Condition category
Cancer
Date applied
02/08/2019
Date assigned
27/08/2019
Last edited
27/08/2019
Prospective/Retrospective
Retrospectively 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 Vinod Patel

ORCID ID

Contact details

Department of Oral Surgery
Floor 22
Guy’s Tower Wing
Guy’s Dental Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
+44 (0)2071883885
vinod.patel@gstt.nhs.uk

Type

Scientific

Additional contact

Ms Nicola Garrett

ORCID ID

Contact details

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
+44 (0)207 188 7188 Ext 51980
nicola.garrett@kcl.ac.uk

Additional identifiers

EudraCT number

2018-001153-27

ClinicalTrials.gov number

Nil known

Protocol/serial number

1.0; CPMS: 40028

Study information

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)

Acronym

PenVe

Study hypothesis

The use of pentoxifylline and tocopherol reduce radiation-induced fibrosis events such as osteoradionecrosis, trismus and dysphagia.

Ethics approval

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

Study design

Open-label two-arm randomised control trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Condition

Osteoradionecrosis (ORN) of the jaws, trismus, dysphagia

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

Phase

Phase II

Drug names

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 trial start date

22/04/2019

Overall trial end date

29/04/2021

Reason abandoned (if study stopped)

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

68

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

29/01/2021

Locations

Countries of recruitment

United Kingdom

Trial 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

Organisation

Guys & St Thomas NHS Foundation Trust

Sponsor details

King’s Health Partners Clinical Trials Office
F16 Tower Wing Guys Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
+44 (0)20 7188 5732
helen.critchley@kcl.ac.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Research for Patient Benefit Programme

Alternative name(s)

NIHR Research for Patient Benefit Programme, RfPB

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Scientific journal and international conferences

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

01/06/2021

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

19/08/2019: Trial's existence confirmed by the NIHR.