NCT06648902

Safety and Preliminary Efficacy of Meldonium in Patients with Metastatic Renal Cell Carcinoma and Treatment-associated Fatigue

A Phase 1/2 Study of the Safety and Preliminary Efficacy of Meldonium in Patients with Metastatic Renal Cell Carcinoma and Treatment-associated Fatigue.

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: Kidney Cancer Research Bureau · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Fatigue is a prevalent adverse event associated with systemic therapy using tyrosine kinase inhibitors (TKIs). Meldonium, a fatty acid oxidation inhibitor, modifies the carnitine pathway, a nutrient critical for fat metabolism. The World Anti-Doping Agency (WADA) classified meldonium as a banned substance due to its documented use by athletes aiming to enhance physical performance. In this study, the safety and preliminary efficacy of meldonium in treatment-related fatigue will be assessed.

Detailed description

Fatigue is a frequent symptom of cancer and the most common adverse event of treatment with tyrosine kinase inhibitors. For example, in phase 2 randomized study 59% of patients with metastatic renal cell carcinoma experienced any grade fatigue during treatment with the combination of lenvatinib and everolimus. Fourteen percent of patients had grade 3 fatigue or asthenia. Fatigue was also most frequently reported treatment-related adverse event in patients with unresectable hepatocellular carcinoma (30%), and advanced thyroid cancer (60%) treated with lenvatinib. Additionally, fatigue is one of the most common adverse events associated with the administration of checkpoint inhibitors. Frequency of fatigue was 55% in patients with endometrial cancer treated with combination of pembrolizumab and lenvatinib. Meldonium is a fatty acid oxidation inhibitor, and it is now principally used for heart conditions, such as angina, heart attack, heart failure, and others. The compound works by altering pathways for carnitine, a nutrient involved in fat metabolism. Meldonium received the greatest fame in sport. The World Anti-Doping Agency (WADA) added meldonium to their list of banned substances in 2016 because of evidence of its use by athletes with the intention of enhancing performance. Center for Preventive Doping Research and European Monitoring Center for Emerging Doping Agents showed that mildronate demonstrates an increase in endurance performance of athletes, improved rehabilitation after exercise, protection against stress, and enhanced activations of the central nervous system functions. Based on these data, meldonium can be a possible option in cancer patients with fatigue treated with targeted or imminotargeted therapy. Moreover, the compound could decrease the number of vascular adverse events of TKIs.

Conditions

• Renal Cell Cancer Metastatic
• Kidney Cancer
• Fatigue Related to Cancer Treatment

Interventions

Type	Name	Description
DRUG	meldonium	500 mg (Arm A) or 1,000 mg (Arms B and C) orally daily, weeks 1-6

Timeline

• Start date: 2022-02-01
• Primary completion: 2024-09-01
• Completion: 2024-09-01
• First posted: 2024-10-18
• Last updated: 2024-10-18

Locations

3 sites across 3 countries: Albania, Azerbaijan, Russia