A Phase 2 Randomised, Double Blind Clinical Trial assessing the Tolerability of Two different Ratios of Medicinal Cannabis in patients with Glioblastoma multiforme (GBM)

INTERVENTION: Medicinal cannabis imported from overseas. NB: CBD is cannabidiol, THC is Delta‐9– tetrahydrocannabinol. The administration of this drug will be for 12 weeks per participant and it is an oil which will be ingested orally. The drug will be self administered or by a carer/family member/appointed person. Arm 1: Standard treatment[1] plus CBD:THC (1:1) (6mg/mL:6mg/mL) Arm 2: Standard treatment plus CBD:THC (1:4) (3.8mg/mL:15mg/mL) [1] Standard treatment is defined as chemotherapy, radiation, immunotherapy, or any other cancer related treatment requested by the participants medical specialists and including best supportive and palliative care. Dosing for this trial will start at 0.25 ml (of either arm 1 or 2 of the combined THC:CBD whole plant extract oil) of the oral medicinal cannabis oil per day and titrated up according to participant’s weight and symptoms. As oral ingestion has to be processed by the liver, effects will be slower than smoking or vaporizing of cannabis. It can take anywhere from 1‐1.5 hours for effects to be noticed and can take 2‐4 hours to reach its peak effect. Dose will start at 0.25mL at night. If the person is able to function normally the next day, the dose will be increased 0.3mL, if they were not able to function as normal, the dose will be decreased to 0.2mL next night. Each night, the dose will either go up or down by 0.05mL depending on how the participant feels. The research nurse/assistant will be phoning the participant each morning to assess how the person is feeling to determine if they should titrate up or down or stay at that dose. Previous trials on oral administration of medicinal cannabis have shown that dose escalation or titration is best choice for the participants. Previous trials, although not on patients with cancer have documented the first dose as 2.7mg THC:2.5mg CBD. These trials increased a dose every 2‐3 hours over 24 to 48 hour period till the person felt they were affected by the dose. The dose is then stabilized at that amount for that person and the dose documented. The maximum dose documented in this trial was 48 administrations over 24 hour period. Adherence or fidelity will be assessed by blood pathology tests for THC and CBD levels in the blood at 4 weeks, 8 weeks and 12 weeks. The blood pathology results will be assessed by the primary investigator and the research team. If there is poor adherence or fidelity, the research team will contact the participant to inquire about taking the dose. CONDITION: Glioblastoma multiform PRIMARY OUTCOME: Changes in quality of life (QoL) as quantified by the FACT‐Br between the two medicinal cannabis groups from baseline (week 0) to 12 weeks. ; Costs that will be measured include conventional standard care costs, both prescribed medications, chemotherapy, radiation, consultation fees etc. These costs will be calculated based on whole costs including both to government to the individual. However, full cost to individual such as lost time at work, waiting time will not be included in this calculation. Treatment related toxicity. [Time frame: monthly for 12 weeks] Treatment related toxicity will be according to NCI CTC Version 4.0. This will be recorded throughout the treatment. A patient with a grade 3 or more treatment related toxicity or adverse events will be taken off the study and appropriate medical attention and intervention provided. INCLUSION CRITERIA: Diagnosis: Recurrent Glioblastoma multiforme (GMB) 1. Have been diagnosed with a recurrent brain malignancy (GBM): MRI revealing recurrent tumour growth 2. Greater than or equal to 18 years of age 3. Patient status: a) Liver function: Total bilirubin less than or equal to 2 ULN, ALT or AST is less than or equal to 2.5 ULN (or less than 5 in case of liver impairment). SECONDARY OUTCOME: Analysis the absorption of the oral medicinal cannabis oil (THC and CBD concentrations) in by analysis of CBD and THC levels from blood pathology tests. Assess the difference of response rate to two different cannabinoid ratio dosages using the RANO criteria, Assessing the difference of response rate to the two different cannabinoid ratio dosages on Tumour measurements according to the RANO criteria from MRI results (ie. sum of products of diameters (SPD). At 12 weeks, participants will be categorised based on their SPD (ie. change in SPD (from baseline to 12 weeks) is =25% or <25%). Changes in blood pathology markers within the blood. (FBC, ELFT, THC, CBD) Changes in quality of life (QoL) as quantified by the FACT‐Br between the two medicinal cannabis groups every 4 weeks from baseline (week 0) to 12 weeks (T0, T4, T8, T12). Cost effectiveness will be assessed via the QoL measure ‐ FACT‐Br. * Recurrent Cancer Definition: Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrence. (National Cancer Institute Dictionary for Cancer) b) Serum creatinine is less than or equal to 1.5 ULN 4. Willing to consider participating in a clinical trial using oral medicinal cannabis 5. Diagnosis of recurrent tumour progression 6. Individuals who have no history of substance abuse