E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Fatigue caused by cancer or its treatment |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016256 |
E.1.2 | Term | Fatigue |
E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
What is the clinical effectiveness of methylphenidate versus placebo for cancer-related fatigue in patients receiving palliative care? |
|
E.2.2 | Secondary objectives of the trial |
1. What are the effects of methylphenidate (versus placebo) on quality of life; mood; and activities of daily living in patients receiving palliative care?
2. What are the adverse effects of methylphenidate (versus placebo) in patients receiving palliative care? |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Aged 18 years or over 2. Participant is willing and able to give informed consent for participation 3. Advanced incurable cancer of all tumour types 4. Moderate or severe fatigue (>3/10 on a numerical rating scale) 5. Able and willing to comply with all study requirements, including ability to participate in study for ten weeks 6. Participant is receiving generalist or specialist palliative care 7. Willing to allow his or her General Practitioner to be notified of participation in the study
|
|
E.4 | Principal exclusion criteria |
1. Pregnancy 2. Females of childbearing potential and males who have sexual partners with child-bearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; true abstinence) from the time consent is signed until 6 weeks after treatment discontinuation and inform the trial if pregnancy occurs. For the purpose of clarity, true abstinence is when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence, withdrawal, spermicides only or lactational amenorrhoea method for the duration of a trial, are not acceptable methods of contraception) 3. Females of childbearing potential must have a negative pregnancy test seven days or fewer prior to first dose administration and must be willing to have a pregnancy test at every physical visit during the study 4. Females must not be breastfeeding 5. Known sensitivity to methylphenidate or to any of the excipients 6. History of glaucoma 7. Known phaechromocytoma 8. Planned general anaesthesia in the next nine weeks 9. During treatment with non-selective, irreversible monoamine oxidase (MAO) inhibitors, or within a minimum of 14 days of discontinuing those drugs 10. Clinical Hyperthyroidism or thyrotoxicosis. Patients must have a thyroid function test (T4 and TSH) showing no evidence of hyperthyroidism in three months prior to first dose administration of study medication 11. Known diagnosis or history of severe depression, anorexia nervosa/anorexic disorders, suicidal tendencies, psychotic symptoms, severe mood disorders, mania, schizophrenia, psychopathic/borderline personality disorder 12. Known diagnosis or history of severe and episodic (Type 1) bipolar (affective) disorder (that is not well controlled) 13. Known pre-existing cardiovascular disorders including severe hypertension (BP >160/100mmHg), uncontrolled heart failure uncontrolled angina, arterial occlusive disease, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction (within last one year), potentially life-threatening arrhythmias and channelopathies 14. Pre-existing cerebrovascular disorders, cerebral aneurysm, vascular abnormalities including vasculitis or stroke (within last one year) or known high risk factors for cerebrovascular disorders 15. Current or previous psycho-stimulant use in last month 16. Severe anaemia (Haemoglobin < 80g/L) 17. Platelets <50 × 103/μL 18. White blood count less than 1.5 x 109/litre 19. Any evidence of severe or uncontrolled infection that in the view of the investigator makes it undesirable for the patient to participate in the trial 20. Estimated glomerular filtration rate [eGFR] <45 ml/minute per 1·73 m² 21. ALT > 2 x ULN or bilirubin > 1.5 x ULN 22. Participating in another research study involving any investigational agents within four weeks prior to registration 23. Insufficient English language skills to understand study documentation and complete assessments 24. Current treatment with clonidine, warfarin, monoamine oxidase inhibitors or modafinil 25. History of previous or current substance or alcohol dependency within the last one year 26. Unable to swallow tablets/capsules 27. History of poorly controlled epilepsy, or seizures related to underlying brain tumour 28. Any other significant disease or disorder which, in the opinion of the Investigator, may put the participant at risk or affect the participant’s ability to take part in the study
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome is fatigue at 6 weeks measured by the fatigue sub-scale of Functional Assessment of Chronic Illness Therapy (FACIT-F). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary outcomes are other measures of quality of life (using European Organisation for Research and Treatment of Cancer core Quality of Life Palliative Care questionnaire [EORTC QLQ-C15-PAL] and the EuroQol EQ-5D 5 level [EQ-5D-5L]), adverse events, activities of daily living; appetite; satisfaction of patients and carers; survival and need for other medication. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 16 |