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Annals of Oncology
Conclusions: TH-302 demonstrates good tolerability when combined with
bevacizumab. The MTD has not been reached and only one grade 3/4 toxicity was
observed. Dose escalation is ongoing, with planned expansion at the MTD.
Disclosure: J. Sun: The author is an employee of pharmaceutical industry with a
financial interest in the drug which is the subject of this abstract. C. Hart: The
author is an employee of pharmaceutical industry with a financial interest in the
drug which is the subject of this abstract. C. Eng: The author is an employee of
pharmaceutical industry with a financial interest in the drug which is the subject of
this abstract. All other authors have declared no conflicts of interest.
437TiP A RANDOMISED PHASE II STUDY OF CARBOPLATIN AND
BEVACIZUMAB IN RECURRENT GLIOBLASTOMA
MULTIFORME (CABARET STUDY). COOPERATIVE TRIALS
GROUP FOR NEURO-ONCOLOGY (COGNO)
K. Field1 , M.A. Rosenthal1 , H. Wheeler2 , L. Cher3 ,E.Hovey4 , A.K. Nowak5 ,
C. Brown6 , A. Livingstone6 , K. Sawkins6 , R.J. Simes6 1
Department of Medical Oncology, Royal Melbourne Hospital, Parkville, VIC,
AUSTRALIA, 2 Medical Oncology, Royal North Shore Hospital, Sydney, NSW,
AUSTRALIA, 3 Neuro-Oncology, Austin Hospital, Melbourne, VIC, AUSTRALIA,
4
Medical Oncology, Prince of Wales Hospital, Sydney, NSW, AUSTRALIA,
5
Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA, AUSTRALIA,
6
Clinical Trials, NH&MRC Clinical Trials Centre, University of Sydney, Sydney,
NSW, AUSTRALIA
Background: Glioblastoma (GBM) is the most aggressive malignant glial tumor.
There is no accepted standard management after disease progression. Much remains
unknown about the optimal use of bevacizumab (bev), including the role of
continuing beyond progression, and patterns of radiological progression during and
after use. In addition, the new Response Assessment in Neuro-Oncology (RANO)
criteria have yet to be validated prospectively.
Methods: This study is a multi-centre, stratified randomised phase II trial. Patients
have recurrent GBM after radiotherapy and temozolomide, have had no other
chemotherapy for GBM, and have ECOG performance status 0–2. At least three
months have elapsed since radiotherapy. In Part 1, patients are randomised 1:1 to
intravenous bev 10 mg/kg 2-weekly and carboplatin AUC5 4-weekly or bev
monotherapy. On progression, eligible patients are randomised to continue or cease
bev (Part 2). The primary objective is to determine the effect of bev plus carboplatin
versus bev alone on progression-free survival according to modified RANO criteria.
Secondary endpoints are response rates, cognitive function, quality of life, steroid
dose, toxicity, and overall survival. CogState, a validated neurocognitive testing
system, is being used prospectively for the first time in this population and compared
with mini-mental state examination. Exploratory endpoints include biomarker
analyses, comparison of modified RANO and modified MacDonald criteria,
predictive value of early MRI after 2 doses of bev, steroid dosing, and location and
type of radiological progression during and after therapy.
Results: Enrolment commenced in Nov 2010, completing Part 1 accrual in Mar 2012
with 122 patients randomised from 17 Australian sites. Randomisation to Part 2
continues. Feasibility and safety data will be presented; efficacy outcome results are
not expected until 2013.
Conclusions: The study results will significantly improve knowledge regarding the
use of bevacizumab in the setting of recurrent GBM, as well as providing for the first
time a prospective analysis of CogState neurocognitive testing for patients with brain
tumours.
Disclosure: M.A. Rosenthal: Roche Advisory Board member. H. Wheeler: Roche
Advisory Board member. E. Hovey: Roche Advisory Board member. A.K. Nowak:
Roche Advisory Board member and has received research funding through Roche
Australia. R.J. Simes: Roche Advisory Board Member. All other authors have
declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds394 | ix151