Cancer-related Cognitive Difficulties, Cancer-related Problem/Condition, Fatigue
Conditions
Keywords
Cancer, Fatigue, Cognitive Impairment, Modafinil
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.
Interventions
DRUGModafinil
Modafinil
OTHERPlacebo
Placebo
Sponsors
Ottawa Hospital Research Institute
The Ottawa Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue | 2 weeks | Change in fatigue score evaluated using Multidimensional Fatigue Inventory (MFI). |
| Recruitment rate | 2 years | 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%. |
| Completion of intervention | 2 years | We will consider the intervention to be feasible if at least 75% of enrolled participants complete the full intervention protocol. |
| Completion of follow-up | 2 years | We will consider the intervention to be feasible if at least 75% of enrolled participants complete all assessments at 1-week follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognition | 2 weeks | Change in cognition score evaluated using the Fast Cognitive Evaluation (FaCE). |
| Quality of Life | 2 weeks | Change in quality of life score evaluated using McGill Quality of Life Questionnaire-Revised (MQOL-R). |
| Adverse events | 2 weeks | 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). |
| Patient satisfaction with MFI | 2 weeks | Patient satisfaction with MFI as a measure of their fatigue on a 5-point Likert scale. |
Countries
Canada
Contacts
CONTACTShainuka Kannathas, HBSc
PRINCIPAL_INVESTIGATOREdward Fitzgibbon, MD, MSc, CCFP(PC)
The Ottawa Hospital
PRINCIPAL_INVESTIGATORJames Downar, MDCM, MHSc
The Ottawa Hospital
Outcome results
None listed