Effect of cannabioids on the survival of glioblastoma: a phase II multicenter randomized clinical trial

Abstract

BACKGROUND: glioblastoma multiforme is the most common primary malignant tumor of the central nervous system in adults. In our environment, the incidence is 4.17 (95% CI 3.80- 4.57) cases per 100.000 inhabitants/year, with a global survival per year of 61%, 26.5% at two years and less than 5% after 5 years. It is considered an “orphan” treatment disease; the treatment is very palliative and seeks to control tumor growth and not progress. This has not changed since 2005, the year in which Stupp, R., et al. showed that the concomitance of chemotherapy and radiotherapy after surgery increased survival. In preclinical and clinical studies it has been seen that cannabinoids have antitumor effects, altering the growth, invasion and angiogenesis of cancer cells, which could be an advance in the prognosis of this tumor. An increase in endogenous cannabinoid levels has been seen in patients with glioblastoma as well as increased expression of cannabinoid receptors. OBJECTIVE: demonstrate that the one-year overall survival rate increases at least 20% by adding cannabinoids to the base treatment (Stupp regimen) with good tolerance, in addition to delaying the time to progression, compared to those patients who only receive the standard treatment. DESIGN: the study will be a multicenter, longitudinal, prospective, double-blind, randomized and controlled clinical trial. It will be carried out in the 3 cancer hospitals of Institut Català d'Oncologia. The one in Girona will be the coordinator center. INTERVENTION AND METHODS: subjects of the study will be those newly diagnosed glioblastoma patients who, after resection, begin medical treatment. They will be randomly divided into two groups: group A (n = 30), patients will be treated with the classic scheme plus concomitant cannabinoids during chemotherapy and radiotherapy until progression; in group B (n = 29), patients will receive the same Stupp scheme plus concomitant placebo treatment instead of cannabinoids. Recruitment of patients will last 12 months, with subsequent follow-up for 24 months