Current and future directions for Phase II trials in high-grade glioma

2013 ◽  
Vol 13 (4) ◽  
pp. 369-387 ◽  
Author(s):  
Brian M Alexander ◽  
Eudocia Q Lee ◽  
David A Reardon ◽  
Patrick Y Wen
Keyword(s):  
Phase Ii ◽  
High Grade Glioma ◽  
High Grade ◽  
Phase Ii Trials ◽  
Future Directions

scholarly journals An Observational Study of the First Experience with Bevacizumab for the Treatment of Patients with Recurrent High-Grade Glioma in Two Belgian University Hospitals

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
M. Huylebrouck ◽  
S. Lv ◽  
J. Duerinck ◽  
A. Van Binst ◽  
I. Salmon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Response ◽  
Metabolic Response ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
High Grade ◽  
University Hospitals ◽  
Phase Ii Trials ◽  
Antiangiogenic Effect

Background. Bevacizumab (BEV), a humanized immunoglobulin G1 monoclonal antibody that inhibits VEGF has demonstrated activity against recurrent high-grade gliomas (HGG) in phase II clinical trials.Patients and Methods. Data were collected from patients with recurrent HGG who initiated treatment with BEV outside a clinical trial protocol at two Belgian university hospitals.Results. 19 patients (11 M/8 F) were administered a total of 138 cycles of BEV (median 4, range 1–31). Tumor response assessment by MRI was available for 15 patients; 2 complete responses and 3 partial responses for an objective response rate of 26% for the intent to treat population were observed on gadolinium-enhanced T1-weighted images; significant regressions on T2/FLAIR were documented in 10 out of 15 patients (67%). A reduced uptake on PET was documented in 3 out of 4 evaluable patients. The six-month progression-free survival was 21% (95% CI 2.7–39.5). Two patients had an ongoing tumor response and remained free from progression after 12 months of BEV treatment.Conclusions. The activity and tolerability of BEV were comparable to results from previous prospective phase II trials. Reduced uptake on PET suggests a metabolic response in addition to an antiangiogenic effect in some cases with favorable clinical outcome.

scholarly journals Phase II evaluation of sunitinib in the treatment of recurrent or refractory high‐grade glioma or ependymoma in children: a children's Oncology Group Study ACNS1021

2016 ◽  
Vol 5 (7) ◽  
pp. 1416-1424 ◽  
Author(s):  
Cynthia Wetmore ◽  
Vinay M. Daryani ◽  
Catherine A. Billups ◽  
James M. Boyett ◽  
Sarah Leary ◽  
...  
Keyword(s):  
Phase Ii ◽  
High Grade Glioma ◽  
High Grade ◽  
Oncology Group ◽  
Oncology Group Study

scholarly journals AT-46 * VORINOSTAT AND BEVACIZUMAB FOR RECURRENT HIGH-GRADE GLIOMA: INTERIM ANALYSIS OF A PHASE II CLINICAL TRIAL

2014 ◽  
Vol 16 (suppl 5) ◽  
pp. v18-v18
Author(s):  
K. Peters ◽  
D. Reardon ◽  
D. Randazzo ◽  
S. Dutton ◽  
A. Edwards ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Interim Analysis ◽  
High Grade Glioma ◽  
Phase Ii Clinical Trial ◽  
High Grade

Phase II trial of sunitinib malate in patients with temozolomide refractory recurrent high-grade glioma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2038-2038 ◽  
Author(s):  
B. Neyns ◽  
C. Chaskis ◽  
M. Dujardin ◽  
H. Everaert ◽  
J. Sadones ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cerebral Blood Volume ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
High Grade Glioma ◽  
Gene Copy ◽  
Dynamic Susceptibility ◽  
High Grade ◽  
Antiangiogenic Effect ◽  
Daily Dose

2038 Background: High-grade gliomas (HGG) are characterized by neo-angiogenesis. Sunitinib is a small molecule tyrosine kinase inhibitor that inhibits multiple receptors (including VEGFR, PDGFR, and c-Kit). We investigated sunitinib for the treatment of patients (pts) with temozolomide (TMZ) refractory recurrent HGG. Methods: Pts were recruited according to a 2-stage phase II design and received a daily dose of 37.5 mg sunitinib. T1 ± Gd and T2 weighted MRI images were obtained after 4 and 8 weeks of sunitinib and q8 weeks thereafter. We assessed the antiangiogenic effect by calculating the cerebral blood volume (CBV) and cerebral blood flow (CBF) from dynamic susceptibility (DSC) based perfusion MRI and determined the lesion-to-normal-white matter CBV (CBVLTN) and CBF (CBFLTN) ratios. Uptake of fluorinated fenyl-methyl-alanine within the CNS was assessed by PET at baseline and reassessed in responding pts. Results: 21 pts were enrolled (median age 43 [range 34–71]; M/F 15/6; KPS 90–80: 11 pts, KPS 70–60: 10 pts). All pts had PD following surgery, RT and TMZ. A total of 142 treatment weeks (range 2–84) were evaluated; 81% of the administrations were at the 37,5 mg-, 19% at the 25 mg dose level. Most frequent AEs were: skin toxicity (gr2, n = 1; gr 3, n = 1), fatigue (gr 2, n = 4), hypertension (gr 2, n = 3), diarrhea (gr 2, n = 2), mucositis (gr 3; n = 1), afebrile- (gr 2, n = 3) and febrile neutropenia (gr 3, n = 1; gr 4, n = 1), thrombocytopenia (gr 2, n = 4; gr 3, n = 1; gr 4, n = 1), and lymphocytopenia (gr 2, n = 2; gr 3, n = 4). Decrease in CBVLTN and CBFLTN was observed in 6/14 evaluable pts after 4 weeks of sunitinib, 5/19 evaluable pts had SD on T1±Gd after 8 weeks; one pt experienced a marked clinical improvement with a reduction in the tumor metabolism on PET. After a median follow-up of 11 months, median TTP and -OS are1,6 and 3,8 months respectively. Three pts with a secondary glioblastoma (age <40 year) had an objective PR when administered CCNU at PD under sunitinib (with a TTP of 2, 8 and +9 mths respectively). Characterization of the VEGFR, PDGFR, and Kit gene copy numbers and protein expression in the tumors is ongoing. Conclusions: Sunitinib at a continuous daily dose of 37.5 mg has a transient antiangiogenic effect in pts with recurrent HGG but is of insufficient clinical benefit to warrant further investigation as a single agent. [Table: see text]

Phase II study of sunitinib and irinotecan in patients with recurrent high-grade glioma (HGG).

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e12537-e12537 ◽  
Author(s):  
S. Grisanti ◽  
R. Pedersini ◽  
V. D. Ferrari ◽  
R. Liserre ◽  
F. Consoli ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
High Grade Glioma ◽  
High Grade

Phase II study of temsirolimus in children with high-grade glioma, neuroblastoma, and rhabdomyosarcoma.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 9541-9541 ◽  
Author(s):  
B. Geoerger ◽  
M. W. Kieran ◽  
S. Grupp ◽  
S. Blaney ◽  
D. Perek ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
High Grade Glioma ◽  
High Grade

BMX-HGG: Phase II trial of newly diagnosed high-grade glioma treated with concurrent radiation therapy, temozolomide, and BMX-001.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS2577-TPS2577
Author(s):  
Katherine B. Peters ◽  
Adam Louis Cohen ◽  
Nicholas A. Butowski ◽  
John L. Villano ◽  
Pierre Giglio ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
White Matter ◽  
Cancer Therapy ◽  
Phase Ii ◽  
Functional Assessment ◽  
Phase Ii Study ◽  
High Grade Glioma ◽  
High Grade ◽  
Newly Diagnosed ◽  
Who Grade

TPS2577 Background: Patients diagnosed with malignant high-grade gliomas (WHO grade III-IV) experience significant morbidity and mortality associated with these cancers. While the mainstay of therapy for patients with newly diagnosed high-grade glioma is surgery followed by concurrent chemotherapy and radiation therapy (RT), the outcomes remain very poor. BMX-001 (MnTnBuOE-2-PyP5+) is a metalloporphyrin with differential action in response to radiation therapy and chemotherapy-induced oxidative stress. Early preclinical studies demonstrated BMX-001’s ability to act as a radioprotectant to healthy tissue such as a central nervous white matter and as a radiosensitizer to cancer cells, in particular, human glioblastoma xenografts. We evaluated the safety of BMX-001 in combination with concurrent RT and temozolomide (TMZ) in a phase I study of newly diagnosed high-grade glioma patients, and we found that BMX-001 is safe and well-tolerated in this population. The maximum tolerated dose of BMX-001 during concurrent RT and TMZ was determined to be 28 mg delivered subcutaneously (SC) followed by 16 biweekly SC doses at 14 mg (Peters et al., Neuro-Oncology 2018). Methods: For this multi-site, open-label, phase II study (NCT02655601), we will randomize approximately 160 patients 1:1 to concurrent RT and TMZ with BMX-001 versus concurrent RT and TMZ alone. Key eligibility criteria include newly diagnosed histologically confirmed high-grade glioma (WHO III-IV), 18 ≥ years, and Karnofsky performance status ≥ 70%. The primary endpoint is overall survival. Secondary endpoints include cognitive performance as assessed by standardized cognitive testing, bone marrow protection, safety and tolerability, progression-free survival, overall tumor response rate, and plasma pharmacokinetics. Exploratory endpoints are health-related quality of life (as assessed by Functional Assessment of Cancer Therapy–Brain, Functional Assessment of Cancer Therapy-Cognition, and Functional Assessment of Chronic Illness Therapy-Fatigue), qualitative hair loss, and white matter integrity (as measured by MRI diffusion tensor/susceptibility imaging). Since November 2018, this phase II study has enrolled 64 of 160 high-grade glioma patients at six sites with future sites planned to be implemented. Clinical trial information: NCT02655601 .

scholarly journals Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma

2012 ◽  
Vol 48 (2) ◽  
pp. 253-262 ◽  
Author(s):  
Birgit Geoerger ◽  
Mark W. Kieran ◽  
Stephan Grupp ◽  
Danuta Perek ◽  
Jill Clancy ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
High Grade Glioma ◽  
High Grade
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