Condition category
Cancer
Date applied
17/07/2017
Date assigned
10/08/2017
Last edited
14/05/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information

Type

Public

Primary contact

Dr Elli Enayat

ORCID ID

http://orcid.org/0000-0002-5765-9047

Contact details

Marie Curie Palliative Care Research Department
Division of Psychiatry
University College London
6th Floor
Maple House
149 Tottenham Court Road
London
W1T 7NF
United Kingdom

Additional identifiers

EudraCT number

2017-001950-33

ClinicalTrials.gov number

Protocol/serial number

34827

Study information

Scientific title

Methylphenidate versus placebo for fatigue in advanced cancer (MePFAC)

Acronym

Study hypothesis

The study aims to estimate clinical effectiveness of methylphenidate versus placebo in the treatment of cancer-related fatigue in patients receiving specialist palliative care.

Ethics approval

London - City & East Research Ethics Committee, 07/08/2017, ref: 17/LO/0871

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Specialty: Cancer, Primary sub-specialty: Psychosocial Oncology and Survivorship; UKCRC code/ Disease: Cancer/ Malignant neoplasms of ill-defined, secondary and unspecified sites

Intervention

MePFAC is a Prospective, randomised, double-blind, placebo-controlled trial with internal pilot in palliative care patients with advanced cancer.
The MePFAC study aims to recruit 230 patients across ten sites in England between 2018 and 2020. Feasibility of recruitment strategy, randomisation and follow-up are evaluated during a pilot phase at four sites during the first nine months of recruitment.

Randomisation is undertaken using an independent data management company (“Sealed Envelope”) who have been commissioned by the Priment Clinical Trials Unit to support randomisation and data management for the MePFAC study. Treatment allocation (1:1) is done using a permuted-block randomisation stratified to four factors; the centre, receipt of palliative cancer treatment, baseline HADS depression score, and whether patients are considered to be “severely” fatigued (initial fatigue score >7/10 on a numerical rating scale).

In both trial arms participants are monitored on a weekly basis either by telephone contact (weeks 1, 2, 4, 5, 7 & 8) or at a face-to-face visit (weeks 0, 3, 6 & 9).

Participants in both arms are prescribed identical looking tablets of either methylphenidate 5mgs or placebo. At weekly intervals (± 3 days) after study medication has been dispensed, participants are contacted by telephone (weeks 1, 2, 4, 5, 7 and 8) or face-to-face (weeks 3, 6 and 9) and the study medication (or placebo) are titrated by the PI in response to information provided by the research staff.

Study medication is dispensed at the baseline assessment, week 3 (± 3 days) and week 6 (± 3 days). The three days’ flexibility on either side of the scheduled assessment days is to allow for contingencies. On visit days, pill counts are performed to assess compliance to IMP.

At the face-to face assessment at the end of week 9 (±3 days) the study will end. At that point participants are assessed by the local clinical service and a decision is made about whether or not methylphenidate should be prescribed depending upon local clinical assessment and patient and physician preference.

Intervention type

Drug

Phase

Drug names

Methylphenidate

Primary outcome measures

To compare fatigue, measured by Functional Assessment of Chronic Illness Therapy (FACIT-F), in patients with advanced cancer receiving individually titrated doses of methylphenidate with patients receiving placebo after six weeks’ treatment.

Secondary outcome measures

1. Quality of life is measured using the 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]) at 3, 6 and 9 weeks
2. Adverse events are documented on the case report form (as mild, moderate or severe) at 3, 6 and 9 weeks
3. Activities of daily living is measured using the mobility, self-care and usual activity domains of the EQ-5D-5L at 3, 6 and 9 weeks
4. Appetite is measured using the anorexia item on the EORTC QLQ-C15-PAL at 3, 6 and 9 weeks
5. Satisfaction of patients and carers are measured using the Global benefit score (GBS) at 3, 6 and 9 weeks
6. Survival of patients after recruitment is measured by asking patients for permission to flag their records with the NHS Information Centre (NHS IC) at 3, 6 and 9 weeks
7. Need for other medication specifically steroids, antidepressants, anxiolytics and analgaesics) will be measured by asking participants about concomitant medication use at baseline and at week six

Overall trial start date

01/05/2017

Overall trial end date

21/10/2020

Reason abandoned

Eligibility

Participant 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. Prognosis 2-12 months (as estimated by clinician)
6. Able and willing to comply with all study requirements, including ability to participate in study for nine weeks
7. Under the care of a specialist palliative care team
8. Willing to allow his or her General Practitioner to be notified of participation in the study

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 230; UK Sample Size: 230

Participant exclusion criteria

1. Females of childbearing potential and males 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)
2. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment.
3. Females must not be breastfeeding.
4. Known sensitivity to methylphenidate or to any of the excipients.
5. History of glaucoma
6. Known phaechromocytoma
7. Planned general anaesthesia in the next nine weeks
8. During treatment with non-selective, irreversible monoamine oxidase (MAO) inhibitors, or within a minimum of 14 days of discontinuing those drugs
9. Hyperthyroidism or thyrotoxicosis
10. Known diagnosis or history of severe depression, anorexia nervosa/anorexic disorders, suicidal tendencies, psychotic symptoms, severe mood disorders, mania, schizophrenia, psychopathic/borderline personality disorder
11. Known diagnosis or history of severe and episodic (Type 1) Bipolar (affective) disorder (that is not well controlled)
12. Known pre-existing cardiovascular disorders including severe hypertension (BP > 160/100mmHg), heart failure, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias and channelopathies
13. Pre-existing cerebrovascular disorders, cerebral aneurysm, vascular abnormalities including vasculitis or stroke or known risk factors for cerebrovascular disorders
14. Current or previous psycho-stimulant use in last month
15. Severe anaemia (Haemoglobin < 80g/L)
16. Platelets < 50 × 103/μL
17. White blood count > 30 × 109/L
18. Estimated glomerular filtration rate [eGFR] < 60 ml/minute per 1·73 m²
19. Liver function tests elevated > 3 x upper limit of normal (either ALT > 165 U/L; or AST > 144 U/L; or ALP > 345 U/L; or GGT > 144 U/L; or Bilirubin > 3.6mg/dL)
20. Currently an inpatient in a hospital or a hospice
21. Currently participating in another research study involving an investigational product
22. English not first language or unable to read English
23. Current treatment with clonidine, warfarin, monoamine oxidase inhibitors or modafinil
24. History of previous or current substance or alcohol abuse
25. Unable to swallow tablets/capsules
26. History of poorly controlled epilepsy, or seizures related to underlying brain tumour
27. 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

We will not exclude patients who are still receiving tumour-directed therapies (e.g. chemotherapy or radiotherapy) provided that the treatment is with palliative intent and that the expected prognosis is 2 – 12 months. We believe that to exclude such patients would make recruitment very difficult and would also mean that the study population was not representative of the broader palliative care population (in whom disease modifying treatments are frequently used up until a few weeks or months before death). Nonetheless we will stratify patients by whether or not they are in receipt of disease-modifying treatment as this may be expected to affect their fatigue levels one way or another.

Recruitment start date

15/01/2018

Recruitment end date

31/03/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University College London Hospital
University College London Hospitals NHS Foundation Trust 250 Euston Road
London
NW1 2PG
United Kingdom

Trial participating centre

Martlets Hospice
Wayfield Avenue
Hove
BN3 7LW
United Kingdom

Trial participating centre

Brighton General Hospital
Sussex Community NHS Foundation Trust, Elm Grove East Sussex
Brighton
BN2 3EW
United Kingdom

Trial participating centre

Leeds Community Healthcare NHS Trust
Leeds Community, Healthcare NHS Trust Stockdale House 8 Victoria Road West Yorkshire
Leeds
LS6 1PF

Trial participating centre

Marie Curie Hospice
Hampstead 11 Lyndhurst Gardens
London
NW3 5NS
United Kingdom

Trial participating centre

Pilgrims Hospices
56 London Road
Canterbury
CT2 8JA
United Kingdom

Trial participating centre

Stephenson House
Central And North West, London NHS Foundation Trust 75 Hampstead Road
London
NW1 2PL
United Kingdom

Trial participating centre

LOROS
Groby Road
Leicester
LE3 9QE
United Kingdom

Trial participating centre

Nottinghamshire Healthcare NHS Foundation Trust
The Resource Duncan Macmillan House Porchester Road
Nottingham
NG3 6AA
United Kingdom

Trial participating centre

Queens Medical Centre
Nottingham University Hospitals NHS Trust Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Leckhampton Court Hospice
Church Road
Leckhampton
GL53 0QJ
United Kingdom

Sponsor information

Organisation

University College London

Sponsor details

Joint Research Office
Charlene Griffith
PRIMENT Clinical Trials Unit
UCL Medical School
Royal Free Campus
London
NW3 2PF
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Plans are unknown at this stage, however, the aim is to publish the study results in a high-impact peer reviewed journal in October 2021. All proposed publications will be accord with UCL publication policy.

IPD sharing statement:
The datasets generated and analysed during the current study will be available upon request from Professor Paddy Stone, p.stone@ucl.ac.uk. IPD will be accessible after the main publications.

Intention to publish date

31/10/2021

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Editorial Notes

14/05/2018: Internal review. 16/01/2018: Internal review. 11/08/2017: Uploaded protocol Version 3 19 July 2017 (not peer reviewed)