Canna~Fangled Abstracts

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

By February 24, 2021February 25th, 2021No Comments
Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM).
. 2021 Feb 24.

doi: 10.1038/s41416-021-01259-3.

Online ahead of print.
Chris Twelves 1 2, Michael Sabel 3, Daniel Checketts 4, Sharon Miller 4, Bola Tayo 4, Maria Jove 1, Lucy Brazil 5, Susan C Short 6 7, GWCA1208 study group
Collaborators, Affiliations 

Abstract

Background: Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM). Safety and preliminary efficacy of nabiximols oromucosal cannabinoid spray plus dose-intense temozolomide (DIT) was evaluated in patients with first recurrence of GBM.

Methods: Part 1 was open-label and Part 2 was randomised, double-blind, and placebo-controlled. Both required individualised dose escalation. Patients received nabiximols (Part 1, n = 6; Part 2, n = 12) or placebo (Part 2 only, n = 9); maximum of 12 sprays/day with DIT for up to 12 months. Safety, efficacy, and temozolomide (TMZ) pharmacokinetics (PK) were monitored.

Results: The most common treatment-emergent adverse events (TEAEs; both parts) were vomiting, dizziness, fatigue, nausea and headache. Most patients experienced TEAEs that were grade 2 or 3 (CTCAE). In Part 2, 33% of both nabiximols- and placebo-treated patients were progression-free at 6 months. Survival at 1 year was 83% for nabiximols- and 44% for placebo-treated patients (p = 0.042), although two patients died within the first 40 days of enrolment in the placebo arm. There were no apparent effects of nabiximols on TMZ PK.

Conclusions: With personalised dosing, nabiximols had acceptable safety and tolerability with no drug-drug interaction identified. The observed survival differences support further exploration in an adequately powered randomised controlled trial.

Clinical trial registration: ClinicalTrials.gov: Part 1- NCT01812603; Part 2- NCT01812616.

References

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