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Cancer-related Cognitive DifficultiesPhase 1/2MODIFYNCT05333250

Modafinil to Improve Fatiguability

A Phase 1/2 study testing Modafinil in people with Cancer-related Cognitive Difficulties and Cancer-related Problem/Condition, run by Ottawa Hospital Research Institute at 1 site in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Modafinil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
1 siteCanada
Study dates
16 Mar 2026to Mar 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 years of age or older with stage III or IV cancer diagnosis
  • Estimated prognosis ≥ 3 months
  • Eastern Cooperative Oncology Group (ECOG) Score 0-2
  • 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)
  • Ability to understand and communicate in English
  • Ability to give first-person informed consent

Who cannot join

  • 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
Show all 37Show fewer
  • 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:
  • Methylphenidate
  • Cyclosporine
  • Propranolol
  • Phenytoin
  • S-mephenytoin
  • Warfarin
  • Triazolam
  • Ethinyl estradiol
  • Clomipramine
  • Midodrine
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Shainuka Kannathas, HBSc contact

(613) 562-6262 ext. 2354

shkannathas@ohri.ca

Canada1 site, 1 recruiting

  • The Ottawa Hospital

    Ottawa, Ontario

    Shainuka Kannathas, HBSc, 613-562-6262 ext. 2354, shkannathas@ohri.ca

    Edward Fitzgibbon, MD, MSc, CCFP(PC)

    Recruiting

Other trials in Canada

About this study

Official title: Modafinil to Improve Fatiguability (MODIFY): Modafinil vs. Placebo Vanguard RCT

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.

Read the 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.

Being tested
Modafinil, Placebo
Keywords
Cancer, Fatigue, Cognitive Impairment, Modafinil
Medical subject headings
Fatigue, Neoplasms, Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ModafinilDrug

    Also called Provigil

    Modafinil

  • PlaceboOther

    Placebo

Study groups in NCT05333250
Study groupRoleWhat they receive
ModafinilExperimentalTwo 100mg modafinil capsules once daily for 2 weeks
Receives: Drug: Modafinil
PlaceboPlacebo comparatorTwo 100mg placebo capsules once daily for 2 weeks
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fatigue

    Change in fatigue score evaluated using Multidimensional Fatigue Inventory (MFI).

    Measured: 2 weeks

  2. Fatigue

    Change in fatigue score evaluated using Patient's Global Impression of Change (PGIC) score.

    Measured: 2 weeks

  3. Recruitment rate

    The number of patients approached, total participants screened for eligibility, and reason for ineligibility or refusal to participate will be documented. We will consider the study successful if we can enroll 40 participants over a 2-year study period, with a recruitment rate of 15%.

    Measured: 2 years

  4. Completion of intervention

    We will consider the intervention to be feasible if at least 75% of enrolled participants complete the full intervention protocol.

    Measured: 2 years

  5. Completion of follow-up

    We will consider the intervention to be feasible if at least 75% of enrolled participants complete all assessments at 1-week follow-up.

    Measured: 2 years

Secondary outcomes (4)

  1. Cognition

    Change in cognition score evaluated using the Fast Cognitive Evaluation (FaCE).

    Measured: 2 weeks

  2. Quality of Life

    Change in quality of life score evaluated using McGill Quality of Life Questionnaire-Revised (MQOL-R).

    Measured: 2 weeks

  3. Adverse events

    Daily patient-reported adverse effects with specific focus on headache, nausea and vomiting and anxiety, evaluated using the Common Terminology Criteria for Adverse Events (CTCAE).

    Measured: 2 weeks

  4. Patient satisfaction with MFI

    Patient satisfaction with MFI as a measure of their fatigue on a 5-point Likert scale.

    Measured: 2 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2022
  2. Study start16 Mar 2026
  3. Primary completionOct 2027 (estimated)
  4. Study completionMar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05333250
Sponsor's protocol ID
663439
Acronym
MODIFY
Status last verified
Jul 2026
First submitted
5 Apr 2022
Last updated
27 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 26285247

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

  • 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.

    PubMed 25483452

  • 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.

    PubMed 29115823

  • 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.

    PubMed 24337761

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Modafinil in people with Cancer-related Cognitive Difficulties and Cancer-related Problem/Condition, run by Ottawa Hospital Research Institute at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Shainuka Kannathas, HBSc ((613) 562-6262 ext. 2354, shkannathas@ohri.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fatigue (time frame: 2 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05333250, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.

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