A phase 3 trial showed that for patients with high-grade glioma (HGG), treatment with armodafinil did not show a meaningful benefit in reducing cancer-related fatigue. Results of the trial were recently published in JAMA Oncology.

Fatigue is a common symptom for patients with HGG. Armodafinil is a central nervous system stimulant that had been associated with statistically significant improvements in fatigue in patients with glioma in prior studies. Therefore, a phase 3 trial was conducted to determine its efficacy vs a placebo in patients with HGG.

In this trial (ClinicalTrials.gov Identifier: NCT01781468), adult patients with grade 3 or 4 glioma were stratified by sex, age, and other treatments and randomly assigned to receive either armodafinil or placebo. Armodafinil was given at a dose of either 150 mg or 250 mg. Treatment was given for 8 weeks following assignment, or until unacceptable toxicity or a patient’s decision to discontinue.

Continue Reading

Outcomes in this study were based on self-reports with fatigue and other quality-of-life questionnaires. Cognition was also evaluated. The primary study objective was determining efficacy in terms of treating fatigue, with either armodafinil dose or the placebo, and multiple secondary objectives were also explored. The primary endpoint was the proportion of patients achieving a clinically meaningful improvement in patient-reported fatigue.

There were 328 patients enrolled in the trial, and treatment was completed by 195 patients. Discontinuations were reported in 18% of patients in the armodafinil, 150 mg arm; 17% in the armodafinil, 250 mg arm; and 18% in the placebo arm. Discontinuations related to adverse events were reported in 8% of patients receiving 150 mg of armodafinil, 14% of those receiving 250 mg of armodafinil, and 4% of those receiving placebo.

A statistically significant difference in clinically meaningful improvement in fatigue was not seen in this study from baseline to week 8. Among patients receiving 150 mg of armodafinil, 28% (95% CI, 20%-38%) achieved a clinically meaningful improvement, compared with 28% (95% CI, 19%-38%) with 250 mg of armodafinil, and 30% (95% CI, 21%-40%) with placebo (P =.94).

Patients receiving 250 mg of armodafinil more often experienced insomnia, compared with patients receiving either 150 mg of armodafinil or placebo. Headache was the most common symptom reported by patients; 40% of patients receiving 150 mg of armodafinil, 47% of patients receiving 250 mg of armodafinil, and 35% of patients receiving placebo reported headache.

“The phase 3 randomized clinical trial was unable to identify any meaningful benefit of armodafinil at either dose for treating fatigue in patients with high-grade glioma,” the study investigators concluded.

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Porter AB, Liu H, Kohli S, et al. Efficacy of treatment with armodafinil for cancer-related fatigue in patients with high-grade glioma: a phase 3 randomized clinical trial. JAMA Oncol. Published online December 9, 2021. doi:10.1001/jamaoncol.2021.5948