Ignite Creation Date:
2024-05-06 @ 12:18 PM
Last Modification Date:
2024-10-26 @ 12:57 PM
Study NCT ID:
NCT03723291
Status:
UNKNOWN
Last Update Posted:
2021-10-08
First Post:
2018-10-24
Brief Title:
PentoxIfylline and Tocopherol for the Treatment of Post-radiotherapy Fibrosis in Head and Neck Cancer Patients
Sponsor:
University College London
Organization:
University College London
Study Overview
Official Title:
PentoxIfylline and Tocopherol for the Treatment of Post-radiotherapy Fibrosis in Head and Neck Cancer Patients a Feasibility Study
Status:
UNKNOWN
Status Verified Date:
2021-10
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PITSTOP
Brief 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 ratedrop 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
Safetytoxicity 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 800mgday 500IU tocopherol acetate solution twice a day total 1000 IUday 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 inclusionexclusion 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 andor dysphagia
Exclusion Criteria
History of primary cancer resection andor reconstructive surgery to anatomical areas involved in swallowing andor chewing
Concomitant presence of other disorders that may cause pharyngealoral fibrosis
Known hypersensitivity to pentoxifylline or tocopherol vitamin E
History of acute porphyrias or haemorrhagic disorders
Activeongoing hypotension
Diabetes
Pregnancy
Subjects with osteoradionecrosis
Breastfeeding mothers
Subjects with a MIO 12mm
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
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 ratedrop 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
Safetytoxicity 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 800mgday 500IU tocopherol acetate solution twice a day total 1000 IUday 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 inclusionexclusion 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 andor dysphagia
Exclusion Criteria
History of primary cancer resection andor reconstructive surgery to anatomical areas involved in swallowing andor chewing
Concomitant presence of other disorders that may cause pharyngealoral fibrosis
Known hypersensitivity to pentoxifylline or tocopherol vitamin E
History of acute porphyrias or haemorrhagic disorders
Activeongoing hypotension
Diabetes
Pregnancy
Subjects with osteoradionecrosis
Breastfeeding mothers
Subjects with a MIO 12mm
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
Detailed Description:
Fibrosis is a common and irreversible adverse effect of radiotherapy Radiotherapy is used with curative intent in most individuals 70 with head and neck cancer HNC often in combination with surgery andor chemotherapy It is estimated that up to 60 of these individuals will experience persistent fibrosis as a toxic effect of the radiotherapy including trismus and dysphagia As 680000 new HNC casesyear are diagnosed worldwide it is estimated that approximately 270000 individuals will develop persistent trismus andor dysphagia with consequent reduced quality of life QoL due to impaired talking eating chewing and swallowing Malnutrition psychological and social issues add further suffering to affected individuals Mortality is also significantly increased due to aspiration pneumonia In the UK there are 10000 new HN cancer casesyear which translates into approximately 4200 individuals experiencing radiotherapy-induced fibrosis RIF every year Increasing incidence rates of HN cancer suggest that these figures will increase over the next few years This group of cancer survivors represent a challenge for the NHS they have a chronic condition reducing their quality of life and no realistic therapeutic option as no intervention has proven long-term effective Current best NHS practice consists of rehabilitation therapy exercises Although available literature suggests potential efficacy evidence is very weak relevant benefits seem to be short-lived the effect size is usually small and compliance with treatment is often poor As preparatory work for this proposal we have performed a systematic review of the literature which shows that five prospective studies investigated rehabilitation exercises pentoxifylline and botulinum A in the therapy of post-RT trismus Four prospective studies investigated rehabilitation exercises and electrical stimulation in the therapy of post-RT dysphagia
Overall studies were at high risk of bias and there was very limited evidence supporting the efficacy of the above interventions in the post-RT setting
There remains little ongoing clinical research in this field at the present moment clinical trials databases searched in March 2018 Most ongoing recruiting studies focus on preventive strategies during HNC radiotherapy In terms of trials aimed at reducing established post-RT fibrosis we could only find one recruiting Canadian study on manual therapy and one American study on self-care program with no UK study
RIF has been traditionally considered an irreversible disorder characterised by the generation of reactive oxygen species vascular damage pro-fibrotic inflammation promotion of collagen formation and the development of excessive fibrous tissue However research during the last 15 years has shown that co-administration of pentoxifylline and tocopherol vitamin E can reduce and reverse the fibrotic process Pentoxifylline is known to improve microcirculation inhibit fibroblast proliferation reduce extracellular matrix production and increase collagenase activity Tocopherol Vitamin E has antioxidant properties The precise mechanisms by which the pentoxifyllinetocopherol vitamin E combination interacts with fibro-atrophic tissues and induces fibrotic process reversibility are still unclear It has been suggested that the anti-fibrotic effects are consequence of the inhibition of fibroblast proliferation and extracellular matrix production increased collagenase activity as well as a reduction in reactive oxygen species Clinical trials have indicated that the combination of pentoxifylline and tocopherol vitamin E can decrease and even reverse RIF in individuals irradiated to the breast pelvis lung and prostate leading to functional and aesthetic benefits It is not known whether this therapy may have similar beneficial effects in HNC survivors with permanent RIF trismus andor dysphagia Preliminary small-scale studies suggest that this may be the case and support the notion that pentoxifylline and tocopherol vitamin E represent a promising treatment that is worth investigating in well-designed clinical trials The best available evidence comes from a 2001 uncontrolled small 16 subjects pilot study that showed functional improvement in subjects with established post-radiotherapy trismus after an 8-week course of pentoxifylline as monotherapy Other studies have reported the beneficial effects of pentoxyfilline monotherapy or in combination with tocopherol vitamin E in reducing andor preventing RIF in HNC but these focused on cutaneoussubcutaneous neck fibrosis and did not measure trismusdysphagia There is a clear need for better-designed clinical research as more robust evidence is required in order to influence changes in NHS practice and improve the quality of life of HNC survivors
The main study will be a multicentre randomised controlled trial with two arms including the experimental intervention plus the current best standard treatment versus the current best treatment as comparator 11 The main outcome will be anticipated to be patient-centred and measured via a validated instrument QoL questionnaire with secondary outcomes including other patient-centred measures validated functional questionnaires as well as clinician-rated and instrumental outcomes However several aspects of the main trial remain unknownunclear and would require clarification via a feasibility study
PITSTOP is a feasibility 36-month randomised trial of the best standard therapy alone rehabilitation exercises vs treatment with pentoxifylline and tocopherol vitamin E in addition to best standard therapy rehabilitation exercises in 50 participants with radiotherapy-induced fibrosis of the head and neck It is a two-centre study with a 11 randomisation into two study arms At each site a blocked randomisation list will be used to ensure an approximate balance in numbers between the two groups Allocation concealment will be ensured using an online randomisation service Sealed Envelope
Overall studies were at high risk of bias and there was very limited evidence supporting the efficacy of the above interventions in the post-RT setting
There remains little ongoing clinical research in this field at the present moment clinical trials databases searched in March 2018 Most ongoing recruiting studies focus on preventive strategies during HNC radiotherapy In terms of trials aimed at reducing established post-RT fibrosis we could only find one recruiting Canadian study on manual therapy and one American study on self-care program with no UK study
RIF has been traditionally considered an irreversible disorder characterised by the generation of reactive oxygen species vascular damage pro-fibrotic inflammation promotion of collagen formation and the development of excessive fibrous tissue However research during the last 15 years has shown that co-administration of pentoxifylline and tocopherol vitamin E can reduce and reverse the fibrotic process Pentoxifylline is known to improve microcirculation inhibit fibroblast proliferation reduce extracellular matrix production and increase collagenase activity Tocopherol Vitamin E has antioxidant properties The precise mechanisms by which the pentoxifyllinetocopherol vitamin E combination interacts with fibro-atrophic tissues and induces fibrotic process reversibility are still unclear It has been suggested that the anti-fibrotic effects are consequence of the inhibition of fibroblast proliferation and extracellular matrix production increased collagenase activity as well as a reduction in reactive oxygen species Clinical trials have indicated that the combination of pentoxifylline and tocopherol vitamin E can decrease and even reverse RIF in individuals irradiated to the breast pelvis lung and prostate leading to functional and aesthetic benefits It is not known whether this therapy may have similar beneficial effects in HNC survivors with permanent RIF trismus andor dysphagia Preliminary small-scale studies suggest that this may be the case and support the notion that pentoxifylline and tocopherol vitamin E represent a promising treatment that is worth investigating in well-designed clinical trials The best available evidence comes from a 2001 uncontrolled small 16 subjects pilot study that showed functional improvement in subjects with established post-radiotherapy trismus after an 8-week course of pentoxifylline as monotherapy Other studies have reported the beneficial effects of pentoxyfilline monotherapy or in combination with tocopherol vitamin E in reducing andor preventing RIF in HNC but these focused on cutaneoussubcutaneous neck fibrosis and did not measure trismusdysphagia There is a clear need for better-designed clinical research as more robust evidence is required in order to influence changes in NHS practice and improve the quality of life of HNC survivors
The main study will be a multicentre randomised controlled trial with two arms including the experimental intervention plus the current best standard treatment versus the current best treatment as comparator 11 The main outcome will be anticipated to be patient-centred and measured via a validated instrument QoL questionnaire with secondary outcomes including other patient-centred measures validated functional questionnaires as well as clinician-rated and instrumental outcomes However several aspects of the main trial remain unknownunclear and would require clarification via a feasibility study
PITSTOP is a feasibility 36-month randomised trial of the best standard therapy alone rehabilitation exercises vs treatment with pentoxifylline and tocopherol vitamin E in addition to best standard therapy rehabilitation exercises in 50 participants with radiotherapy-induced fibrosis of the head and neck It is a two-centre study with a 11 randomisation into two study arms At each site a blocked randomisation list will be used to ensure an approximate balance in numbers between the two groups Allocation concealment will be ensured using an online randomisation service Sealed Envelope
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None