Modafinil to reduce fatigue and thinking problems in advanced cancer
Modafinil to Improve Fatiguability (MODIFY): Modafinil vs. Placebo Vanguard RCT
This project tests whether modafinil helps people with advanced cancer who have significant fatigue and related thinking problems.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Ottawa Hospital Research Institute Academic / other |
| Drugs / interventions | chemotherapy, prednisone |
| Locations | 1 site (Ottawa, Ontario) |
| Trial ID | NCT05333250 on ClinicalTrials.gov |
What this trial studies
This Vanguard randomized, placebo-controlled phase 1/2 trial at The Ottawa Hospital compares modafinil with placebo in adults with stage III or IV cancer experiencing clinically significant cancer-related fatigue. Participants are randomized to receive modafinil or matching placebo and are followed to measure changes in fatigue severity and cognitive function while collecting feasibility data such as recruitment and retention. Key inclusion criteria include age ≥18, ECOG 0–2, prognosis ≥3 months, and an ESAS-r-cs fatigue score ≥4, and key exclusions include recent cytotoxic chemotherapy, severe liver dysfunction, and contraindications to modafinil. The trial aims to estimate effect sizes for fatigue and cognitive outcomes and determine whether a larger definitive trial is feasible.
Who should consider this trial
Good fit: Adults (≥18) with stage III–IV cancer, ECOG 0–2, prognosis of at least 3 months, English-speaking, able to consent, and reporting significant fatigue (ESAS-r-cs fatigue ≥4).
Not a fit: Patients who recently received cytotoxic chemotherapy, have severe liver dysfunction, low hemoglobin, uncontrolled thyroid abnormalities, or an allergy to modafinil are excluded and likely will not benefit from this study intervention.
Why it matters
Potential benefit: If successful, modafinil could reduce persistent fatigue and improve attention and thinking for some patients with advanced cancer.
How similar studies have performed: Modafinil has been tested previously for cancer-related fatigue and daytime sleepiness with mixed results—some small trials showed benefit but findings are not definitive.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Ottawa, Ontario
- The Ottawa Hospital — Ottawa, Ontario, Canada (Recruiting)
Study contacts
- Principal investigator: Edward Fitzgibbon, MD, MSc, CCFP(PC) — The Ottawa Hospital
- Study coordinator: Shainuka Kannathas, HBSc
- Email: shkannathas@ohri.ca
- Phone: (613) 562-6262
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.