RTOG 0525: A randomized phase III trial comparing standard adjuvant temozolomide (TMZ) with a dose-dense (dd) schedule in newly diagnosed glioblastoma (GBM).

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.

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Evaluation of pseudoprogression rates and tumor progression patterns in a phase III trial of bevacizumab plus radiotherapy/temozolomide for newly diagnosed glioblastoma

Neuro-Oncology ◽

10.1093/neuonc/now091 ◽

2016 ◽

Vol 18 (10) ◽

pp. 1434-1441 ◽

Cited By ~ 46

Author(s):

Wolfgang Wick ◽

Olivier L. Chinot ◽

Martin Bendszus ◽

Warren Mason ◽

Roger Henriksson ◽

...

Keyword(s):

Tumor Progression ◽

Phase Iii ◽

Newly Diagnosed ◽

Phase Iii Trial ◽

Newly Diagnosed Glioblastoma ◽

Progression Patterns

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Radiotherapy (RT) and concomitant and adjuvant temozolomide (TMZ) versus radiotherapy alone for newly diagnosed glioblastoma (GBM): Overall results and recursive partitioning analysis (RPA) of a phase III randomized trial of the EORTC brain tumor and radiotherapy groups and the NCIC clinical trial group

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2004.06.081 ◽

2004 ◽

Vol 60 (1) ◽

pp. S162 ◽

Cited By ~ 3

Author(s):

R. Mirimanoff ◽

W. Mason ◽

R. Kortmann ◽

M. Van den Bent ◽

B. Fisher ◽

...

Keyword(s):

Clinical Trial ◽

Brain Tumor ◽

Randomized Trial ◽

Recursive Partitioning ◽

Phase Iii ◽

Trial Group ◽

Newly Diagnosed ◽

Adjuvant Temozolomide ◽

Newly Diagnosed Glioblastoma ◽

Radiotherapy Alone

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RTOG 0525: Molecular correlates from randomized phase III trial of newly diagnosed glioblastoma (GBM).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.lba2000 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. LBA2000-LBA2000 ◽

Cited By ~ 1

Author(s):

K. D. Aldape ◽

M. Wang ◽

E. P. Sulman ◽

D. P. Cahill ◽

M. Hegi ◽

...

Keyword(s):

Phase Iii ◽

Newly Diagnosed ◽

Phase Iii Trial ◽

Newly Diagnosed Glioblastoma

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A phase III randomized controlled trial of short-course radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with glioblastoma (CCTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.18_suppl.lba2 ◽

2016 ◽

Vol 34 (18_suppl) ◽

pp. LBA2-LBA2 ◽

Cited By ~ 21

Author(s):

James R. Perry ◽

Normand Laperriere ◽

Christopher J. O'Callaghan ◽

Alba Ariela Brandes ◽

Johan Menten ◽

...

Keyword(s):

Clinical Trial ◽

Controlled Trial ◽

Phase Iii ◽

Newly Diagnosed ◽

Adjuvant Temozolomide ◽

Short Course ◽

Newly Diagnosed Glioblastoma ◽

To Receive ◽

Short Course Radiotherapy ◽

Clinical Trial Information

LBA2 Background: The EORTC (26981-22981)/NCIC CTG (CE.3) RCT in newly diagnosed glioblastoma (GB) showed increased overall survival (OS) with concomitant and adjuvant temozolomide (TMZ) added to radiotherapy (RT). Pts were 18-71 (median 56) years; however, a trend of decreasing benefit from the addition of TMZ with increasing age was noted. Recent RCTs in elderly GB detected non-inferiority of 40 Gy/15 v 60 Gy/30 RT and superior survival was noted for MGMT-methylated pts treated with TMZ alone. However, whether the addition of TMZ to RT improves survival in elderly pts remained unanswered. Methods: We conducted a global randomized phase III clinical trial for patients ≥ 65 yrs with histologically confirmed newly diagnosed GB, ECOG 0-2, randomized 1:1 to receive 40Gy/15 RT v 40Gy/15 RT with 3 weeks of concomitant TMZ plus monthly adjuvant TMZ until progression or 12 cycles. Stratification was by centre, age (65-70, 71-75, or 76+), ECOG 0,1 vs 2, and biopsy vs resection. Results: 562 pts were randomized, 281 on each arm; median age 73 yrs (range 65-90), male 61%, PS 0/1 77%, resection 68%. RT+TMZ significantly improved OS over RT alone (median 9.3m v 7.6m, HR 0.67, 95%CI 0.56-0.80, p < 0.0001) and significantly improved PFS (median 5.3m v 3.9m, HR 0.50, 95%CI 0.41 – 0.60, p < 0.0001). Tissue from 462 pts was provided and adequate for MGMT analysis in 354 to date. In MGMT methylated patients (n = 165) OS for RT+TMZ v RT was 13.5 m and 7.7m respectively (HR: 0.53 (95% C.I. 0.38, 0.73, p = 0.0001). In MGMT unmethylated patients (n = 189) OS for RT + TMZ v RT was 10.0m vs 7.9m respectively (HR 0.75 (95% C.I. 0.56 – 1.01, p = 0.055). QoL analyses showed no differences in functional domains of QLQC30 and BN20 but were worse in the RT/TMZ arm for nausea, vomiting, and constipation. Systemic therapy after PD was reported in 39% on RT+TMZ v 41% on RT. Conclusions: The addition of concomitant and adjuvant TMZ to hypofractionated RT for elderly pts with GB significantly improves OS and PFS in all patients and is well tolerated. Patients with MGMT methylated tumors benefit the most from the addition of TMZ to RT where median OS is nearly doubled. Clinical trial information: NCT00482677.

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