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

NCT07813351 | Not Yet Recruiting Phase 3 DMC

• 3 other identifiers: UCL/181514NIHR168012369251
• Study Type: interventional
• Target: 82
• Locations: 0 countries
• Sites: N/A

Brief 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 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.

Conditions

Acromegaly Due to Pituitary Adenoma; Cushing's Disease; Pituitary Adenoma

Keywords

Pituitary; Acromegaly; Cushing's; Radiotherapy; Proton Beam; Adenoma

Outcome Measures

Primary Outcomes (1)

• 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

  From randomisation until normalisation (occurring within 2 years after completion of treatment).

Secondary Outcomes (9)

• Radiological treatment response

  From baseline until 24 months after completion of treatment.

• Radiological progression-free survival (PFS)

  From randomisation until progression (up to 2 years after completion of treatment) or death.

• Medical therapies for hormone excess

  From randomisation to completion of trial participation (2 years after completion of treatment)

• Changes to hormone levels

  From randomisation to completion of trial participation (2 years after completion of treatment)

• Safety and toxicity

  Between randomisation and 6 months after completion of treatment for early toxicities, and until 2 years after completion of treatment for late toxicities.

Other Outcomes (1)

• Health Economic Evaluation

  From 6 months prior to baseline until 2 years after completion of trial treatment.

Study Arms (2)

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).

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).

Radiation: Escalated dose Proton Beam Therapy (PBT)

Interventions

Standard dose Intensity-Modulated Radiation Therapy (IMRT) RADIATION

Standard dose IMRT (1.8Gy per fraction)

Standard dose radiotherapy

Standard dose Proton Beam Therapy (PBT) RADIATION

Standard dose PBT (1.8Gy per fraction)

Standard dose radiotherapy

Escalated dose Proton Beam Therapy (PBT) RADIATION

Escalated dose PBT (2Gy per fraction)

Escalated dose proton beam therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University College, London: lead
• National Institute for Health and Care Research: collaborator

MeSH Terms

Conditions

Growth Hormone-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Pituitary Diseases; Acromegaly; Adenoma

Interventions

Radiotherapy, Intensity-Modulated; Proton Therapy

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Hyperpituitarism; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Heavy Ion Radiotherapy

Study Officials

• Michael Kosmin

  UCLH NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

PRESTO Trial Manager

CONTACT

+44 (0)20 7679 9860; ctc.presto@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2026
• First Posted: September 10, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2032
• Study Completion (Estimated): September 1, 2032
• Last Updated: October 1, 2026

Record last verified: 2026-09