A phase III trial of marizomib in combination with temozolomide-based radiochemotherapy versus temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma. Started summer 2018. 749 patients randomized in a 1:1 ratio. No difference in median OS was observed between the standard arm (15.9 months) and the marizomib arm (15.7 months; HR = 0.99).
Dr Patrick Roth speaks to ecancer in an online interview for ASCO 2021 about a phase III trial of marizomib in combination with temozolomide-based radiochemotherapy versus temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma. He explains that glioblastoma still has a very poor prognosis despite intense research efforts and comprehensive standard treatment. Dr Roth reports that the data obtained from the interim analysis shows no survival benefit from the addition of marizomib and an increase in adverse events, leading to enrollment for the trial ending. He discusses analysis that is still ongoing.
2021 ASCO Annual Meeting
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.
Authors: Patrick Roth, Thierry Gorlia, Jaap C. Reijneveld, Filip Y. De Vos, Ahmed Idbaih, Jean-Sebastien Frenel, Emilie Le Rhun, José M. Sepulveda Sánchez, James R. Perry, Laura Masucci, Pierre Freres, Hal W. Hirte, Clemens Seidel, Anna Maria E. Walenkamp, Frederic Dhermain, Martin J. Van Den Bent, Christopher J. O'Callaghan, Maureen Vanlancker, Warren P. Mason, Michael Weller
Abstract Disclosures Research Funding: Celgene / BMS
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 https://meetinglibrary.asco.org/record/195893/abstract
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