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

Phase 3Not Yet RecruitingNCT07813351

University College, London82 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acromegaly Due to Pituitary Adenoma Cushing's Disease Pituitary Adenoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

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

Secondary Outcomes

Radiological treatment response

Data from MRI scans assessed for rates of stability, regression, and. progression. Overall response rate will be presented.

Time frame: From baseline until 24 months after completion of treatment.

Radiological progression-free survival (PFS)

Progression-free survival (progression determined from an MRI scan).

Time frame: 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.

Time frame: 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.

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

Safety and toxicity

Adverse events, assessed by CTCAE criteria v6.0.

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)

Quality of life (QoL) using either the CushingQoL/AcroQoL (as applicable depending on participant's condition) questionnaire.

Time frame: 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.

Time frame: 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.

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