MePFAC - A Drug Trial for the treatment of cancer-related Fatigue

ISRCTN	ISRCTN79478762
DOI	https://doi.org/10.1186/ISRCTN79478762
EudraCT/CTIS number	2017-001950-33
IRAS number	215297
Secondary identifying numbers	CPMS 34827, IRAS 215297

Submission date: 17/07/2017
Registration date: 10/08/2017
Last edited: 04/07/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-a-drug-called-methylphenidate-for-people-with-tiredness-caused-by-cancer-mepfac

Contact information

Dr Elli Enayat
Public

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

ORCID ID	0000-0002-5765-9047
Phone	+44 20 7679 9269 (ext 09269)
Email	z.enayat@ucl.ac.uk

Prof Paddy Stone
Principal Investigator

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

Email	p.stone@ucl.ac.uk

Study information

Study design	Randomized; Interventional; Design type: Treatment, Drug
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	ISRCTN79478762_PIS_20July17_Screening_V4.pdf
Scientific title	Methylphenidate versus placebo for fatigue in advanced cancer (MePFAC)
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(s)	London - City & East Research Ethics Committee, 07/08/2017, ref: 17/LO/0871
Condition	Psychosocial Oncology and Survivorship
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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Methylphenidate
Primary outcome measure	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 study start date	01/05/2017
Overall study end date	31/10/2023

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 230; UK Sample Size: 230
Total final enrolment	162
Participant inclusion criteria	Current inclusion criteria as of 28/10/2018 (updated 27/07/2023): 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 Previous 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 exclusion criteria	Current exclusion criteria as of 28/10/2018 (updated 27/07/2023): 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 six 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 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 1 year) or known high-risk factors for cerebrovascular disorders 15. Current or previous psycho-stimulant use in the last month 16. Severe anaemia (haemoglobin <80g/L) 17. Platelets <50 × 10e3/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 1 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 Patients who are still receiving tumour-directed therapies (e.g. chemotherapy or radiotherapy) will not be excluded from the study provided that the treatment is with palliative intent. Patients will be stratified 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 (see Section 11.6). Previous 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	27/04/2023

Locations

Countries of recruitment

England
United Kingdom

Study participating centres

University College London Hospital

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

Martlets Hospice

Wayfield Avenue
Hove
BN3 7LW
United Kingdom

Brighton General Hospital

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

Leeds Community Healthcare NHS Trust

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

Marie Curie Hospice

Hampstead
11 Lyndhurst Gardens
London
NW3 5NS
United Kingdom

Pilgrims Hospices

56 London Road
Canterbury
CT2 8JA
United Kingdom

Stephenson House

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

LOROS

Groby Road
Leicester
LE3 9QE
United Kingdom

Nottinghamshire Healthcare NHS Foundation Trust

The Resource
Duncan Macmillan House
Porchester Road
Nottingham
NG3 6AA
United Kingdom

Queens Medical Centre

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

Leckhampton Court Hospice

Church Road
Leckhampton
GL53 0QJ
United Kingdom

Sponsor information

University College London
University/education

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

"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Government

National Institute for Health Research
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Results and Publications

Intention to publish date	31/12/2024
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
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 plan	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.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	version V4	20/07/2017	10/08/2017	No	Yes
Participant information sheet	version V4	20/07/2017	10/08/2017	No	Yes
Protocol file	version V3	19/07/2017	10/08/2017	No	No
HRA research summary			28/06/2023	No	No
Protocol file	version 13.0	01/03/2021	27/07/2023	No	No
Other files	version 13.0	01/03/2021	28/07/2023	No	No
Participant information sheet	version 13.0	01/03/2021	28/07/2023	No	Yes
Results article		10/07/2024	04/07/2024	Yes	No

Additional files

ISRCTN79478762_PIS_20July17_Screening_V4.pdf: Uploaded 10/08/2017
ISRCTN79478762_PIS_20July17_Enrolment_V4.pdf: Uploaded 10/08/2017
ISRCTN79478762_PROTOCOL_V3_19July17.pdf: Uploaded 10/08/2017
ISRCTN79478762_PROTOCOL_V13.0_01Mar21.pdf
ISRCTN79478762_PIS_V13.0_01Mar21.pdf
ISRCTN79478762_ConsentForm_V13.0_01Mar21.pdf

Editorial Notes

04/07/2024: Publication reference added.
11/10/2023: Contact details updated.
02/08/2023: The intention to publish date was changed from 31/10/2021 to 31/12/2024.
28/07/2023: The participant information sheet and consent form were uploaded.
27/07/2023: The following changes were made to the study record:
1. The recruitment end date was changed from 30/04/2023 to 27/04/2023.
2. Total final enrolment, IRAS number and protocol added.
3. The inclusion and exclusion criteria were updated.
01/04/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/01/2022 to 30/04/2023.
2. The overall trial end date was changed from 31/08/2022 to 31/10/2023.
3. Recruitment is suspended until 01/06/2022.
16/07/2020: The overall trial end date was changed from 01/08/2022 to 31/08/2022.
13/07/2020: The trial contact details have been made publicly visible.
06/07/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/06/2020 to 31/01/2022.
2. The overall trial end date was changed from 21/10/2020 to 01/08/2022.
06/04/2020: Due to current public health guidance, recruitment for this study has been paused from 19/03/2020. The recruitment end date has been changed from 31/03/2020 to 30/06/2020 to reflect an extension granted in June 2019.
03/04/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Psychosocial Oncology and Survivorship; UKCRC code/ Disease: Cancer/ Malignant neoplasms of ill-defined, secondary and unspecified sites" to "Psychosocial Oncology and Survivorship" following a request from the NIHR.
05/03/2019: Cancer Research UK lay summary link added to plain English summary field.
07/06/2018: internal review
14/05/2018: Internal review.
16/01/2018: Internal review.
11/08/2017: Uploaded protocol Version 3 19 July 2017 (not peer reviewed)