Dopamine Agonist Treatment of Non-functioning Pituitary Adenomas

Study Overview
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Brief Summary
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Due to lack of hormone overproduction in non-functioning pituitary adenomas (NFPAs), only the symptomatic adenomas or large adenomas with proven growth and risk for symptoms in near future will undergo pituitary surgery. The remaining adenomas are monitored regularly. Operation of these large adenomas will rarely remove all tumour tissue, and there is also a risk of worsening of pituitary function. Often, adenomas with the highest growth potential are operated several times and some also need radiation therapy, providing additional risk for pituitary failure. Unlike some of the hormone-producing adenomas, there is no established pharmacological treatment for NFPAs. However, there are a few non-randomized studies suggesting that treatment with dopamine agonists may slow growth, and also induce tumour shrinkage. At present, cabergoline is the dopamine agonist most widely used in the treatment of pituitary adenomas secreting prolactin. Aim is to study the effect of medical treatment with cabergoline in non-functioning pituitary adenomas on the change in tumour volume.

Official Title
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Dopamine Agonist Treatment of Non-functioning Pituitary Adenomas (NFPAs) - a Randomized Controlled Trial

Conditions
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Pituitary Neoplasms, Adenoma

Intervention / Treatment
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* Drug: cabergoline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A previously untreated non-functioning pituitary macroadenoma (largest diameter ≥ 10 mm) with either demonstrated growth on repeated MRI scans or ≤ 2 mm distance to chiasma opticum, or: a residual non-functioning pituitary adenoma after surgery (largest diameter ≥ 5 mm) that is either extrasellar and/or with documented growth after surgical treatment of a non-functioning pituitary macroadenoma Exclusion Criteria: Clear indication for surgery at the time of inclusion Previous radiation therapy Pituitary surgery the last 6 months Previous apoplexy/bleeding in the adenoma Pregnancy or lactation Contraindications for cabergoline treatment (Known cardiac valvular disease, known pulmonal, pericardial or retroperitoneal fibrosis, clinical significant liver insufficiency, use of medications that interact with cabergoline unfit to participate due to any other reason

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cabergoline<br>Target dose for cabergoline is 2 mg/week.The medication is administered in the evening to minimize side effects. If intolerable side effects occur despite this, it may be necessary to treat with a lower dose than 2 mg per week. Treatment scheme: 0.5 mg x 1 per week the first 2 weeks, then 0.5 mg x 2 per week the next 2 weeks, then 1 + 0.5 mg per week the next 2 weeks, then 1 mg x 2 per week (target dose) for the rest of the study | Drug: cabergoline<br> <br> * Other names: cabergoline diphosphate;|
| No Intervention: observation<br>visits and controls as usual | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in tumour volume during the main study of two years | This includes the percentage and absolute change in tumour volume, but also the number of patients with significant tumour shrinkage or tumour growth (defined by ≥ 10 % or ≥ 2 mm shrinkage/growth in at least one dimension) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| need for surgical and/or radiation treatment |  | up till 2 years | 
| changed pituitary function | measured by analysis of blood tests, basal and stimulation tests | up till 2 years | 
| change in tumour's distance to chiasma opticum in mm | as measured by analysis of MRI images | up till 2 years | 
| development of cardiac valvulopathy | as measured by analysis of echo cardiography | up till 2 years | 
| impulse control disorder | as measured by questionnaire visual files: clinical evaluation by ophthalmologist and perimetry | up till 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dopamine agonists, cabergoline