A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma

SUPPLEMENTARY INFORMATION

ACKNOWLEDGEMENTS

AUTHOR CONTRIBUTIONS

Involved in analysis, interpretation of trial data, contributed to the writing and review of the manuscript: S.M., B.T., D.C. D.C. was responsible for the statistical analysis. Involved in the acquisition of trial data, interpretation of trial data and contributed to the writing and review of the manuscript: S.S., M.S., M.J., L.B. and C.T.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

This trial was conducted in accordance with International Council for Harmonisation Good Clinical Practice guidelines and ethical principles that have their origin in the Declaration of Helsinki. The research protocol was approved by the relevant Institutional Review Board or Independent Ethics Committee at each site, including: The NRES Committee Yorkshire & The Humber—Leeds East. The Ethics Committee of the State Medical Association of Thuringia in consultation with: The Ethics Committee of Friedrich-Alexander at the University of Erlangen-Nuremberg. The Ethics Committee of the Faculty of Medicine at the University of Duesseldorf. The Ethics Committee of the Faculty of Medicine at the Rheinisch-Westfälischen Technical College, Aachen. All patients provided written informed consent.

DATA AVAILABILITY

The trial protocol is registered on the ClinicalTrials.gov website (Part 1: NCT01812603; Part 2: NCT01812616). Supplemental Materials contain additional information about individual site and patient stopping rules, the safety review team, pharmacokinetic analysis, statistical methods, randomisation, patients excluded from the pharmacokinetic analysis, and Magnetic Resonance Imaging scans. Demographics and baseline characteristics are summarised in Supplemental Table 1. Maximum treatment-emergent adverse event toxicities for patients who experienced a grade 2 or higher treatment-emergent adverse event are summarised in Supplemental Table 2. EORTC-predicted vs. actual overall survival for the randomised element of the trial is summarised in Supplemental Table 3. EORTC-predicted vs. actual overall survival for the open-label element of the trial is summarised in Supplemental Table 4. Pharmacokinetic parameters for temozolomide and 4-amino-5-imidazole-carboxamide from the open-label element of the trial are summarised in Supplemental Table 5. Pharmacokinetic parameters for temozolomide and 4-amino-5-imidazole-carboxamide from the randomised element of the trial are summarised in Supplemental Table 6. The trial schema is supplied in Supplemental Fig. 1.

COMPETING INTERESTS

D.C., S.M. and B.T. are employed by and hold share options in GW. C.T., M.S., M.J., L.B. and S.S. have no conflicts of interest to declare.

FUNDING INFORMATION

The trial was sponsored by GW Research Ltd (GW). Medical writing support was provided to authors by Lesley Taylor, PhD, of Alchemy Medical Writing Ltd., and funded by Greenwich Biosciences, Inc. GW provided funding to the Leeds Hospital Clinical Fellowship program, which supported M.J.’s Fellowship. The Spanish Medical Oncology Society awarded a personal grant to M.J.

FOOTNOTES

CONTRIBUTOR INFORMATION

on behalf of the GWCA1208 study group:

REFERENCES