Ignite Creation Date:
2024-06-16 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06421649
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-24
First Post:
2024-04-25
Brief Title:
Investigating the Role of Adjuvant Proton Beam Therapy in Patients With Parotid Carcinoma
Sponsor:
The Christie NHS Foundation Trust
Organization:
The Christie NHS Foundation Trust
Study Overview
Official Title:
An Evaluative Commissioning Study to Investigate the Role of Adjuvant Proton Beam Radiotherapy in Patients With Localised Parotid Carcinoma
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
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:
PRONTO
Brief Summary:
Proton Beam Therapy PBT is an advanced radiotherapy technique There are two National Health Service NHS PBT treatment centres in the UK one in Manchester and one in London The NHS is committed to ensuring the best use of this limited resource by investigating which patients will benefit from PBT treatment
Evaluative Commissioning in Protons ECIP is a programme of studies that explore the role of PBT for patients with different types of cancer They are funded by NHS England ECIP studies are not randomised studies which means that all eligible patients will be offered proton therapy Any patient in the United Kingdom UK can be referred and for patients that need to travel far to their nearest centre accommodation will be available
The main benefit of PBT compared with photon radiotherapy is the predicted reduction in radiation dose to surrounding healthy tissues With photon radiotherapy some radiation passes beyond the target area affecting healthy tissues and causing side-effects With PBT the radiation dose stops within the target area causing less damage to surrounding tissues and limiting side effects
PRONTO is a study within the ECIP programme exploring whether PBT can reduce treatment side effects for patients with salivary gland cancers who need radiotherapy following surgery Whilst radiotherapy is associated with good cancer control it commonly causes problematic side-effects such as loss of taste and dry mouth These can be permanent and can negatively affect someones quality of life PRONTOs main aim is to see if PBT can reduce the loss of taste following radiotherapy
Participants in PRONTO will be closely monitored by the medical team and with questionnaires The patient experience will be compared to what we would expect with standard photon radiotherapy
Evaluative Commissioning in Protons ECIP is a programme of studies that explore the role of PBT for patients with different types of cancer They are funded by NHS England ECIP studies are not randomised studies which means that all eligible patients will be offered proton therapy Any patient in the United Kingdom UK can be referred and for patients that need to travel far to their nearest centre accommodation will be available
The main benefit of PBT compared with photon radiotherapy is the predicted reduction in radiation dose to surrounding healthy tissues With photon radiotherapy some radiation passes beyond the target area affecting healthy tissues and causing side-effects With PBT the radiation dose stops within the target area causing less damage to surrounding tissues and limiting side effects
PRONTO is a study within the ECIP programme exploring whether PBT can reduce treatment side effects for patients with salivary gland cancers who need radiotherapy following surgery Whilst radiotherapy is associated with good cancer control it commonly causes problematic side-effects such as loss of taste and dry mouth These can be permanent and can negatively affect someones quality of life PRONTOs main aim is to see if PBT can reduce the loss of taste following radiotherapy
Participants in PRONTO will be closely monitored by the medical team and with questionnaires The patient experience will be compared to what we would expect with standard photon radiotherapy
Detailed Description:
Malignant parotid tumours are uncommon Whilst 85 of salivary gland tumours originate in the parotid gland only 20-25 of these are malignant representing only 3-6 of head and neck cancers This is about 650 patientsyear in the UK
Standard treatment for local disease is with surgical resection followed by adjuvant radiotherapy for patients with high-risk features Local control and 5-year survival rates are good at 70 and 80 respectively but radiotherapy is associated with considerable toxicity More than 70 of patients receiving photon therapy experience significant dysgeusia taste lossalteration This can be permanent is associated with weight loss diminished appetite dry mouth and negatively impact on Quality of Life QoL
The putative benefit of proton beam radiotherapy PBT relates to its characteristic deposition in the body which limits the radiation dose received by surrounding healthy tissues We hypothesise that irradiating the post-operative parotid bed with PBT rather than Intensity Modulated Radiation Therapy IMRT will reduce the dose delivered to the Organs at Risk OAR in particular the oral cavity OC leading to a reduction in acute and long term taste lossalteration The advantageous physical properties of PBT may also improve other side effects including fatigue mucositis nausea vomiting and potentially hearing problems as well as overall QoL
Radiotherapy planning studies
Radiation planning studies have repeatedly shown statistically significant reductions in the dose delivered to healthy tissues including the oral cavity brainstem spinal cord contralateral parotid ipsilateral and contralateral submandibular glands and ipsilateral temporal lobe In particular radiotherapy doses to the oral cavity are significantly reduced typically to below 10 Gray Gy No routinely contoured OAR or region of interest was consistently found to have higher doses planning with protons although skin dose may be higher
Clinical Trials
Whilst there are no randomised control trials comparing protons and photons for this cohort However there is some clinical evidence that the use of PBT leads to clinically meaningful improvements in the side effects experienced by patients One study compared acute toxicities between matched groups receiving either protons or photons demonstrating statistically significant reductions in dysgeusia fatigue mucositis and nausea and vomiting in patients undergoing proton treatment In other studies PBT is associated with very low toxicity level such as less than 30 of patients experiencing any dysgeusia This compares favourably to photon experience such as in the phase 3 randomised controlled trial A Multicentre Randomised Study of Cochlear Sparing Intensity Modulated Radiotherapy Versus Conventional Radiotherapy in Patients with Parotid Tumours COSTAR where approximately 60 of patients reported dysgeusia in the Head Neck 35 HN35 questionnaire at 1 year The PRONTO study is powered to identify a clinically meaningful reduction in taste dysfunction of at least 20
Whilst late toxicities are also likely under-reported in the retrospective international data the published literature to date is very reassuring The mean dose to the ipsilateral temporal lobe is reportedly reduced and reflected in low levels of subsequent headache fatigue andor memory change Similarly whilst poorly captured low levels of hearing dysfunction or otalgia have also been reported following PBT
There is no rationale at all that cancer outcomes either local control or overall survival will be worse with PBT than photon treatment In studies to date local control approximately 95 and overall survival 89-96 has been excellent and comparative to known photon experience
Standard treatment for local disease is with surgical resection followed by adjuvant radiotherapy for patients with high-risk features Local control and 5-year survival rates are good at 70 and 80 respectively but radiotherapy is associated with considerable toxicity More than 70 of patients receiving photon therapy experience significant dysgeusia taste lossalteration This can be permanent is associated with weight loss diminished appetite dry mouth and negatively impact on Quality of Life QoL
The putative benefit of proton beam radiotherapy PBT relates to its characteristic deposition in the body which limits the radiation dose received by surrounding healthy tissues We hypothesise that irradiating the post-operative parotid bed with PBT rather than Intensity Modulated Radiation Therapy IMRT will reduce the dose delivered to the Organs at Risk OAR in particular the oral cavity OC leading to a reduction in acute and long term taste lossalteration The advantageous physical properties of PBT may also improve other side effects including fatigue mucositis nausea vomiting and potentially hearing problems as well as overall QoL
Radiotherapy planning studies
Radiation planning studies have repeatedly shown statistically significant reductions in the dose delivered to healthy tissues including the oral cavity brainstem spinal cord contralateral parotid ipsilateral and contralateral submandibular glands and ipsilateral temporal lobe In particular radiotherapy doses to the oral cavity are significantly reduced typically to below 10 Gray Gy No routinely contoured OAR or region of interest was consistently found to have higher doses planning with protons although skin dose may be higher
Clinical Trials
Whilst there are no randomised control trials comparing protons and photons for this cohort However there is some clinical evidence that the use of PBT leads to clinically meaningful improvements in the side effects experienced by patients One study compared acute toxicities between matched groups receiving either protons or photons demonstrating statistically significant reductions in dysgeusia fatigue mucositis and nausea and vomiting in patients undergoing proton treatment In other studies PBT is associated with very low toxicity level such as less than 30 of patients experiencing any dysgeusia This compares favourably to photon experience such as in the phase 3 randomised controlled trial A Multicentre Randomised Study of Cochlear Sparing Intensity Modulated Radiotherapy Versus Conventional Radiotherapy in Patients with Parotid Tumours COSTAR where approximately 60 of patients reported dysgeusia in the Head Neck 35 HN35 questionnaire at 1 year The PRONTO study is powered to identify a clinically meaningful reduction in taste dysfunction of at least 20
Whilst late toxicities are also likely under-reported in the retrospective international data the published literature to date is very reassuring The mean dose to the ipsilateral temporal lobe is reportedly reduced and reflected in low levels of subsequent headache fatigue andor memory change Similarly whilst poorly captured low levels of hearing dysfunction or otalgia have also been reported following PBT
There is no rationale at all that cancer outcomes either local control or overall survival will be worse with PBT than photon treatment In studies to date local control approximately 95 and overall survival 89-96 has been excellent and comparative to known photon experience
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