PentoxIfylline and Tocopherol for the Treatment of Post-radiotherapy Fibrosis in Head and Neck Cancer Patients

Summary

Objectives:

This is a feasibility study in preparation for the main multicentre randomised trial, which is anticipated to have two arms:

* Arm A: the current best standard of care \[rehabilitation exercises\]
* Arm B: the current best standard of care \[rehabilitation exercises\] + the experimental intervention

In this feasibility trial the following aspects will be evaluated:

* Recruitment rates \[that is also willingness to be randomised\]
* Feasibility of providing the experimental intervention at the NHS study sites
* Retention rate/drop out rate
* Feasibility and acceptability of (i) proposed primary outcome \[patient-centred\], (ii) a range of additional patient-centred and clinician-centred outcomes
* Standard deviation of the proposed primary outcome so to inform sample size calculation of the main trial.
* Safety/toxicity of the study medication.

Type of trial: Multicentre, parallel group, randomised controlled trial in 50 patients with radiotherapy-induced fibrosis of the head and neck.

Trial design and methods:

Participants over the age of 18, with radiotherapy-induced fibrosis of the head and neck will be given information about the trial and invited to participate.

50 participants who consent will be recruited and randomised to either:

* Treatment with pentoxifylline 400 mg tablets twice a day \[total 800mg/day\] + 500IU tocopherol acetate solution twice a day \[total 1000 IU/day\] in addition to best standard care \[a structured programme of rehabilitation exercises\] for 6 months or
* Best standard of care \[a structured programme of rehabilitation exercises\] for 6 months.

Randomisation will be carried out online

Trial duration per subject: 6 months Estimated total trial duration: 56 months Planned trial sites: Multi-site Total number of subjects planned: 50 participants

Main inclusion/exclusion criteria:

Inclusion Criteria:

* Subjects aged ≥18 years
* Previous history of Head \& Neck Cancer
* Previous radiotherapy to the Head \& Neck - minimum 50 Gy completed at least 12 months before screening visit
* Cancer-free for a minimum of 12 months after completion of radiotherapy.
* Diagnosis of radiotherapy-induced fibrosis of the head and neck: trismus and/or dysphagia
* Diagnosis of RIF of the head and neck by patient defined criteria:
* Trismus: "Does your mouth opening feel restricted?" Dysphagia: a score of 3 or more on the 10-item Eating Assessment Tool (EAT-10)29
* No history of primary cancer resection and/or reconstructive surgery to anatomical areas involved in swallowing and/or chewing with potential for altered and reconstructed muscular anatomy that may not be amenable to exercise/respond to antifibrotic medications (with the exception of diagnostic biopsy/tonsillectomy and neck dissections)
* Able to take study medications orally
* Subjects of child-bearing potential/potency must adhere to one method of highly effective contraception

Exclusion Criteria:

* History of primary cancer resection and/or reconstructive surgery to anatomical areas involved in swallowing and/or chewing.
* Concomitant presence of other disorders that may cause pharyngeal/oral fibrosis
* Known hypersensitivity to pentoxifylline or tocopherol (vitamin E).
* History of acute porphyrias or haemorrhagic disorders
* Active/ongoing hypotension
* Diabetes
* Pregnancy
* Subjects with osteoradionecrosis
* Breastfeeding mothers
* Subjects with a MIO \<12mm
* Recurrent H\&N cancer or second primary H\&N cancer
* History of cerebral haemorrhage, extensive retinal haemorrhage or is at risk of increased bleeding (including those taking anticoagulants and platelet aggregation inhibitors)
* History of acute myocardial infarction, severe coronary artery disease, severe cardiac arrhythmias
* History of hepatic or renal impairment
* Expected non-compliance with treatment interventions or is considered unsuitable for trial participation at the discretion of the treating clinician
* Rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency

Statistical methodology and analysis: Analysis of this feasibility trial will be mainly descriptive, measuring recruitment rate, acceptance of randomisation, attrition from treatment and trial, and completion rates for the outcome measures (to gauge acceptability and appropriateness).

Conditions

• Head and Neck Fibrosis

Interventions

COMBINATION_PRODUCT

Arm B: A combination of pentoxifylline and tocopherol acetate in addition to best standard care [a structured programme of rehabilitation exercises] for 6 months

• Arm B: A combination of pentoxifylline 800 mg/d in two 400-mg tablets and 1,000 IU/d of tocopherol acetate in two 500-IU aliquots in addition to best standard care \[a structured programme of rehabilitation exercises\] for 6 months

PROCEDURE

• Arm A: Best standard of care only [a structured programme of rehabilitation exercises] for 6 months

Prophylactic swallowing exercises consist of strap muscle exercises, airway protection exercises and base of tongue exercises

Sponsors & Collaborators

• National Institute for Health Research, United Kingdom

  collaborator OTHER_GOV

• University College, London

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-09-01

Primary Completion

2021-12-31

Completion

2022-06-30

Countries

• United Kingdom

Study Locations