Phase II Study of Imatinib Mesylate Plus Hydroxyurea in Adults With Recurrent Glioblastoma Multiforme

2005 ◽  
Vol 23 (36) ◽  
pp. 9359-9368 ◽  
Author(s):  
David A. Reardon ◽  
Merrill J. Egorin ◽  
Jennifer A. Quinn ◽  
Jeremy N. Rich ◽  
Idharan Gururangan ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Imatinib Mesylate ◽  
Phase Ii ◽  
Cox Regression ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Cox Regression Analysis

Purpose We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Patients and Methods Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). Results Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. Conclusion Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

Randomized Phase II Study of Cilengitide, an Integrin-Targeting Arginine-Glycine-Aspartic Acid Peptide, in Recurrent Glioblastoma Multiforme

2008 ◽  
Vol 26 (34) ◽  
pp. 5610-5617 ◽  
Author(s):  
David A. Reardon ◽  
Karen L. Fink ◽  
Tom Mikkelsen ◽  
Timothy F. Cloughesy ◽  
Alison O'Neill ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Antitumor Activity ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Wide Range ◽  
First Recurrence ◽  
Arginine Glycine Aspartic Acid

PurposeCilengitide, an inhibitor of αvβ3 and αvβ5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. The current multicenter phase II study was conducted to evaluate the activity and safety of cilengitide in GBM patients at first recurrence.Patients and MethodsEligible patients were randomly assigned to receive either 500 or 2,000 mg of cilengitide twice weekly on a continuous basis. Patients were assessed every 4 weeks. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included PFS, overall survival (OS), and radiographic response, as well as quality-of-life and pharmacokinetic assessments.ResultsEighty-one patients were enrolled, including 41 on the 500-mg arm and 40 on the 2,000-mg arm. The safety profile of cilengitide was excellent, with no significant reproducible toxicities observed on either arm. Antitumor activity was observed in both treatment cohorts but trended more favorably among patients treated with 2,000 mg, including a 6-month PFS of 15% and a median OS of 9.9 months.ConclusionCilengitide monotherapy is well tolerated and exhibits modest antitumor activity among recurrent GBM patients. Additional studies integrating cilengitide into combinatorial regimens for GBM are warranted.

First-Line Chemotherapy With Cisplatin Plus Fractionated Temozolomide in Recurrent Glioblastoma Multiforme: A Phase II Study of the Gruppo Italiano Cooperativo di Neuro-Oncologia

2004 ◽  
Vol 22 (9) ◽  
pp. 1598-1604 ◽  
Author(s):  
Alba A. Brandes ◽  
Umberto Basso ◽  
Michele Reni ◽  
Francesca Vastola ◽  
Alicia Tosoni ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Hematologic Toxicity ◽  
Recurrent Glioblastoma Multiforme

Purpose Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). Conclusion The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.

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

A stratified phase II study of cetuximab for the treatment of recurrent glioblastoma multiforme: Preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1558-1558 ◽  
Author(s):  
J. Sadones ◽  
C. Chaskis ◽  
E. J. Joosens ◽  
L. A. Dhondt ◽  
J. Baurain ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Recurrent Glioblastoma ◽  
Gene Copy ◽  
Recurrent Glioblastoma Multiforme ◽  
Egfr Gene ◽  
Recurrent Gbm

1558 Background: The Epidermal Growth Factor Receptor (EGFR) gene is frequently amplified and mutated in high-grade gliomas. We are investigating the activity of the EGFR-targeted monoclonal antibody cetuximab for the treatment of patients (pts) with recurrent glioblastoma multiforme (GBM) following surgery, radiotherapy and chemotherapy. Methods: Adult pts with recurrent GBM are allocated to two parallel treatment strata according to the amplification status of the EGFR gene (determined by FISH). According to a Simon two-stage phase II study design 1 response in 13 pts/stratum is required to continue recruitment and complete the second stage of pt recruitment. Cetuximab is administered at 400 mg/m2 (2 hour infusion) day 1 and 250 mg/m2 day 8 and for all subsequent weekly doses (1 hour infusion). Results: Between May and December 2005, 17 pts were recruited (10 without EGFR-ampl, 4 with EGFR-ampl and 3 under investigation); 4F/13M; median age 51 years, range 32–67). Recruitment is ongoing. Sixteen pts initiated study treatment; 1 pt withdrew consent before the initiation of therapy. Treatment related toxicity in the first 94 treatment cycles consisted of grade 1/2 folliculitis/dermitis in all treated pts. Grade 3 adverse events consisted of thrombocytopenia (n=1 pt), diminished consciousness (n=1 pt), dizziness/confusion (n=1 pt), infectious bronchopneumonia (n=1 pt), and infectious cellulitis (n=1 pt). Thirteen pts have been evaluated for response ≤ week 8 of study treatment. Eleven pts had progression of disease. Two patients had SD at 8 weeks (follow-up is ongoing). Conclusions: These preliminary data suggest that cetuximab can be safely administered to pretreated patients with recurrent GBM. Updated results regarding safety and activity as well as a correlative study of EGFR and PTEN expression and gene copy number of the GBM and response to cetuximab will be presented at the meeting. No significant financial relationships to disclose.

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.

Abstract 3701: Phase II study of BIBF1120 in recurrent glioblastoma multiforme

2012 ◽  
Author(s):  
Ulrik Lassen ◽  
Morten Mau-Soerensen ◽  
Aida Muhic ◽  
Eva Ehrnrooth ◽  
Hans S. Poulsen
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme
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