A clinic feasibility study to assess whether the use of two combined medicines (pentoxifylline and tocopherol) can prevent radiotherapy-related changes of the mouth and face compared to the current standard of care in the head and neck cancer population

ISRCTN	ISRCTN74484952
DOI	https://doi.org/10.1186/ISRCTN74484952
EudraCT/CTIS number	2018-001153-27
IRAS number	223295
Secondary identifying numbers	1.0; CPMS: 40028

Submission date: 02/08/2019
Registration date: 27/08/2019
Last edited: 13/12/2024

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

See https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-treatment-prevent-radiation-fibrosis-radiotherapy-head-neck-cancer-can-cause-penve (added 15/01/2021)

Contact information

Dr Vinod Patel
Public

Department of Oral Surgery
Floor 22
Guy’s Tower Wing
Guy’s Dental Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom

Phone	+44 (0)2071883885
Email	vinod.patel@gstt.nhs.uk

Dr Gabriella Wojewodka
Scientific

OCRU Research Portfolio Manager
Oral Clinical Research Unit
Floor 25
Guy’s Tower Wing
Guy’s Dental Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom

Phone	+44 (0)207 188 7188 Ext 51980
Email	gabriella.wojewodka@kcl.ac.uk

Study information

Study design	Open-label two-arm randomised control trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Prevention
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet.
Scientific title	A prospective randomised controlled trial comparing the use of open-label pentoxifylline and tocopherol versus current standard of care for the prevention of fibrosis-related outcomes in irradiated head and neck oncology patients (feasibility study)
Study acronym	PenVe
Study hypothesis	The use of pentoxifylline and tocopherol reduce radiation-induced fibrosis events such as osteoradionecrosis, trismus and dysphagia.
Ethics approval(s)	Approved 22/02/2019, London - Harrow Research Ethics Committee (Level 3, Block B Whitefriars Lewins Mead, Bristol, BS1 2NT, UK; Tel: +44 (0)20 7104 8057; Email: nrescommittee.london-harrow@nhs.net), ref: 18/LO/1910
Condition	Osteoradionecrosis (ORN) of the jaws, trismus and dysphagia following radiotherapy in patients with head and neck cancer
Intervention	Participants requiring head and neck radiotherapy as part of their standard treatment for cancer are randomised to one of two groups. Participants will be randomised in a 3:1 ratio (intervention: standard care) to enable better assessment of outcomes in the intervention group, including patient preference for drug formulation and the side effect profile. Randomisation will use permuted blocks of varying sizes and will be undertaken via a bespoke online randomization service provided by King’s Clinical Trials Unit (KCTU). This is an open-label study. Neither patients, researchers nor statisticians will be blinded. Both groups will continue to receive best standard of care in current practice, but group B will additionally receive pentoxifylline 400 mg BD and tocopherol 1000IU OD after their radiotherapy. Group B will also receive additional follow up calls. All participants will be in the trial for 6 months and have 4 study visits. Maximum duration of treatment of a participant: 6 months.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Pentoxifylline, tocopherol
Primary outcome measure	Feasibility of the trial: 1. Patient’s preference of drug formulation and subsequent side effects, assessed through: 1.1. Patient contact by daily telephone call in the first 2 weeks, 3 weekly telephone calls (+/- 1 week) in conjunction with patient diary, 3 monthly clinical follow up, 6 monthly clinical follow-up. This will be recorded in the patient notes and transcribed to the eCRF 1.2. Independent and reflective patient feedback at focus groups 2. Recruitment and retention to the trial, and patient adherence to the drugs, assessed through: 2.1. Screening and enrolment log which is overseen by the PI and research nurse. The numbers consented and randomised will be recorded in the eCRF 2.2. Patient contact at 6 monthly clinical follow-up. This will be recorded in the patient notes and transcribed to the eCRF 2.3. Daily telephone call in the first 2 weeks, 3 weekly telephone calls (+/- 1 week) in conjunction with patient diary, 3 monthly clinical follow up, 6 monthly clinical follow-up. This will be recorded in the patient notes and transcribed to the eCRF 2.4. Independent and reflective patient feedback at focus groups 2.5. Vitamin E blood test taken at baseline, 3 months and 6 months 2.6. Patients asked to bring any remaining pentoxifylline and vitamin E for measurement of liquid or tablets left at formulation changeover and at month 6 3. Appropriateness and acceptability of the outcome measurement tools, assessed through completed questionnaires at trial visits and through focus groups
Secondary outcome measures	1. Presence of osteoradionecrosis assessed by clinical review including an oral examination at month 3 and month 6 2. Mouth opening measured using ruler at baseline, month 3 and month 6 3. Swallowing capacity assessed using Sydney swallow questionnaire at baseline, month 3 and month 6 4. Quality of life assessed using Washington quality of life questionnaire at baseline, month 3 and month 6
Overall study start date	22/04/2019
Overall study end date	30/09/2023

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	68
Total final enrolment	54
Participant inclusion criteria	1. Patients (≥18 years) presenting with a primary head and neck (H&N) tumour requiring radiotherapy treatment and placing them in the highest risk group for developing osteoradionecrosis, trismus and dysphagia. These include: 1.1. Oropharynx (tonsil, base of tongue) 1.2. Nasopharynx 1.3. Floor of mouth 1.4. Lateral aspect of the tongue 2. Oncology treatment aiming for the intent to cure 3. Patients able to consent and willing to participate
Participant exclusion criteria	1. Previous history of H&N cancer 2. Patients treated with any drug implicated to cause medication-related osteonecrosis of the jaw (MRONJ). These include bisphosphonates, denosumab, radium 223, tyrosine kinase inhibitors and bevacizumab 3. Any patient with significant medical history where taking part in this study may potentially compromise their health. 4. Women who are pregnant or breastfeeding or of childbearing age not on adequate contraception 5. Patients lacking capacity to consent 6. Oncology treatment for palliative care 7. Patients deemed to have a high risk of recurrent tumour 8. Patients with a previous history of cerebral haemorrhage, extensive retinal haemorrhage, acute myocardial infarction, severe cardiac arrhythmias and impaired renal function, impaired liver function which in the expert opinion of the principal 9. investigator present a risk to the patient 10. Known drug allergy or sensitivity to pentoxifylline (or methylxanthines) and alpha-tocopheryl or any constituents of the medication (e.g. methyl and propyl hydroxybenzoates or rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency) 11. Patients taking theophylline or oestrogens 12. Patients with metastatic disease 13. Patient participating in other drug (CTIMP) trials
Recruitment start date	29/07/2019
Recruitment end date	13/07/2022

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Guy's & St Thomas's NHS Foundation Trust

Fl 23, Oral Surgery Dept, Guy's Dental Hospital
London
SE1 9RT
United Kingdom

Sponsor information

Guys & St Thomas NHS Foundation Trust
Hospital/treatment centre

King’s Health Partners Clinical Trials Office
F16 Tower Wing Guys Hospital
Great Maze Pond
London
SE1 9RT
England
United Kingdom

Phone	+44 (0)20 7188 5732
Email	helen.critchley@kcl.ac.uk
"ROR"	https://ror.org/00j161312

Funders

Funder type

Government

Research for Patient Benefit Programme
Government organisation / National government

Alternative name(s): NIHR Research for Patient Benefit Programme, RfPB
Location: United Kingdom

Results and Publications

Intention to publish date	01/06/2024
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	Scientific journal and international conferences
IPD sharing plan	The data sharing plans for the current study are unknown and will be made available at a later date

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No

Editorial Notes

13/12/2024: IRAS number added.
11/10/2022: The following changes have been made:
1. The recruitment end date has been changed from 30/06/2022 to 13/07/2022.
2. The overall trial end date has been changed from 01/10/2022 to 30/09/2023.
3. The intention to publish date has been changed from 01/06/2022 to 01/06/2024.
4. The total final enrolment has been added.
06/10/2021: The scientific contact was updated.
14/04/2021: The recruitment end date was changed from 29/01/2021 to 30/06/2022.
14/04/2021: The following changes were made to the trial record:
1. The overall trial end date was changed from 29/04/2021 to 01/10/2022.
2. The intention to publish date was changed from 01/06/2021 to 01/06/2022.
15/01/2021: Cancer Research UK plain English summary link added.
13/03/2020: Internal review.
08/11/2019: Internal review.
19/08/2019: Trial's existence confirmed by the NIHR.