A Safety Study of Sativex Compared With Placebo (Both With Dose-intense Temozolomide) in Recurrent Glioblastoma Patients
An open-label phase to assess the frequency and severity of adverse events in recurrent glioblastoma patients receiving Sativex in combination with dose-intense Temozolomide (Part A). A randomisation phase to assess the safety of Sativex compared with placebo (Part B). Part B will be reported here.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Two Part Study to Assess the Tolerability, Safety and Pharmacodynamics of Sativex in Combination With Dose-intense Temozolomide in Patients With Recurrent Glioblastoma|
- Incidence of Adverse Events as a Measure of Patient Safety. [ Time Frame: Study Day 1 - Day 358 ] [ Designated as safety issue: Yes ]Adverse events will be coded according to the current medical dictionary for regular activities graded using the Common Terminology Criteria for Adverse Events criteria. The number of patients who experienced an adverse event whilst on treatment will be presented.
- The number of patients with Progression Free Survival at six months (PFS6) [ Time Frame: Study Day 1 - Day 190 ] [ Designated as safety issue: Yes ]PFS6 will be assessment at Visit 11 (Day 190). Progression of disease will be determined from Response Assessment in Neuro-Oncology tumour assessment (based on Magnetic Resonance Imaging scans). The number of patients with PFS6 will be presented for the individual treatment groups.
- Overall Survival [ Time Frame: Study Day 1 - Day 358 ] [ Designated as safety issue: Yes ]Overall survival will be assessed at the end of the treatment visit (Day 358 or at early termination). The number of surviving patients in each group from the randomisation phase (Part B) will be presented.
|Study Start Date:||September 2013|
|Estimated Study Completion Date:||October 2015|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: Sativex and Dose-Intense Temozolomide
Patients will received Sativex and Dose-Intense Temozolomide in a double-blind manner
Administered orally as a spray to the cheek according to a standard dose titration regimen, until patients reach a maximum tolerated dose (maximum 12 sprays per day). Each spray delivers 100 μl (Δ9tetrahydrocannabinol (THC), 27 mg/ml: Cannabidiol (CBD), 25 mg/ml).
Placebo Comparator: Placebo and Dose-Intense Temozolomide
Patients will received placebo and Dose-Intense Temozolomide and in double-blind manner
Administered orally as a spray to the cheek according to a standard dose titration regimen, until patients reach a maximum tolerated dose (maximum 12 sprays per day). Each spray delivers 100 μl ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring and Food, Drugs & Cosmetics (FD&C)certified color additives; FD&C Yellow No.5 (E102 tartrazine) (0.0260%), FD&C Yellow No.6 (E110 sunset yellow) (0.0038%), FD&C Red No. 40 (E129 Allura red AC) (0.00330%) and FD&C Blue No.1 (E133 Brilliant blue FCF) (0.00058%).
Other Name: Placebo comparator
Patients will receive Sativex and dose-intense Temozolomide in an open-label phase. The incidence of adverse events will be monitored (Part A). An investigator led Safety Review Team will assess the safety profile of the open-label patients and decide whether the study can progress to the randomisation phase (Part B). Patients who enrol in the randomisation phase patients will receive either Sativex or placebo. The safety of Sativex compared to placebo will be assessed by pharmacokinetic analysis of Temozolomide and its metabolites, clinical laboratory tests, adverse events and vital signs.
|Study Chair:||Susan Short, MD||Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Buidling, St James Univeristy Hospital, Leeds|
|Principal Investigator:||Christopher Twelves, MD||St James's Institute of Oncology, St James's University Hospital, Leeds.|
|Principal Investigator:||Lucy Brazil, MD||St. Thomas' Hospital, Clinical Oncology, London.|
|Principal Investigator:||Catherine McBain, MD||Dpt. Clinical Oncology, The Christie, Manchester.|
|Principal Investigator:||Brian Haylock, MD||The Clatterbridge Cancer Centre, Bebington, Wirral|