CANnabinoids in Pediatric ONCology

This is a multi-centered, pragmatic, double-blind, adaptive, dose-escalation study to establish the tolerability of Cannabis Herbal Extracts (CHE) containing different ratios of delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Study arms will contain the following ratios THC:CBD 1:25 (arm 1), 1:5 (arm 2) and 1:1 (arm 3). CAN-PONC will enroll 20 participants recruited into each arm, for a total of 60 study participants.

To inform the dose for the arm containing the most THC, this study will take place in two stages. In Stage One: The first 20 participants will be randomized 1:1 into arm 1 and arm 2. Once 20 participants have been recruited, trial recruitment will halt until the last participant reaches the maintenance phase, the maximum THC dose at which less than 30% of participants reported dose limiting toxicities (Max-D30) has been established, the remaining 40 recruited participants will be randomized 1:1:2 into arm 1, arm 2 and arm 3 in Stage Two of this study.

All arms consist of three phases: baseline phase (no interventional product for two weeks), treatment phase (dose escalations for eight weeks), and a maintenance phase (maximum tolerated dose for four weeks).

Inclusion criteria

• Ages 4-17 years old at the time of enrollment
• Diagnosed with relapsed or refractory solid or hematologic malignancy including brain tumours
• Currently receiving active cancer treatment or supportive and palliative care
• Estimated survival of at least 4 months at the time of enrollment

Exclusion criteria

• History of cardiovascular disease, severe hepatic or renal impairment defined by alanine transaminase (ALT)/ aspartate aminotransferase (AST) more than 5x upper limit of normal (ULN), creatinine more than 5x ULN or glomerular filtration rate (GFR less than) <60 mL/min/1.73 m273m2, unstable/unmanaged arrhythmias, uncontrolled hypertension with blood pressure above 99th centile for age or history of myocardial infarction
• Nabilone or other cannabis-based products use (including for recreational purposes) within the past 2 weeks or planned nabilone use for the duration of their enrollment in the trial. Current use/continued use of recreational cannabis, or not willing to abstain from recreational cannabis use during the trial
• Anyone who is pregnant or breast/chest-feeding throughout the duration of the study or has the intention to become pregnant within 3 months of study completion
• Participation in other clinical trials that prohibit the concurrent use of cannabis
• Children with a personal or family history of schizophrenia or psychotic disorders, substance use disorder or allergy to cannabinoids or cannabis
• Unwilling or unable to use effective form of contraception and refrain from driving motorized vehicles (cars, motorcycles, boats, etc.) throughout the study period
• Anyone who is currently receiving cell therapies or immune checkpoint inhibitors