Evaluation of Dronabinol and Cannabidiol for Symptom Burden Reduction in Palliative Oncology Patients: A Randomized, Placebo-Controlled Trial

The primary objective of this study is to demonstrate the **improvement** of global symptom-burden in oncologic patients receiving palliative care, compared to a placebo control group. This will be assessed over a period of 12 ± 2 days using the Edmonton Symptom Assessment System total symptom distress score (ESAS TSDS). The clinical relevance of this objective lies in generating evidence for the use of Cannabis Extract Avextra 10/10 Solution in palliative oncology, potentially informing future clinical trials in this domain.

Secondary objectives include evaluating changes in the Global Patient’s Assessment (GPA), morphine-equivalent dosage, and the number and defined daily dosages of other indirect analgesic drugs. Additionally, the study will assess symptom changes using the ESAS-TSDS rating, changes in disappetence, and alterations in the NCCN-Distress-Thermometer, all measured at various time points compared to baseline.

The clinical trial involves a study population comprising both **male** and **female** participants aged 25 years and older. The participants are individuals undergoing **palliative-oncological therapy** with an Eastern Cooperative Oncology Group (ECOG) performance status of 1, 2, or 3, indicating they are unable to work. The trial does not include a vulnerable population. Participants are required to have a Nutritional Risk Screening score of 3 or higher and a pain numerical rating scale of 4 or higher. Additionally, the Edmonton Symptom Assessment System total symptom distress score (ESAS TSDS) must be 16 or higher. Women of childbearing potential must have a negative pregnancy test and use safe contraception with a Pearl Index of less than 1%. The total number of participants is not provided by the sponsor. The selection criteria ensure that the study population is representative of individuals experiencing significant symptom burden in a palliative oncology setting, with informed consent being a prerequisite for participation.

The clinical trial is designed to evaluate the **efficacy** of Cannabis Extract Avextra 10/10 Solution in improving the quality of life for patients undergoing palliative oncological therapy. This is a Phase 4, randomized, double-blind, placebo-controlled trial. The trial aims to assess the change in global symptom burden over a period of 12 ± 2 days, using the Edmonton Symptom Assessment System Total Symptom Distress Score (ESAS TSDS) as the primary endpoint. Secondary endpoints include various assessments such as the Global Patient’s Assessment, changes in opioid dosage, and quality of life measures.

Participants will be involved in the study for a maximum of 8 weeks, with the trial expected to conclude by April 30, 2026. The study will commence with a screening visit to confirm eligibility based on criteria such as age (25 years or older), ECOG status, and informed consent. Following successful screening, participants will be randomized to receive either the active treatment or placebo. Study visits will occur at baseline, during the treatment period, and at the end of the study to monitor safety and efficacy outcomes. The end-of-study visit will include a comprehensive assessment of all endpoints.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial will ensure rigorous monitoring of adverse events, coded according to the Medical Dictionary for Regulatory Activities (MeDRA) and evaluated using the NCI Common Terminology Criteria for Adverse Events (CTCAE). The study's findings are anticipated to provide evidence for the therapeutic use of the investigational product in palliative oncology and inform future research in this field.

The clinical trial involves the administration of **Cannabis Extract Avextra 10/10 Solution**, an **oral solution** formulated by Avextra Pharma GmbH. This experimental medication contains two active substances: **dronabinol** and **cannabidiol**, both of which are of chemical origin. Dronabinol, also known as **delta-9-tetrahydrocannabinol (THC)**, and cannabidiol (CBD) are administered in a combined formulation. The maximum daily dose is 24 mg, with a total treatment period of up to 8 weeks. The solution is administered orally, and participant compliance is monitored throughout the study to ensure adherence to the dosing schedule.

The study also includes a **placebo** control group, which receives the **Sesamöl-Leinöl-Mischung PL 01**. This mixture is administered orally, similar to the experimental treatment, to maintain consistency in the route of administration. The placebo is used to evaluate the efficacy of the Cannabis Extract Avextra 10/10 Solution by providing a baseline for comparison. The placebo does not contain any active substances and serves as a control to assess the improvement of global symptom-burden in oncologic patients.

Efficacy in the clinical trial titled "Improvement of Quality of Life by Cannabinoids in Oncologic Patients (BELCANTO)" will be assessed primarily through the **Edmonton Symptom Assessment System total symptom distress score (ESAS TSDS)**. The primary endpoint is the change in symptoms, measured as the change in the ESAS-TSDS rating after approximately 12 days compared to baseline, between the intervention group and the placebo group. This assessment aims to provide evidence for the use of Cannabis Extract Avextra 10/10 Solution in palliative oncology.

Secondary endpoints include a variety of measures to further evaluate efficacy. These include the Global Patient’s Assessment (GPA), changes in opioid dosage as morphine-equivalent dosing, and changes in the count and defined daily dosage of other analgesic drugs. Additional assessments involve changes in symptom scores, appetite, distress levels using the NCCN-Distress-Thermometer, pain levels using a numerical rating scale, and quality of sleep using the Pittsburgh Sleep Quality Index (PSQI). The trial will also assess changes in quality of life using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C15 PAL), and the appearance, frequency, and severity of adverse events coded according to the Medical Dictionary for Regulatory Activities (MeDRA) and evaluated following NCI Common Terminology Criteria for Adverse Events (CTCAE).

Furthermore, the trial will measure the absolute value and change in plasma concentration of C-reactive protein (CRP) compared to baseline, derived from routine samples according to standard-of-care. Stratified evaluations will be conducted based on the type and stage of the oncological disease, treatment method, sex, weight, dosage, and age. These comprehensive assessments will be conducted at various timepoints throughout the trial to ensure a thorough evaluation of the intervention's efficacy.