'Palliative-D' Vitamin D to Palliative Cancer Patients (Palliative-D)

PROTOCOL IDENTITY AND OBJECTIVES: EudraCT Number 2017-000268-14 Protocol Title: Vitamin D supplementation to palliative cancer patients - A double blind, randomised controlled trial. Acronym: "Palliative-D" Trial Objectives: To test the hypothesis that vitamin D treatment during 12 weeks to palliative cancer patients can decrease opioid consumption, fatigue and infectious burden and increase quality of life.

INVESTIGATIONAL MEDICINAL PRODUCTS (IMP): Test ProductDetremin, MA holder Renapharma; Pharmaceutical Form: Oil Route of Administration: Oral route

METHODOLOGY Trial Design: Double-blind, parallel randomised and placebo controlled trial Dose/Duration 4000 IU/day for 12 weeks

Primary Endpoint:

The decline of opioid-consumption during 12 weeks in the vitamin D group compared to the placebo group, based on 3 measurements with 4 weeks intervals.

Secondary end Points:

1. Decline in antibiotic consumption
2. Improvement in quality of life
3. Improvement in fatigue
4. Vitamin D levels in serum after 12 weeks
5. Association between opioid dose and genetic polymorphism in genes involved in the effect and metabolism of vitamin D in the body.

Efficacy Parameters:

Opioid dose, translated to fentanyl per hour measured at baseline and at week 4,8 and 12.

Antibiotic consumption expressed as % of days with antibiotics during the last 4 weeks measured at baseline and at week 4, 8 and 12.

Quality of Life measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks. Fatigue measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks. 25-hydroxyvitamin D levels in blood at baseline and after 12 weeks. ESAS (Edmonton Symptom Assessment Scale ) measured at baseline and at week 4, 8 and 12.

Safety Parameters: S-calcium will be controlled in all subjects at baseline, at week 4, 8 and 12 and U-calcium in selected cases Power: The least clinically meaningful effect is estimated to be a 20% decline in opioid dose compared to the placebo. To obtain this result with 80% power the number of patients is estimated to be 127 in each arm i.e. 254 patients in total. This includes a drop-out of 25% per group.

Statistical Analyse plan: The primary endpoint will be analysed using linear regression, using bias corrected and accelerated bootstrap confidence intervals, while controlling for baseline measure of opioid dose (similar to ANCOVA). Adjustment for other background variables - such as vitamin D-level at baseline, gender and age - will be made in a secondary analysis to gain efficiency. The continuous secondary endpoints will be analysed using the same method as the primary endpoint .

POPULATION OF TRIAL SUBJECTS Number of Subjects: 254 (127 vitamin D and 127 placebo) Description of Trial Subjects: Palliative Cancer Patients (any cancer form) with a life expectancy of more than 3 months.

TRIAL TIMETABLE First Subject In Aug 2017 Last Subject In Sept 2019 (25 months to include participants) Last Subject Out Dec 2019 End of intervention Dec 2019 End of follow up Dec2019 End of Trial: Dec 2020