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
- Are there results?
- Not yet: the study is under way
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
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PRESTO: A Phase III Randomised Controlled Trial of Dose-escalated Proton Beam Therapy Versus Standard of Care Radiotherapy for Functioning Pituitary Tumours
- ClinicalTrials.gov ID
- NCT07813351
- Acronym / sponsor ID
- PRESTO / UCL/181514
- Keywords
- Pituitary, Acromegaly, Cushing's, Radiotherapy, Proton Beam, Adenoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 82 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- National Institute for Health and Care Research
- Study start
- Sep 2026 (estimated)
- Primary completion
- Sep 2032 (estimated)
- Study completion
- Sep 2032 (estimated)
- First posted
- 10 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard dose radiotherapy | Active comparator | Radiation: Standard dose Intensity-Modulated Radiation Therapy (IMRT), Radiation: Standard dose Proton Beam Therapy (PBT)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). |
| Escalated dose proton beam therapy | Experimental | Radiation: Escalated dose Proton Beam Therapy (PBT)Escalated dose: 2Gy per fraction over 28 fractions. - Participants will receive escalated dose Proton Beam Therapy (PBT). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard dose Intensity-Modulated Radiation Therapy (IMRT)Standard dose IMRT (1.8Gy per fraction) | Radiation | Standard dose radiotherapy |
| Standard dose Proton Beam Therapy (PBT)Standard dose PBT (1.8Gy per fraction) | Radiation | Standard dose radiotherapy |
| Escalated dose Proton Beam Therapy (PBT)Escalated dose PBT (2Gy per fraction) | Radiation | Escalated dose proton beam therapy |
Primary outcome
Time to normalisation of hormone levels
Time frame: From randomisation until normalisation (occurring within 2 years after completion of treatment).
Time to normalisation of hormone levels (i.e. growth hormone (GH) or insulin growth factor 1 (IGF-1)) following randomised treatment
9 secondary outcomes
Radiological treatment response
Time frame: From baseline until 24 months after completion of treatment.
Radiological progression-free survival (PFS)
Time frame: From randomisation until progression (up to 2 years after completion of treatment) or death.
Medical therapies for hormone excess
Time frame: From randomisation to completion of trial participation (2 years after completion of treatment)
Changes to hormone levels
Time frame: From randomisation to completion of trial participation (2 years after completion of treatment)
Safety and toxicity
Time frame: 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)
Time frame: From baseline until 24 months post completion of treatment.
Quality of Life (EQ-5D-5L)
Time frame: From baseline until 24 months post completion of treatment.
Pituitary insufficiency rates
Time frame: From baseline until 24 months after completion of treatment.
Neurocognitive function and Neuro-ophthalmology outcomes
Time frame: From randomisation until 24 months after completion of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
Related trials for Acromegaly Due to Pituitary Adenoma
Recruiting
Managing Pasireotide-associated Hyperglycaemia in Acromegaly With Ketogenic Diet
Acromegaly Due to Pituitary Adenoma, Hyperglycemia
Not yet recruitingObservational study
Ultrasound in Predicting Difficult Intubation in Acromegaly Patients
Acromegaly Due to Pituitary Adenoma, Difficult Intubation
RecruitingObservational study
Effects of Pasireotide Lar Therapy on Bone Metabolism
Acromegaly Due to Pituitary Adenoma, Acromegaly
Recruiting
KETOgenic Diet Therapy in Patients With ACROmegaly
Acromegaly Due to Pituitary Adenoma, Ketogenic Diet
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael Kosmin principal investigator
UCLH NHS Trust
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact PRESTO Trial Manager (+44 (0)20 7679 9860, ctc.presto@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to normalisation of hormone levels (time frame: From randomisation until normalisation (occurring within 2 years after completion of treatment).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.