Clinical trial NCT05333250: Modafinil to Improve Fatiguability
Official title: Modafinil to Improve Fatiguability (MODIFY): Modafinil vs. Placebo Vanguard RCT
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Cancer-related Cognitive Difficulties
Cancer-related Problem/Condition
Fatigue
Keywords: Cancer
Fatigue
Cognitive Impairment
Modafinil
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: The Ottawa Hospital
name: Bruyere Research Institute
First posted: 2022-04-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Stage III or IV cancer diagnosis;
* Has been off cytotoxic chemotherapy for at least 6 weeks;
* Eastern Cooperative Oncology Group (ECOG) score of 0-2;
* Experiencing CRF, defined as score of 4 or greater on the Fatigue item of the Edmonton Symptom Assessment System-revised (ESAS-r);
* Prognosis of at least 3 months;
* Able to understand and communicate in English and/or French;
* Able to give first-person informed consent.

Exclusion Criteria:

* Allergy to modafinil;
* Dose change of prednisone or dexamethasone in the past 7 days or planned dose change during study period;
* Received blood transfusion in the past 2 weeks;
* Hemoglobin lower than 80 g/L measured within 2 weeks of enrolment;
* Thyroid Stimulating Hormone (TSH) above normal range (measured within 2 weeks or start date);
* Patients with known brain metastasis or primary brain tumors;
* Documented dementia diagnosis;
* Documented major psychiatric illness including major depressive episode, bipolar disorder, or schizophrenia;
* Uncontrolled hypertension, defined as blood pressure higher than 140/80;
* Inability to ingest oral capsule;
* Pregnant or lactating;
* Severe liver dysfunction, defined as newly developed liver enzyme elevation total bilirubin \>3 upper limits of normal, aspartate aminotransferase or alanine aminotransferase \>5 upper limits of normal.

Primary outcomes:
measure: Fatigue
timeFrame: 2 weeks
measure: Fatigue
timeFrame: 2 weeks
measure: Recruitment rate
timeFrame: 2 years
measure: Completion of intervention
timeFrame: 2 years
measure: Completion of follow-up
timeFrame: 2 years
Secondary outcomes:
measure: Cognition
timeFrame: 2 weeks
measure: Quality of Life
timeFrame: 2 weeks
measure: Adverse events
timeFrame: 2 weeks
measure: Patient satisfaction with MFI
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
Study officials:
affiliation: The Ottawa Hospital
name: Edward Fitzgibbon, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: The Ottawa Hospital
name: James Downar, MDCM, MHSc
role: PRINCIPAL_INVESTIGATOR
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