Acromegaly Due to Pituitary AdenomaPhase 3PRESTONCT07813351
PRESTO: A Phase III Randomised Controlled Trial of Dose-escalated Proton Beam Therapy Versus Standard of Care Radiotherapy for Functioning Pituitary Tumours
A Phase 3 study testing Standard dose Intensity-Modulated Radiation Therapy (IMRT), Standard dose Proton Beam Therapy (PBT) and Escalated dose Proton Beam Therapy (PBT) in people with Acromegaly Due to Pituitary Adenoma and Cushing's Disease, run by University College, London.
Trial summary
The goal of this clinical trial is to evaluate whether a higher dose of radiotherapy can lead to better outcomes for participants with functioning pituitary tumours. The main question it aims to answer is whether a greater proportion of participants will achieve normal hormone levels with the higher dose of proton… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acromegaly Due to Pituitary Adenoma, Cushing's Disease, Pituitary Adenoma
- What is being tested?
- Standard dose Intensity-Modulated Radiation Therapy (IMRT), Standard dose Proton Beam Therapy (PBT) and Escalated dose Proton Beam Therapy (PBT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- No sites listed yet
- Study dates
- Sep 2026to Sep 2032
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Neuropathological confirmation of growth hormone (acromegaly) or ACTH (Cushing's disease) secreting pituitary adenoma after neurosurgical intervention.
- Ongoing hormonal hypersecretion as defined by local and age-specific normal range values without hormone supressing medication (may need washout).
- Multidisciplinary team meeting recommendation for fractionated radiotherapy.
- Karnofsky performance status ≥70.
- Age ≥18 years.
- Agreement to travel to a proton beam therapy centre (i.e. UCLH or The Christie) as required.
- Written informed consent.
- Agreement to be followed up at a local PRESTO trial site.
Who cannot join
- Women who are pregnant or breast feeding.
- Prior cranial or head and neck radiotherapy treatment, including Stereotactic radiosurgery (SRS).
- Unsuitability or intolerability of MRI scans.
- Severe active comorbidities that limit compliance with trial requirements.
- Prior invasive malignancy unless disease free interval of ≥3 years.
- Unable to travel to the PBT centres as per trial requirements.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
The goal of this clinical trial is to evaluate whether a higher dose of radiotherapy can lead to better outcomes for participants with functioning pituitary tumours. The main question it aims to answer is whether a greater proportion of participants will achieve normal hormone levels with the higher dose of proton beam radiotherapy than with standard radiotherapy treatment doses.
Following randomisation, participants will receive approximately 6 weeks of either standard dose radiotherapy (intensity-modulated radiation therapy or proton beam therapy, depending on age) OR escalated dose proton beam therapy. Following this, participants will be followed up for at least 2 years to monitor their condition. This includes pituitary, hormone level, tumour, neurocognitive, and ophthalmology assessments, as well as patient-reported quality of life outcomes and health economic measures.
- Being tested
- Standard dose Intensity-Modulated Radiation Therapy (IMRT), Standard dose Proton Beam Therapy (PBT), Escalated dose Proton Beam Therapy (PBT)
- Keywords
- Pituitary, Acromegaly, Cushing's, Radiotherapy, Proton Beam, Adenoma
- Medical subject headings
- Growth Hormone-Secreting Pituitary Adenoma, Pituitary ACTH Hypersecretion, Pituitary Neoplasms, Pituitary Diseases, Acromegaly, Adenoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard dose Intensity-Modulated Radiation Therapy (IMRT)Radiation
Standard dose IMRT (1.8Gy per fraction)
Standard dose Proton Beam Therapy (PBT)Radiation
Standard dose PBT (1.8Gy per fraction)
Escalated dose Proton Beam Therapy (PBT)Radiation
Escalated dose PBT (2Gy per fraction)
| Study group | Role | What they receive |
|---|---|---|
| Standard dose radiotherapy | Active comparator | Standard dose: 1.8Gy per fraction over 28 fractions.
* Participants aged 18-29 who are currently eligible for PBT via standard NHS indications will receive standard dose Proton Beam Therapy (PBT).
* Participants aged 30 and over will receive standard dose Intensity-Modulated Radiation Therapy (IMRT). Receives: Radiation: Standard dose Intensity-Modulated Radiation Therapy (IMRT); Radiation: Standard dose Proton Beam Therapy (PBT) |
| Escalated dose proton beam therapy | Experimental | Escalated dose: 2Gy per fraction over 28 fractions.
- Participants will receive escalated dose Proton Beam Therapy (PBT). Receives: Radiation: Escalated dose Proton Beam Therapy (PBT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to normalisation of hormone levels
Time to normalisation of hormone levels (i.e. growth hormone (GH) or insulin growth factor 1 (IGF-1)) following randomised treatment
Measured: From randomisation until normalisation (occurring within 2 years after completion of treatment).
Secondary outcomes (9)
Radiological treatment response
Data from MRI scans assessed for rates of stability, regression, and. progression. Overall response rate will be presented.
Measured: From baseline until 24 months after completion of treatment.
Radiological progression-free survival (PFS)
Progression-free survival (progression determined from an MRI scan).
Measured: From randomisation until progression (up to 2 years after completion of treatment) or death.
Medical therapies for hormone excess
The number and proportion of participants requiring new/changes to medical therapy for hormone excess at each visit.
Measured: From randomisation to completion of trial participation (2 years after completion of treatment)
Changes to hormone levels
Hormone levels relevant to the participant's disease (e.g. growth hormone [GH]) will be measured at each trial visit, summarised, and compared over time between treatment arms.
Measured: From randomisation to completion of trial participation (2 years after completion of treatment)
Safety and toxicity
Adverse events, assessed by CTCAE criteria v6.0.
Measured: Between randomisation and 6 months after completion of treatment for early toxicities, and until 2 years after completion of treatment for late toxicities.
Quality of life (CushingQoL/AcroQoL)
Quality of life (QoL) using either the CushingQoL/AcroQoL (as applicable depending on participant's condition) questionnaire.
Measured: From baseline until 24 months post completion of treatment.
Quality of Life (EQ-5D-5L)
Quality of Life (QoL) using results of participant-reported EQ-5D-5L questionnaires.
Measured: From baseline until 24 months post completion of treatment.
Pituitary insufficiency rates
Pituitary insufficiency rates (i.e. Growth hormone (GH), Adrenocorticotropic hormone (ACTH), Thyroid-Stimulating Hormone (TSH), Gonadotrophin, and Arginine Vasopressin (AVP) deficiencies) will be summarised and compared between arms.
Measured: From baseline until 24 months after completion of treatment.
Neurocognitive function and Neuro-ophthalmology outcomes
Measured: From randomisation until 24 months after completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2026
- Study startSep 2026 (estimated)
- Primary completionSep 2032 (estimated)
- Study completionSep 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acromegaly Due to Pituitary AdenomaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 82 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health and Care Research
- Responsible party
- Sponsor
- Investigators
- Michael Kosmin, Principal investigator, UCLH NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07813351
- Sponsor's protocol ID
- UCL/181514
- Other IDs
- NIHR168012, 369251
- Acronym
- PRESTO
- Status last verified
- Sep 2026
- First submitted
- 1 Sep 2026
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No