Inclusion Criteria:
1. 18 years of age or older with stage III or IV cancer diagnosis
2. Estimated prognosis ≥ 3 months
3. Eastern Cooperative Oncology Group (ECOG) Score 0-2
4. Experiencing cancer-related fatigue, defined as a score of 4 or greater on the Fatigue item of the Edmonton Symptom Assessment System-revised-constipation/sleep (ESAS-r-cs)
5. Ability to understand and communicate in English
6. Ability to give first-person informed consent
Exclusion Criteria:
- Currently receiving or have received cytotoxic chemotherapy in the last 6 weeks
- Allergy to modafinil or placebo contents
- Dose change of prednisone or dexamethasone in the past 7 days or planned dose change during study period
- Blood transfusion in the last 2 weeks
- Hemoglobin lower than 80 g/L measured in the last 4 weeks
- TSH above normal range in the last 4 weeks
- Severe liver dysfunction (total bilirubin >3x upper limit of normal, or aspartate aminotransferase or alanine aminotransferase >5x upper limit of normal)
- Known brain metastasis or primary brain tumor
- Documented dementia diagnosis
- Documented major psychiatric illness including major depressive episode, bipolar disorder, schizophrenia
- Uncontrolled hypertension as defined by a blood pressure greater than 140/90mmHg
- Unstable angina
- Recent (<6 months previous) myocardial infarction
- Evidence of left ventricular hypertrophy or ischemia on ECG
- Arrythmia (e.g., atrial fibrillation)
- Coronary artery disease with Canadian Cardiovascular Society Symptoms Class >1
- Taking high dose selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants
- Taking any benzodiazepine at any dose
- Taking any amphetamine at any dose
- Taking any monoamine oxidase inhibitor (MAOI) at any dose
- Taking any azole anti-fungal medication (e.g., fluconazole, itraconazole, or ketoconazole)
- Taking any of the following medications at any dose:
1. Methylphenidate
2. Cyclosporine
3. Propranolol
4. Phenytoin
5. S-mephenytoin
6. Warfarin
7. Triazolam
8. Ethinyl estradiol
9. Clomipramine
10. Midodrine
11. Antipyrine
- Inability to ingest oral capsule
- Pregnancy or lactation, or trying to conceive
- Any other history, condition, therapy, or uncontrolled intercurrent illness which could, in the opinion of the Qualified Medical Investigator, affect compliance with study requirements or which would make the participant unsuitable for this study.
- Simultaneous participation in another interventional clinical study (e.g., Phase 1-3 clinical studies) or treatment with any investigational medicinal product within 30 days prior to screening visit that could, in the judgment of the Qualified Medical Investigator, affect the patient's participation in or outcome of this clinical trial.