A phase III placebo controlled randomized controlled trial using combination therapy for treatment-related fatigue in patients with prostate cancer.

12005 Background: To determine if the combination of exercise (EX) plus methylphenidate (MP) is superior to EX plus placebo (PL) for 12 weeks in the treatment of cancer-related-fatigue (CRF) in patients with prostate cancer receiving androgen deprivation therapy (ADT) and/or radiation therapy (RT). Methods: Using a phase III randomized double-blind placebo-controlled design, we assessed treatments combining either EX or its stretching (ST) control with either MP (5mg twice a day, with dose titrated up to 20mg a day) or placebo. Patients were eligible if they had prostate cancer patients who are receiving androgen deprivation therapy and/or radiation therapy and had CRF; Eligible patients were randomized into one of four arms, EX + MP, EX + PL, ST + MP, ST + PL (2:1:1:1). Primary outcome was assessed using linear mixed-effects model comparing the differences in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores at Weeks 1, 2, 4, 8 and 12. Results: 161 eligible patients were randomly assigned to 4 arms EX+MP (n = 65), EX+PL(n = 34), ST+MP (n = 30), and ST+PL (n = 32). Demographics, including mean age (65-67 years) were similarly distributed between arms (all p > 0.05). Bone metastases (~25%), and treatment modality distributions (ADT alone, ADT + RT, or RT alone) were comparable among the arms. The baseline FACIT-F scores [mean (SD) were 28.5(11.0), 28.7(8.9), 28.5(9.3), and 30.3(11.0)] respectively in arms EX+MP, EX+PL, ST+MP, and ST+PL arms. All 4 arms showed CRF improvement over time. There was a nonsignificant improvement in CRF in the EX+MP intervention arm, compared with EX+PL arm [FACIT-F coefficient, 2.73(95% CI, –0.49 to 5.96); P = 0.097]. Methylphenidate-containing arms (EX+MP and ST+MP) significantly improved CRF compared with their placebo counterparts (EX+PL and ST+PL), [FACIT-F coefficient, 3.23 (95% CI 0.84 to 5.63), P = 0.008]. There were no significant differences in CTCAE v.5 grade ≥3 adverse events by arms (P > 0.99). Conclusions: EX+MP arm was not superior to EX+PL arm in improvement of CRF. Methylphenidate-containing arms significantly improved CRF compared with their placebo arms. All four treatment arms showed improvement of CRF overtime suggesting strong placebo response. Further methylphenidate-containing multimodal CRF studies are needed. Clinical trial information: NCT03772834 .