PRESTO: A Phase III Randomised Controlled Trial of Dose-escalated Proton Beam Therapy Versus Standard of Care Radiotherapy for Functioning Pituitary Tumours (PRESTO)

September 7, 2026 updated by: University College, London

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 Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

82

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Neuropathological confirmation of growth hormone (acromegaly) or ACTH (Cushing's disease) secreting pituitary adenoma after neurosurgical intervention.
  2. Ongoing hormonal hypersecretion as defined by local and age-specific normal range values without hormone supressing medication (may need washout).
  3. Multidisciplinary team meeting recommendation for fractionated radiotherapy.
  4. Karnofsky performance status ≥70.
  5. Age ≥18 years.
  6. Agreement to travel to a proton beam therapy centre (i.e. UCLH or The Christie) as required.
  7. Written informed consent.
  8. Agreement to be followed up at a local PRESTO trial site.

Exclusion Criteria:

  1. Women who are pregnant or breast feeding.
  2. Prior cranial or head and neck radiotherapy treatment, including Stereotactic radiosurgery (SRS).
  3. Unsuitability or intolerability of MRI scans.
  4. Severe active comorbidities that limit compliance with trial requirements.
  5. Prior invasive malignancy unless disease free interval of ≥3 years.
  6. Unable to travel to the PBT centres as per trial requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard dose radiotherapy

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).
Radiation: Standard dose Intensity-Modulated Radiation Therapy (IMRT)
Standard dose IMRT (1.8Gy per fraction)
Radiation: Standard dose Proton Beam Therapy (PBT)
Standard dose PBT (1.8Gy per fraction)
Experimental: Escalated dose proton beam therapy

Escalated dose: 2Gy per fraction over 28 fractions.

- Participants will receive escalated dose Proton Beam Therapy (PBT).
Radiation: Escalated dose Proton Beam Therapy (PBT)
Escalated dose PBT (2Gy per fraction)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From randomisation until normalisation (occurring within 2 years after completion of treatment).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiological treatment response
Time Frame: From baseline until 24 months after completion of treatment.
Data from MRI scans assessed for rates of stability, regression, and. progression. Overall response rate will be presented.
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.
Progression-free survival (progression determined from an MRI scan).
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)
The number and proportion of participants requiring new/changes to medical therapy for hormone excess at each visit.
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)
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.
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.
Adverse events, assessed by CTCAE criteria v6.0.
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 (QoL) using either the CushingQoL/AcroQoL (as applicable depending on participant's condition) questionnaire.
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.
Quality of Life (QoL) using results of participant-reported EQ-5D-5L questionnaires.
From baseline until 24 months post completion of treatment.
Pituitary insufficiency rates
Time Frame: From baseline until 24 months after completion of treatment.
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.
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
From randomisation until 24 months after completion of treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Health Economic Evaluation
Time Frame: From 6 months prior to baseline until 2 years after completion of trial treatment.
The health economic analysis will calculate the mean incremental cost per quality-adjusted life-years (QALYs) gained on using dose-escalated proton beam therapy compared to standard dose radiotherapy.
From 6 months prior to baseline until 2 years after completion of trial treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Collaborators

National Institute for Health and Care Research

Investigators

  • Principal Investigator: Michael Kosmin, UCLH NHS Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

September 1, 2032

Study Completion (Estimated)

September 1, 2032

Study Registration Dates

First Submitted

September 1, 2026

First Submitted That Met QC Criteria

September 7, 2026

First Posted (Actual)

September 10, 2026

Study Record Updates

Last Update Posted (Actual)

September 10, 2026

Last Update Submitted That Met QC Criteria

September 7, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCL/181514
  • NIHR168012 (Other Grant/Funding Number: National Institute for Health and Care Research (NIHR))
  • 369251 (Other Identifier: IRAS)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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