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NCT Number: NCT07813351

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

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.

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Key information

Conditions

Acromegaly Due to Pituitary Adenoma Acromegaly Adenoma Bone Diseases Bone Diseases, Endocrine Brain Diseases Brain Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms Cushing's Disease Endocrine Gland Neoplasms Endocrine System Diseases Growth Hormone-Secreting Pituitary Adenoma Hyperpituitarism Hypothalamic Diseases Hypothalamic Neoplasms Musculoskeletal Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Nervous System Diseases Nervous System Neoplasms Pituitary ACTH Hypersecretion Pituitary Adenoma Pituitary Diseases Pituitary Neoplasms Supratentorial Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

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)

Primary outcomes

  1. 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

Secondary outcomes

  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Neurocognitive function and Neuro-ophthalmology outcomes

    Time frame: From randomisation until 24 months after completion of treatment

Other outcomes

  1. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

PRESTO Trial Manager

CONTACT

[email protected]

+44 (0)20 7679 9860

Sponsors and collaborators

Lead sponsor

University College, London

Other

Collaborators

  • National Institute for Health and Care Research

Registry information

Acronym: PRESTO

Important dates

Study start
2026
Primary completion
2032
Study completion
2032
First posted
Sep 10, 2026
Registry last updated
Sep 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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