EORTC 1709/CCTG CE.8: A phase III trial of marizomib in combination with standard temozolomide-based radiochemotherapy versus standard temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2072-TPS2072 ◽  
Author(s):  
Patrick Roth ◽  
Jaap C. Reijneveld ◽  
Thierry Gorlia ◽  
Frederic Dhermain ◽  
Filip Yves Francine Leon De Vos ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Primary Objective ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Open Label ◽  
Phase Iii Trial ◽  
Newly Diagnosed Glioblastoma

TPS2072 Background: The standard treatment for patients with newly diagnosed glioblastoma comprises maximum safe surgery, radiotherapy (RT), and concomitant and up to six cycles of maintenance temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). Despite this intense therapy, the prognosis remains poor and there is an urgent need to develop new therapeutic options. Marizomib is a novel, irreversible and brain-penetrant pan-proteasome inhibitor. Following its successful assessment in phase I trials in patients with newly diagnosed as well as recurrent glioblastoma, marizomib is now being investigated in a phase III trial. Methods: EORTC 1709/CCTG CE.8 is a multicenter, randomized, controlled, open label phase III superiority trial. Eligibility criteria include histologically confirmed newly diagnosed glioblastoma and a performance status ≥70. Approximately a total of 750 patients will be enrolled and randomized 1:1. Stratification factors include institution, age, Karnofsky performance status and extent of surgery. The primary objective of this study is to compare overall survival in patients receiving marizomib in addition to standard of care (TMZ/RT→TMZ) with patients receiving standard treatment only. The testing strategy specifies the determination of this objective in both the intent-to-treat population and the subgroup of patients with tumors harboring an unmethylated MGMT promoter. Secondary endpoints include progression-free survival, safety, neurocognitive function and quality of life. The study is accompanied by a translational research program. The study will be opened at 50 EORTC sites in Europe and done as an intergroup collaboration with the Canadian Cancer Trials Group (CCTG) with 25 sites in Canada and additional sites in the US. Patient enrolment started in June 2018 and as of January 29, 2019, a total of 85 patients have been randomized. An update on the enrolment status will be provided at the ASCO conference. Clinical trial information: NCT03345095.

scholarly journals P14.124 EORTC 1709/CCTG CE.8: A phase III trial of marizomib in combination with standard temozolomide-based radiochemotherapy versus standard temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii98-iii98 ◽  
Author(s):  
P Roth ◽  
J Reijneveld ◽  
T Gorlia ◽  
F Dhermain ◽  
F De Vos ◽  
...  
Keyword(s):  
Performance Status ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Open Label ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND The standard of care for patients with newly diagnosed glioblastoma includes maximal debulking surgery followed by radiotherapy (RT), and concomitant as well as maintenance therapy with the alkylating agent, temozolomide (TMZ). However, the prognosis remains poor and novel treatment strategies are urgently needed. Targeting the proteasome has been considered a promising anti-cancer approach for several years. Marizomib is a novel, irreversible and pan-proteasome inhibitor, which crosses the blood-brain barrier and has been assessed in phase I trials in patients with newly diagnosed or recurrent glioblastoma. MATERIAL AND METHODS EORTC 1709/CCTG CE.8 is a randomized, controlled, open label phase III superiority trial. Patients with histologically confirmed newly diagnosed glioblastoma and a performance status >70 are eligible. Patients are randomized in a 1:1 ratio to receive standard of care (TMZ/RT→TMZ) alone or TMZ/RT→TMZ plus marizomib. The study aims at enrolling 750 patients. Stratification factors include study site, age, performance status and extent of resection. The primary objective of this trial is to compare overall survival in patients receiving marizomib in addition to standard of care with those receiving standard treatment only. The testing strategy specifies the determination of this objective in the intent-to-treat population as well as the subgroup of patients with MGMT-unmethylated tumors. Secondary endpoints include progression-free survival, safety, neurocognitive function and quality of life. A translational research program has been set up. The study will be activated at approximately 50 EORTC sites across Europe, 25 sites in Canada and additional sites in the US. Patient recruitment started in June 2018 and as of April 29, 2019, a total of 164 patients have been randomized. An update on the enrolment status will be provided at the EANO meeting. ClinicalTrials.gov Identifier: NCT03345095

EORTC 1709/CCTG CE.8: A phase III trial of marizomib in combination with temozolomide-based radiochemotherapy versus temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2004-2004
Author(s):  
Patrick Roth ◽  
Thierry Gorlia ◽  
Jaap C. Reijneveld ◽  
Filip Yves Francine Leon De Vos ◽  
Ahmed Idbaih ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Standard Treatment ◽  
Early Stage ◽  
Karnofsky Performance Status ◽  
Methylation Status ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Newly Diagnosed Glioblastoma ◽  
Secondary Endpoints

2004 Background: Patients with newly diagnosed glioblastoma receive postoperative standard therapy with radiotherapy (RT), and concomitant and up to six cycles of maintenance temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). Marizomib is a novel, irreversible and brain-penetrant pan-proteasome inhibitor with encouraging findings in preclinical models and early-stage clinical trials for patients with newly diagnosed and recurrent glioblastoma. Therefore, a phase 3 trial was designed to explore the activity of marizomib in addition to TMZ/RT→TMZ. ClinicalTrials.gov Identifier: NCT03345095 Methods: EORTC 1709/CCTG CE.8 is a multicenter, randomized, controlled, open label phase 3 superiority trial. Eligibility criteria included histologically confirmed newly diagnosed glioblastoma and a Karnofsky performance status (KPS) > 70. Eligible patients were stratified for institution, age, KPS as well as extent of surgery, and centrally randomized in a 1:1 ratio. The primary objective of this study is to compare overall survival (OS) in patients receiving marizomib in addition to standard treatment with patients receiving standard treatment only. Secondary endpoints include progression-free survival (PFS), safety, neurocognitive function, and quality of life. Results: The study was opened at 49 EORTC sites in Europe, 23 CCTG sites in Canada, and 8 sites in the US. Patient enrolment started in June 2018 and was close to completion at the time of a planned interim analysis in September 2020. A total of 749 patients (of the planned 750) were randomized when the IDMC recommended to discontinue enrollment. Age, KPS and extent of resection were well balanced between the 2 study arms. No difference in median OS was observed between the standard arm (15.9 months) and the marizomib arm (15.7 months; HR = 0.99). Median PFS was 6.1 vs. 6.2 months (HR = 1.02). Patients in the marizomib group had more often grade 3/4 treatment-emergent adverse events (TEAE) compared to the standard therapy group (42.6% vs. 20.5%), including ataxia, hallucinations and headache. Conclusions: The addition of marizomib to standard radiochemotherapy did not improve OS or PFS in patients with newly diagnosed glioblastoma. Final survival analyses including determination of MGMT promoter methylation status and analyses of other secondary endpoints are ongoing. Clinical trial information: NCT03345095.

Final results of a randomized phase III trial of nimotuzumab for the treatment of newly diagnosed glioblastoma in addition to standard radiation and chemotherapy with temozolomide versus standard radiation and temoziolamide.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2033-2033 ◽  
Author(s):  
Manfred Westphal ◽  
Ferdinand Bach
Keyword(s):  
Tumor Hypoxia ◽  
Residual Tumor ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Open Label ◽  
Clear Trend ◽  
Significant Treatment ◽  
Phase Iii Trial ◽  
Newly Diagnosed Glioblastoma

2033 Background: The receptor for epidermal growth factor (EGF-R) has consistently been found expressed or overexpressed in human malignant glioma disease. Therapeutic targeting of the EGF-R has shown mixed responses which appear to be restricted by specific features of the tumor cells.Nimotuzumab binds preferentially to highly over expressing cells, a phase III trial was initiated to test efficacy in glioma. Methods: Nimotuzumab was tested in an open label, randomized, multicenter Phase III trial in patients with histologically confirmed, newly diagnosed glioblastoma. 12 consecutive weekly infusions of 400mg during standard radiotherapy with Temozolomide followed by biweekly infusions of 400mg arm A was randomized against standard radio chemotherapy alone arm B. Primary endpoint was PFS as determined by centralized neuro-imaging review. OS as secondary endpoint with quality of life, safety as additional parameters.MGMT and EGF-R were assessed where sufficient materials could be retrieved as well as tumor hypoxia. Results: Between 2007 and 2010, 149 patients were randomized and 142 were available for analysis. Stratification according to resection status resulted in 40 pts in the treatment arm and 41 in the control arm with residual tumor and 31 vs 30 pts without residual tumor. PFS: 12 month was 25.5% arm A vs 20.3% in arm B (p = 0.78) and OS: 679 days vs 596 days. For non - methylated MGMT the difference was most notable: OS arm A 28 pats: 19.6 months vs arm B 28 pats 15.0 months EGF-R amplification, gave no clear signal, neither was there a statistically significant treatment effect between with or without residual tumor. Tumor hypoxia does not appear to have predictive value in the overall group but possibly in subgroups.AEs and SAEs did not reveal a new specific toxicity profile beyond the known side effects from glioma treatment with current standard. Conclusions: Nimotuzumab shows a clear trend towards efficacy in MGMT non-methylated glioblastoma patients. Safety profile and indications for subgroup efficacy potentially justify focused evaluation of antibody therapy against glioblastoma.

Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation: Final results of the multicenter, randomized, open-label, controlled, phase III CENTRIC study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. LBA2009-LBA2009
Author(s):  
Roger Stupp ◽  
Monika E. Hegi ◽  
Thierry Gorlia ◽  
Sara Erridge ◽  
Danica Grujicic ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Standard Treatment ◽  
Mgmt Promoter Methylation ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Open Label ◽  
Daily News ◽  
Methylguanine Dna Methyltransferase ◽  
Newly Diagnosed Glioblastoma ◽  
Final Text

LBA2009 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Sunday, June, 2, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.

OC-0333 Dose-painting multicenter phase III trial in newly diagnosed glioblastoma: the SPECTRO-GLIO trial

2021 ◽  
Vol 161 ◽  
pp. S246-S247
Author(s):  
A. Laprie ◽  
G. Noel ◽  
L. Chaltiel ◽  
G. Truc ◽  
M. Sunyach ◽  
...  
Keyword(s):  
Phase Iii ◽  
Newly Diagnosed ◽  
Dose Painting ◽  
Phase Iii Trial ◽  
Multicenter Phase ◽  
Newly Diagnosed Glioblastoma

VELCADE/Dexamethasone (Vel/Dex) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantation (ASCT) in Newly Diagnosed Multiple Myeloma (MM): An Interim Analysis of the IFM 2005-01 Randomized Multicenter Phase III Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 56-56 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Gerald Marit ◽  
Denis Caillot ◽  
Philippe Casassus ◽  
Thierry Facon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Interim Analysis ◽  
Primary Objective ◽  
Phase Iii ◽  
Induction Treatment ◽  
Newly Diagnosed ◽  
Serious Adverse Events ◽  
Phase Iii Trial ◽  
Significance Level ◽  
Β2 Microglobulin

Abstract ASCT is considered the standard of care for patients up to 65 years of age with MM. The optimal induction treatment prior to ASCT is still unknown. VAD is a commonly used regimen but is associated with a number of toxicities, administrative inconvenience, and a complete remission (CR) rate of typically less than 10%. Recently the combination thalidomide/Dex was reported to induce a higher overall response rate than Dex alone in newly diagnosed patients, but with significantly more toxicities, especially deep vein thrombosis, and a 4% CR rate (Rajkumar et al, J Clin Oncol 2006;24:431–6). In a phase II trial we have evaluated the combination of Vel 1.3mg/m2 D1, 4, 8, 11 with Dex 40mg/D D1-4, D9-12, for 4 consecutive 21-D cycles (Dex only on D1-4 during cycles 3–4). This combination was well tolerated and yielded a 21% CR/nCR rate with successful stem cell harvest and engraftment (Harousseau et al, Haematologica 2006). In 2005, the IFM initiated a multicenter randomized phase III trial comparing Vel/Dex with VAD as induction treatment of patients with newly diagnosed MM up to the age of 65. The primary objective of the study is the CR (negative immunofixation) plus nCR (CR but positive immunofixation) rate after 4 cycles. A secondary objective is to evaluate the role of consolidation with 2 courses of DCEP (Dex, cyclophosphamide, etoposide, cisplatin). Patients were randomized at diagnosis among 4 arms (A1: 4 cycles of VAD; A2: 4 cycles of VAD + 2 cycles of DCEP; B1: 4 cycles of Vel/Dex; B2: 4 cycles of Vel/Dex + 2 cycles of DCEP); stratification was by cytogenetics and β2 microglobulin. Stem cell collection was performed between cycle 3 and cycle 4 after priming with G-CSF (10μg/kg/D × 6 D). At the end of induction (± DCEP consolidation) treatment, patients received melphalan 200mg/m2 plus ASCT. Enrollment of 480 patients is planned, to detect a 10% higher CR/nCR rate with Vel/Dex (20% vs 10%) with 80% power (two-sided test, significance level 0.05). An interim analysis is planned when 222 patients have been evaluated for response at the end of induction. As of July 2006, 304 patients have been enrolled. Randomization of the 222 patients to be considered for interim analysis was completed on May 19th. Baseline characteristics include: median age 55y; 140M, 82F; β2 microglobulin >3mg/L in 54%; del13 by FISH in 45%. The occurrence of serious adverse events (SAEs) was similar between the VAD and Vel/Dex arms (31% with VAD, 33% with Vel/Dex). The most frequent SAEs were pneumopathy (5.3% VAD, 4.0% Vel/Dex), thrombosis (2.7% VAD, 3.3% Vel/Dex), and peripheral neuropathy (1.3% VAD, 3.3% Vel/Dex). We intend to present results from the interim analysis.

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