Acromegaly Due to Pituitary Adenoma, Cushing's Disease, Pituitary Adenoma
Conditions
Keywords
Pituitary, Acromegaly, Cushing's, Radiotherapy, Proton Beam, Adenoma
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.
Interventions
RADIATIONStandard dose Intensity-Modulated Radiation Therapy (IMRT)
Standard dose IMRT (1.8Gy per fraction)
RADIATIONStandard dose Proton Beam Therapy (PBT)
Standard dose PBT (1.8Gy per fraction)
RADIATIONEscalated dose Proton Beam Therapy (PBT)
Escalated dose PBT (2Gy per fraction)
Sponsors
University College, London
National Institute for Health and Care Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to normalisation of hormone levels | 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
| Measure | Time frame | Description |
|---|---|---|
| Radiological treatment response | 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. |
| Radiological progression-free survival (PFS) | From randomisation until progression (up to 2 years after completion of treatment) or death. | Progression-free survival (progression determined from an MRI scan). |
| Medical therapies for hormone excess | 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. |
| Changes to hormone levels | 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. |
| 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. | Adverse events, assessed by CTCAE criteria v6.0. |
| Quality of life (CushingQoL/AcroQoL) | 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. |
| Quality of Life (EQ-5D-5L) | From baseline until 24 months post completion of treatment. | Quality of Life (QoL) using results of participant-reported EQ-5D-5L questionnaires. |
| Pituitary insufficiency rates | 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. |
| Neurocognitive function and Neuro-ophthalmology outcomes | From randomisation until 24 months after completion of treatment | — |
Contacts
CONTACTPRESTO Trial Manager
PRINCIPAL_INVESTIGATORMichael Kosmin
UCLH NHS Trust
Outcome results
None listed