Can proton beam therapy improve survival and reduce late side effects compared with standard-of-care intensity-modulated radiotherapy in patients with sinonasal cancer?

PROton beam Therapy versus Intensity-modulated radiotherapy for Sinonasal cancer

Status

Recruiting

Phases

Unknown

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN15983654

Enrollment

276

Registered

2024-03-26

Start date

2024-09-16

Completion date

Unknown

Last updated

2026-03-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-metastatic sinonasal cancer Cancer

Interventions

PROTIS is an open-label phase III multi-centre prospective randomised controlled trial. The overall aim is to assess whether proton beam therapy (PBT) compared with standard-of-care intensity-modulate

Eligibility

Sex/Gender

All

Age

25 Years to 110 Years

Inclusion criteria

Inclusion criteria: Current inclusion criteria as of 31/10/2024: 1. Written and informed consent obtained from participants 2. Agreement of participant to comply with the requirements of the trial, including travel and residential stay at the proton centre if allocated to PBT 3. Histologically confirmed: 3.1. Sinonasal squamous cell carcinoma (SNSCC) or 3.2. Sinonasal adenocarcinoma (SNAC) 4. Primary tumour (T) staging (AJCC 8th edition): 4.1. T3-4 all subsites (maxillary, ethmoid, sphenoid or frontal sinuses, and/or nasal cavity) or 4.2. T2 nasal cavity involving ethmoid sinus 5. Age >=25 years old 6. WHO performance status 0-1 7. Multidisciplinary team (MDT) decision for curative intent treatment 7.1. with surgery or 7.2. without _____ Previous inclusion criteria: 1. Written and informed consent obtained from participants 2. Agreement of participant to comply with the requirements of the trial, including travel and residential stay at the proton centre if allocated to PBT 3. Histologically confirmed: 3.1. Sinonasal squamous cell carcinoma (SNSCC) or 3.2. Sinonasal adenocarcinoma (SNAC) 4. Primary tumour (T) staging (AJCC 8th edition): 4.1. T3-4 all subsites (maxillary, ethmoid, sphenoid or frontal sinuses, and/or nasal cavity) or 4.2. T2 nasal cavity involving ethmoid sinus 5. Age > = 16 years old 6. WHO performance status 0-1 7. Multidisciplinary team (MDT) decision for curative intent treatment 7.1. with surgery or 7.2. without

Exclusion criteria

Exclusion criteria: 1. Distant metastatic disease, as determined by routine pre-operative radiological staging investigations 2. Previous head and neck radiotherapy 3. Any invasive malignancy within the previous 2 years (other than non-melanomatous skin carcinoma or cervical carcinoma in situ) 4. Previous or concurrent illness that would interfere with completion of therapy, trial assessments or follow-up (in the opinion of PI) 5. Pregnant or breastfeeding women 6. Participants unwilling or unable to use adequate non-hormonal contraception

Design outcomes

Primary

Measure	Time frame
Disease-free survival (DFS) measured using a biopsy; a biopsy with pathological confirmation will define a DFS event. Where a biopsy is not possible, correlative imaging can be used as a surrogate to define a DFS event from randomisation to cancer recurrence, death from any cause, or 5-year follow-up.	—

Secondary

Measure	Time frame
1. Loco-regional tumour control measured using a clinical evaluation post-treatment. Additional non-trial visits will be carried out as per local policy and standard of care, from randomisation to tumour growth or 5 years follow-up. 2. Distant failure measured during follow-up via imaging if prompted by participants having symptoms of concern and as per standard of care from randomisation to distant failure or 5 years follow-up. 3. Overall survival measured using all deaths reported from randomisation to death or 5 years follow-up. 4. Acute severe (grade 3-5) toxicity events measured by physician recorded CTCAE v5.0 up to 12 weeks from completion of treatment. 5. Late severe (grade 3-5) toxicity events measured by physician recorded CTCAE v5.0 from 12 weeks to 5 years from completion of treatment. 6. Neuro-cognitive decline measured using EORTC core tests conducted and scored at sites and compiling the corresponding scoring manuals/algorithms at baseline, 12 weeks, 52 weeks, 2, 3, 4 and 5 years. 7. Visual function measured using visual acuity, visual fields, Lens exam, IOP, fundus exam, media clarity, levator function, pupil function, colour vision, ocular alignment/movement assessment, lid/lash/ocular surface exam and Optical Coherence Tomography (OCT) at baseline, 2 and 5 years. 8. Olfactory function measured using UPSIT at baseline and 2 years. 9. Pituitary function measured using blood tests collected as per standard of care Growth hormone (IGF-1), Adrenal (ACTH/cortisol (9am)), and Thyroid (TSH fT4 fT3), Gonadotrophins/ sex steroids (FSH/LH/SHBG testosterone or oestradiol, prolactin) at baseline, 52 weeks, 2 and 5 years. 10. Auditory function measured using pure tone audiometry +/- extended high frequencies at baseline and 2 years. 11. Trismus measured using maximum interincisal distance at baseline, 12, 52 weeks and 2 years. 12. Brain injury/necrosis measured using central review of MRI scans (collected as standard of care sinus/neck) at baseline, 52 weeks,	—

Measure

Time frame

1. Loco-regional tumour control measured using a clinical evaluation post-treatment. Additional non-trial visits will be carried out as per local policy and standard of care, from randomisation to tumour growth or 5 years follow-up. 2. Distant failure measured during follow-up via imaging if prompted by participants having symptoms of concern and as per standard of care from randomisation to distant failure or 5 years follow-up. 3. Overall survival measured using all deaths reported from randomisation to death or 5 years follow-up. 4. Acute severe (grade 3-5) toxicity events measured by physician recorded CTCAE v5.0 up to 12 weeks from completion of treatment. 5. Late severe (grade 3-5) toxicity events measured by physician recorded CTCAE v5.0 from 12 weeks to 5 years from completion of treatment. 6. Neuro-cognitive decline measured using EORTC core tests conducted and scored at sites and compiling the corresponding scoring manuals/algorithms at baseline, 12 weeks, 52 weeks, 2, 3, 4 and 5 years. 7. Visual function measured using visual acuity, visual fields, Lens exam, IOP, fundus exam, media clarity, levator function, pupil function, colour vision, ocular alignment/movement assessment, lid/lash/ocular surface exam and Optical Coherence Tomography (OCT) at baseline, 2 and 5 years. 8. Olfactory function measured using UPSIT at baseline and 2 years. 9. Pituitary function measured using blood tests collected as per standard of care Growth hormone (IGF-1), Adrenal (ACTH/cortisol (9am)), and Thyroid (TSH fT4 fT3), Gonadotrophins/ sex steroids (FSH/LH/SHBG testosterone or oestradiol, prolactin) at baseline, 52 weeks, 2 and 5 years. 10. Auditory function measured using pure tone audiometry +/- extended high frequencies at baseline and 2 years. 11. Trismus measured using maximum interincisal distance at baseline, 12, 52 weeks and 2 years. 12. Brain injury/necrosis measured using central review of MRI scans (collected as standard of care sinus/neck) at baseline, 52 weeks,

—

Countries

England, United Kingdom, Wales

Contacts

Public ContactPROTIS Study Team

PROTIS@liverpool.ac.uk-

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Mar 14, 2026