Dopamine Agonist Treatment of Non-functioning Pituitary Adenomas

Sponsor

St. Olavs Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT02288962

Collaborator

Norwegian University of Science and Technology (Other)

Enrollment

Locations

Arms

138

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pituitary Neoplasms Adenoma	Drug: cabergoline	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 1, 2014

Anticipated Primary Completion Date :

May 1, 2022

Anticipated Study Completion Date :

May 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: cabergoline 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 Other Names: galastop FCE 21336 Cabaser Dostinex Cabaseril cabergoline diphosphate
No Intervention: observation visits and controls as usual

Arm

Intervention/Treatment

Experimental: cabergoline

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

Other Names:

galastop

FCE 21336

Cabaser

Dostinex

Cabaseril

cabergoline diphosphate

No Intervention: observation

visits and controls as usual

Outcome Measures

Primary Outcome Measures

change in tumour volume during the main study of two years [2 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)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Department of Endocrinology, Akershus University hospital	Oslo	Norway
2	Department of Endocrinology, St. Olavs Hospital	Trondheim	Norway	7006
3	Sahlgrenska University Hospital	Gøteborg	Sweden