Medicinal Cannabis for symptom burden in children with advanced cancer

The trial will commence with a two-week baseline observation period, where measurements relating to symptom burden will be measured. Participants will then be randomised to one of two-arms to receive combinations of Tetrahydrocannabinol (THC) and Cannabidiol (CBD) oral cannabis oil. Doses will be titrated upwards over two weeks, to a dose where symptom relief with tolerable side effects is achieved (as measured by clinical assessment and the 32 item Memorial Symptom Assessment Scale (MSAS) Global Distress Index). This will be followed by a four week maintenance phase on a stable dose as determined by the 2-week titration period. Blood will be drawn for pharmacokinetic and biomarker analysis at week -1 (week prior to commencement of intervention), week 2 of dose titration, and week 6 of intervention (end of 4-week maintenance phase). Symptom burden will be measured at weekly clinic appointments through the trial using the Memorial Symptom Assessment Scale. Confirmed documented disease will be assessed at days 14 and 28, 42 and 56 (where applicable). Participants wishing to access medicinal cannabis beyond the clinical trial period will be able to do so via the Special Access Scheme B. Patients not wishing to continue use of medicinal cannabis will have the product slowly titrated down over a one week period at the end of the clinical trial. Participants will be contacted at day 86 (+ 4 weeks post last dose) for the purposes of safety follow up and recording of post-study medicinal cannabis use. Arm 1: THC: CBD Equivalent Investigational Product, with a 1:1 ratio of 10 mg THC and 10 mg CBD per mL in an oral MCT oil vehicle (Little Green Pharma). This Investigational Product will be upwardly titrated during a two-week Dose Titration Phase from 0.1mg/0.1mg/kg/day to a maximum of 1 mg/1 mg/kg/day, with a maximum possible dose of 20 mg of THC and 20 mg CBD per day (0.1mL/kg/day to a maximum of 2mL per day). This dose will be given in two divided doses. The two-week Dose Titration Phase will be followed by a four-week maintenance phase with the maintenance dose being determined by the two-week titration phase. Arm 2: CBD-Dominant Investigational Product with with a ratio of THC to CBD of 1:100. This Investigational Product contains CBD and THC at 100 mg/mL and 1 mg/mL respectively in an oral solution (Little Green Pharma). This will be upwardly titrated in the two-week Dose Titration Phase, with a dose range of CBD 1 mg/kg/day and THC 0.01mg/kg/day, up to a maximum of 200 mg/kg/day of CBD and 2 mg/kg/day of THC. The maximum possible dose is 200 mg of CBD and 2 mg of THC per day (0.1 mL/kg/day to a maximum dose of 2ml). This dose will be given in two divided doses. The two-week Dose Titration Phase will be followed by a four-week maintenance phase with the maintenance dose being determined by the two-week titration phase. Dose/day (mL/kg) Titration Sechedule for Arm 1 and Arm 2 Investigational Products Day 1 0.005 mL/kg, to a max of 0.1 mL Day 2 0.01 mL/kg, to a max of 0.2 mL Day 3 0.02 mL/kg, to a max of 0.4 mL Day 4 0.025 mL/kg, to a max of 0.5 mL Day 5 0.03 mL/kg, to a max of 0.6 mL Day 6 0.04 mL/kg, to a max of 0.8 mL Day 7 0.045 mL/kg, to a max of 0.9 mL Day 8 0.05 mL/kg, to a max of 1.0 mL Day 9 0.06 mL/kg, to a max of 1.2 mL Day 10 0.065 mL/kg, to a max of 1.3 mL Day 11 0.07 mL/kg, to a max of 1.4 mL Day 12 0.08 mL/kg, to a max of 1.6 mL Day 13 0.085 mL/kg, to a max of 1.7 mL Day 14 0.09 mL/kg, to a max of 1.8 mL Day 15 0.1 mL/kg, to a max of 2 mL Dose/day (mL/kg) Weaning Schedule for Arm 1 and Arm 2 Investigational Products Day 1 0.09 mL/kg, to a max of 1.8 mL Day 2 0.085 mL/kg, to a max of 1.7 mL Day 3 0.08 mL/kg, to a max of 1.6 mL Day 4 0.07 mL/kg, to a max of 1.4 mL Day 5 0.065 mL/kg, to a max of 1.3 mL Day 6 0.06 mL/kg, to a max of 1.2 mL Day 7 0.05 mL/kg, to a max of 1.0 mL Day 8 0.045 mL/kg, to a max of 0.9 mL Day 9 0.04 mL/kg, to a max of 0.8 mL Day 10 0.03 mL/kg, to a max of 0.6 mL Day 11 0.025 mL/kg, to a max of 0.5 mL Day 12 0.02 mL/kg, to a max of 0.4 mL Day 13 0.01 mL/kg, to a max of 0.2 mL Day 14 0.005 mL/kg, to a max of 0.1 mL Day 15 0 mL/kg - No dose given Adherence to the trial drug will be monitored weekly by checking the volume of Investigational Product used/remaining each week, documentation of spillage of Investigational Product, completion of participant study diary and analysis of participant blood and urine samples. Participants will be required to return and unused or spoilt Investigational Products and empty bottles to their respective clinical trial pharmacy.