Modafinil to Improve Fatiguability (MODIFY)

Ottawa Hospital Research Institute

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: Modafinil; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05333250

663439

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 2 patient groups, including a placebo group

Modafinil

Experimental group

Description:

Two 100mg modafinil capsules once daily for 2 weeks

Treatment:

Drug: Modafinil

Placebo

Placebo Comparator group

Description:

Two 100mg placebo capsules once daily for 2 weeks

Treatment:

Other: Placebo