = .048). An additive scale (range, 0 to 3 points) comprised of these three variables distinguishes patients with good (0 points), intermediate (1 to 2 points), and poor (3 points) postoperative survival (median survival, 10.8, 4.5, and 1.0 months, respectively; P < .001). The scale identified three statistically distinct groups within the validation cohort as well (median survival, 9.2, 6.3, and 1.9 months, respectively; P < .001). Conclusion We devised and validated a preoperative scale that identifies patients likely to have poor, intermediate, and good relative outcomes after surgical resection of a recurrent GBM tumor. Application of this simple scale may be useful in counseling patients regarding their treatment options and in designing clinical trials.

scholarly journals Phase II study of XR5000 (DACA) administered as a 120-h infusion in patients with recurrent glioblastoma multiforme

2002 ◽  
Vol 13 (5) ◽  
pp. 777-780 ◽  
Author(s):  
C. Twelves ◽  
M. Campone ◽  
B. Coudert ◽  
M. Van den Bent ◽  
M. de Jonge ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme
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