Effect of multimodal intervention care on cachexia in patients with advanced cancer compared to conventional management (MIRACLE): An open-label, parallel, randomized, phase 2 trial.

Abstract

e24135 Background: Cancer Cachexia (CC) is a multi-factorial process characterized by progressive weight loss, muscle mass and fat tissue wasting, and adversely affecting their quality of life and survival in patients with advanced stage of cancer. We investigated the efficacy and safety of a multi-modal intervention including anti-inflammation, omega-3-fatty acids, nutritional supplement with counselling, physical exercise, psychiatric intervention as well as Bojungikki-tang which mediates immune-modulation and reverse chronic inflammation and wasting condition as a complementary and alternative medicine compared to patients receiving best supportive care. Methods: Eligible criteria included patients with advanced stage of gastrointestinal (gastric, colorectal and pancreaticobiliary) as well as lung cancer undergoing active palliative chemotherapy. Patients are randomized into experimental arm (Multi-modal intervention care: MIC) versus control arm (Conventional Palliative Care, CPC). MIC are comprised of daily oral medications; ibuprofen 400 mg three times a day, omega-3-fatty acid 1 g twice a day, Bojungikki-tang 3.75g twice a day, oral nutritional supplement (HAMONILAN SOLN) 200 ml twice a day, and weekly physical exercise (60 minutes per visit), psychiatric assessment on every other week, and nutritional counselling total four times during the study period. CPC included basic nutritional counselling for two times provided by National Health Insurance Service, and megestrol acetate as needed (ie, anorexia≥grade 2). All interventions were provided during 12 weeks per subject. Co-primary outcomes are total lean body mass changes and handgrip strength change from the baseline. Secondary outcomes included change of fat mass and total body mass, lean body mass, and quality of life assessment (KCT0004967, NCT 04907864). Results: A total of 112 patients was planned to be assigned to the two arms (56 in each group), however, the study was terminated due to low accrual rate and the expiration of the study approval period of the national research fund, after enrolling up to 56 subjects (28 in each group). Demographic findings were even distributed between arms. The difference of median changes of total lean body mass in MIC group after 12 weeks of intervention, was numerically increased without statistical significance compared to CPC group (MIC vs CPC, 91 vs. -295 g, p= 0.3863). There was no difference of median changes of handgrip strength between MIC and CPC groups (MIC vs CPC, 0.4 vs. 0.9, p= 0.2319). Other secondary outcomes showed no differences, either. Conclusions: Multimodal intervention in this study did not show clinical meaningful improvement. We have to further investigate another method to improve cachexia. Clinical trial information: NCT04907864 .