CANnabinoids in Pediatric ONCology

Study Overview
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Brief Summary
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CANnabinoids in Pediatric ONCology is a randomized, double blind, adaptive clinical trial looking at the tolerability of cannabinoids in children with cancer across 3 Canadian children's hospitals.

Detailed Description
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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).

Official Title
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A Randomized, Double-Blind Tolerability Trial of Cannabinoids for Symptom Management in Children With Cancer: the CAN-PONC Trial

Conditions
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Cancer, Childhood Cancer

Intervention / Treatment
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* Drug: MPL-001
* Drug: MPL-005
* Drug: MPL-009


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 4-18 years old at the time of enrollment Diagnosed with relapsed or refractory solid or hematologic malignancy Currently receiving active cancer treatment or 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 ALT/AST more than 5x ULN, creatinine more than 5x ULN or GFR >60, unstable/unmanaged arrhythmias, uncontrolled hypertension with blood pressure above 99%ile 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 throughout the study period

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1. High-CBD arm (MPL-001)<br>High-CBD arm (MPL-001) a cannabidiol-enriched cannabis herbal extract which contains a 1:25 ratio of THC:CBD. | Drug: MPL-001<br>* High-CBD arm (MPL-001) a cannabidiol-enriched cannabis herbal extract which contains a 1:25 ratio of THC:CBD. The MPL-001 oil is produced by MediPharm Labs, each ml contains 50mg CBD and 2mg THC.<br>|
| Experimental: Arm 2. Medium-CBD arm (MPL-005)<br>Medium-CBD arm (MPL-005) a cannabidiol-enriched cannabis herbal extract which contains a 1:5 ratio of THC:CBD. | Drug: MPL-005<br>* Medium-CBD arm (MPL-005) a cannabidiol-enriched cannabis herbal extract which contains a 1:5 ratio of THC:CBD. The MPL-005 oil is produced by MediPharm Labs, each ml contains 25mg CBD and 5mg THC.<br>|
| Experimental: Arm 3. Balanced arm (MPL-009)<br>Balanced arm (MPL-009) a balanced 1:1 ratio of THC:CBD. | Drug: MPL-009<br>* Balanced arm (MPL-009) a balanced 1:1 ratio of THC:CBD. The MPL-009 oil is produced by MediPharm Labs, each ml contains 25mg CBD and 25mg THC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (Tolerability) | Reported through study completion | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity | Pain will be measured using Faces Pain Scale-Revised reported by the participants daily throughout the study. Pain will be reported for each study visit as a percentage change from the weekly average documented at baseline. | daily for 14 weeks | 
| Symptom burden | Symptom burden is measured using the score of Symptom Screening in Pediatrics Tool (SSPedi) assessed three times a week throughout the study and will be reported as a weekly average and percentage change from baseline. | 3 times per week for 14 weeks | 
| Quality of life (child) | Pediatric quality of life inventory (PedsQLTM) will be assessed weekly throughout the study | once per week for 14 weeks | 
| Sleep (hours per night) | Sleep, will be reported as the number of hours per night, measured using Actigraphy and/or parent report, will be reported as an average over a one-week time period. | daily for 14 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CBD, cannabinoids, THC, pediatrics, cannabis