A phase II randomized, double-blind, placebo-controlled study of Nuvastatic (C50SEW505OESA), a standardized rosmarinic acid-rich polymolecular botanical extract formulation to reduce cancer-related fatigue in patients with solid tumors

Aim We evaluated the efficacy and safety of Nuvastatic (TM) (C5OSEW5050ESA) in improving cancer-related fatigue (CRF) among cancer patients. Methods This multicenter randomized double-blind placebo-controlled phase 2 trial included 110 solid malignant tumor patients (stage II-IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic (TM) 1000 mg (N = 56) or placebo (N = 54) thrice daily for 9 weeks. The primary outcomes were fatigue (Brief Fatigue Inventory (BFI)) and Visual Analog Scale for Fatigue (VAS-F)) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration (an oxidative stress biomarker), Eastern Cooperative Oncology Group scores, adverse events, and biochemical and hematologic parameters. Analysis was performed by intention-to-treat (ITT). Primary and secondary outcomes were assessed by two-way repeated-measures analysis of variance (mixed ANOVA). Results The Nuvastatic (TM) group exhibited an overall decreased fatigue score compared with the placebo group. Compared with the placebo group, the Nuvastatic (TM) group significantly reduced BFI-fatigue (BFI fatigue score, F (1.4, 147) = 16.554, p < 0.001, partial eta(2) = 0.333). The Nuvastatic (TM) group significantly reduced VAS-F fatigue (F (2, 210) = 9.534, p < 0.001, partial eta(2) = 0.083), improved quality of life (QoL) (F (1.2, 127.48) = 34.07, p < 0.001, partial eta(2) = 0.243), and lowered urinary F2-IsoP concentrations (mean difference (95% CI) = 55.57 (24.84, 86.30)), t (55) = 3.624, p < 0.001, Cohen's d (95% CI) = 0.48 (0.20, 0.75)). Reported adverse events were vomiting (0.9%), fever (5.4%), and headache (2.7%). Conclusion Nuvastatic (TM) is potentially an effective adjuvant for CRF management in solid tumor patients and worthy of further investigation in larger trials. Trial registration ClinicalTrial.gov ID: NCT04546607. Study registration date (first submitted): 11-05-2020.