Modafinil to Improve Fatiguability

NCT ID: NCT05333250

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-22
• Study Completion Date: 2028-03-31

Brief Summary

Cancer-related fatigue (CRF) and cancer-related cognitive impairment (CRCI) are among the most commonly reported disabling symptoms experienced by patients with advanced cancer. However, there are currently limited evidence-based pharmacologic interventions available. The investigators will conduct a Vanguard Randomized Clinical Trial (RCT) to estimate the effect of modafinil in managing CRF and CRCI, and to test the feasibility of carrying out the study.

Detailed Description

Background:

Patients with advanced cancer often experience various disabling symptoms. Cancer-related fatigue (CRF) and cancer-related cognitive impairment (CRCI) are among the most common reported symptoms, yet the availability of evidence-based pharmacologic interventions is limited.

CRF can be defined as a "distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning." CRF is experienced by over 75% of patients with advanced cancer.

CRCI is defined as a decline in one or more areas of cognitive function, including attention and concentration, executive functioning, information processing speed, language, visuospatial skill, psychomotor ability, and memory. It is estimated that up to 40% of patients experience CRCI prior to any treatment; up to 75% during their treatment; and up to 60% upon completion of therapies.

Modafinil is a psychostimulant that has been studied in the context of CRF and daytime sleepiness. Its mechanism of action is not clear, but it is thought to promote wakefulness through dopaminergic neurotransmission which has been hypothesized to play a role in CRF.

Study Hypothesis:

Modafinil will improve CRF and CRCI

Study Objectives:

1. To estimate the effect size of modafinil in managing CRF and CRCI

2. To test the feasibility of carrying out the study (recruitment, etc.)

Study Design:

Randomized, placebo-controlled, double-blind, single-centre vanguard trial

Sample Size & Study Population:

Approximately 40 outpatients presenting ≥4/10 on the fatigue score of their screening questionnaire will be recruited. Eligible patients must be 18-75 years old with advanced cancer who have not received cytotoxic chemotherapy for at least one month.

Intervention:

Subjects will be randomized to receive 200 mg of modafinil or placebo once daily for one week.

Study Outcome Measures:

Using validated questionnaires and a digital tool, the investigators will assess the patient's fatigue (CRF), cognition (CRCI), and quality of life before and after the intervention. In addition, patients will report their global impression of change.

Finally, if patients experience any adverse events (headache, nausea, vomiting, anxiety, etc.), they will report them using a standard questionnaire. Adverse events (AEs) and Serious Adverse Events (SAEs) will be documented.

Expected Outcomes:

Positive results should provide justification to prolong the study to complete a phase III trial. This study is important because fatigue remains a cause of suffering amongst palliative patients with cancer. Modafinil has the potential to improve patients' fatigue, cognition, and quality of life.

Conditions

Cancer-related Cognitive Difficulties; Cancer-related Problem/Condition; Fatigue

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Modafinil

Two 100mg modafinil capsules once daily for 2 weeks

Group Type: EXPERIMENTAL

Modafinil

Intervention Type: DRUG

Modafinil

Placebo

Two 100mg placebo capsules once daily for 2 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Interventions

Modafinil

Modafinil

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

Other Intervention Names

Provigil

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Ottawa Hospital

OTHER

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edward Fitzgibbon, MD, MSc, CCFP(PC)

Role: PRINCIPAL_INVESTIGATOR

The Ottawa Hospital

James Downar, MDCM, MHSc

Role: PRINCIPAL_INVESTIGATOR

The Ottawa Hospital

Locations

The Ottawa Hospital

Ottawa, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Shainuka Kannathas, HBSc

Role: CONTACT

shkannathas@ohri.ca

(613) 562-6262 ext. 2354

Facility Contacts

Shainuka Kannathas, HBSc

Role: primary

shkannathas@ohri.ca

613-562-6262 ext. 2354

References

Berger AM, Mooney K, Alvarez-Perez A, Breitbart WS, Carpenter KM, Cella D, Cleeland C, Dotan E, Eisenberger MA, Escalante CP, Jacobsen PB, Jankowski C, LeBlanc T, Ligibel JA, Loggers ET, Mandrell B, Murphy BA, Palesh O, Pirl WF, Plaxe SC, Riba MB, Rugo HS, Salvador C, Wagner LI, Wagner-Johnston ND, Zachariah FJ, Bergman MA, Smith C; National comprehensive cancer network. Cancer-Related Fatigue, Version 2.2015. J Natl Compr Canc Netw. 2015 Aug;13(8):1012-39. doi: 10.6004/jnccn.2015.0122.

Reference Type: BACKGROUND

PMID: 26285247 (View on PubMed)

Jansen CE, Cancer Basics J, Eggert I (eds) (2010) Pittsburgh, PA:oncology nursing. Society

Reference Type: BACKGROUND

Wefel JS, Kesler SR, Noll KR, Schagen SB. Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults. CA Cancer J Clin. 2015 Mar;65(2):123-38. doi: 10.3322/caac.21258. Epub 2014 Dec 5.

Reference Type: BACKGROUND

PMID: 25483452 (View on PubMed)

Murillo-Rodriguez E, Barciela Veras A, Barbosa Rocha N, Budde H, Machado S. An Overview of the Clinical Uses, Pharmacology, and Safety of Modafinil. ACS Chem Neurosci. 2018 Feb 21;9(2):151-158. doi: 10.1021/acschemneuro.7b00374. Epub 2017 Dec 4.

Reference Type: BACKGROUND

PMID: 29115823 (View on PubMed)

Hovey E, de Souza P, Marx G, Parente P, Rapke T, Hill A, Bonaventura A, Michele A, Craft P, Abdi E, Lloyd A; MOTIF investigators. Phase III, randomized, double-blind, placebo-controlled study of modafinil for fatigue in patients treated with docetaxel-based chemotherapy. Support Care Cancer. 2014 May;22(5):1233-42. doi: 10.1007/s00520-013-2076-0. Epub 2013 Dec 17.

Reference Type: BACKGROUND

PMID: 24337761 (View on PubMed)

Other Identifiers

663439

Identifier Type: -

Identifier Source: org_study_id