Table 1 Inclusion, exclusion, and withdrawal criteria

Inclusion criteria

1) Age over 18 years old diagnosed with advanced cancer undergoing active anticancer treatment

2) Patients diagnosed with any type of cancer except CNS tumor, hormone-sensitive cancers, or pheochromocytoma

3) CRF diagnosis based on the International Classification of Diseases 10th Edition (ICD-10)

4) Reporting of moderate to severe fatigue in the last week (score ≥ 4 on a scale of 0 to 10)

5) Hemoglobin level higher than 9 g/dL in 2 weeks before enrollment

6) Ability to swallow and absorb medications

7) In case of the possibility of getting pregnant during the treatment and up to 6 weeks after, willingness to use effective contraceptive methods

8) Ability to read and write

Exclusion criteria

1) Presence of a known fatigue disorder not related to cancer

2) Presence of cognitive disorders, mental disorders (severe anxiety, major depression, schizophrenia, bipolar syndrome), neurological or brain disorders (dementia, delirium, Tourette syndrome, motor tics, epilepsy, history of stroke, aneurysm), diabetes, untreated severe anemia or anemia that requires blood transfusion, severe and uncontrolled pain and insomnia, serious cardiac disorders, uncontrolled arrhythmia or hypertension, history of long QT syndrome, glaucoma, intestinal obstruction, uncontrolled hypothyroidism, respiratory disorders that limit participation, autoimmune diseases, bleeding disorders

3) Abnormal function of the liver (high ALT or AST) and kidney (abnormal Cr or GFR less than 50)

4) History of major surgery in 1 month before enrollment

5) Taking erythropoietin, psychostimulants, antidepressants, food supplements, or other drugs to control fatigue currently or in the 4 weeks before participating in the study

6) Simultaneous use of drugs (including warfarin, anticonvulsants, tricyclic antidepressants, antipsychotics, monoamine oxidase inhibitors, clonidine, theophylline, caffeine and pseudoephedrine)

7) Major dose change (more than 25%) of opioids in 48 h before enrollment

8) Hypersensitivity to sympathomimetic amines

9) Planned surgery within 2 months of screening

10) History of sensitivity to or intolerance of the medications under study

11) Pregnant or lactating women

12) History of drug or alcohol abuse in the past year

13) Involvement in other clinical trials

Withdrawal (discontinuation) criteria

1) Voluntary withdrawal of the trial by the patient for any reason

2) Significant deterioration in the patient’s clinical condition

3) Occurrence of severe/serious adverse event(s)

4) The need to take erythropoietin during the study period

5) Patient or doctor recognition that stopping the medications is in the patient’s best interest