Olanzapine for weight gain in children undergoing chemotherapy for solid-organ malignancies: An investigator-initiated, open-label, multicenter, phase III randomized controlled trial (SNOWMAN).

10053 Background: Children receiving intensive chemotherapy for solid-organ malignancies frequently experience deterioration in nutritional status. Olanzapine improves nutritional outcomes in adults with advanced cancer and is guideline-endorsed. Its use in pediatric oncology has been limited by safety concerns and lack of robust data. We conducted this trial to evaluate the efficacy and safety of olanzapine for weight gain in children undergoing chemotherapy for solid-organ malignancies. Methods: In this open-label, investigator-initiated, multicenter, phase III randomized trial (CTRI/2024/03/064371), children aged 2-18 years with newly diagnosed solid-organ malignancies were randomized 1:1 to receive olanzapine (1.25-2.5 mg once daily, weight-based) plus standard dietary counseling (SDC) or SDC alone for 12 weeks, stratified by nutritional status. The primary endpoint was the proportion of participants achieving ≥5% weight gain at 12 weeks. Secondary endpoints included changes in appetite scores (visual analog scale), anorexia-related quality of life (QoL) (Peds-FAACT), anthropometric measures (weight, body-mass index, and mid-upper arm circumference), dietary intake, health-related QoL (PedsQL Cancer Module v3.0), and safety outcomes (CTCAE v5.0). Exploratory endpoints included longitudinal changes in body composition, using air-displacement plethysmography and skeletal muscle mass assessed by computed-tomography derived L3-L4 psoas muscle area. Results: A total of 130 participants were randomized (median age of 11.1 years; 13.9% undernourished), of whom 117 (60 olanzapine plus SDC, 57 SDC) had evaluable outcomes. At 12 weeks, 21/60 (35%) in olanzapine plus SDC and 22/57 (38.6%) in SDC group achieved the primary endpoint, with no significant difference between groups (OR 0.86, 95% CI 0.40-1.82; p=0.69). Longitudinal analyses showed no significant differences between groups in appetite scores, anthropometric measures, dietary intake, and QoL. Exploratory analyses showed no differential impact on skeletal muscle mass or fat proportions. Rates of grade ≥3 adverse events were similar between groups. No extrapyramidal symptoms were observed, and no participant required dose modification or discontinuation of olanzapine due to sedation or QTc prolongation. Conclusions: The addition of olanzapine to SDC does not increase the proportion of children achieving clinically meaningful weight gain over 12 weeks. The impact of pharmacological nutritional modulation may be limited by the physical hurdles posed by highly intensive pediatric chemotherapy protocols. Olanzapine was well tolerated and these data provide reassurance regarding its short-term safety for other supportive care indications in pediatric oncology. Clinical trial information: CTRI/2024/03/064371.