Dopamine Agonist Treatment of Non-functioning Pituitary Adenomas

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

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.

Study Overview

• Status: Recruiting
• Conditions: Adenoma; Pituitary Neoplasms
• Intervention / Treatment: Drug: cabergoline

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Stine L Fougner, MD PhD; Email: stine.fougner@ntnu.no
• Study Contact Backup: Name: Sven M Carlsen, md phd; Email: sven.carlsen@ntnu.no

Study Locations

• Norway
  • Oslo, Norway
    • Recruiting
    • Department of Endocrinology, Akershus University hospital
  • Trondheim, Norway, 7006
    • Recruiting
    • Department of Endocrinology, St. Olavs Hospital
    • Contact: Stine L Fougner, MD PhD; Email: stine.fougner@ntnu.no
• Sweden
  • Gøteborg, Sweden
    • Recruiting
    • Sahlgrenska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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: Dostinex; FCE 21336; galastop; Cabaser; Cabaseril; cabergoline diphosphate
No Intervention: observation; visits and controls as usual

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Collaborators: Norwegian University of Science and Technology
• Investigators: Principal Investigator: Sven M Carlsen, prof md, Norwegian University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: November 5, 2014
• First Submitted That Met QC Criteria: November 12, 2014
• First Posted (Estimate): November 13, 2014

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: January 19, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: cabergoline; dopamine agonists
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Adenoma; Pituitary Neoplasms; Pituitary Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Cabergoline
• Other Study ID Numbers: 2012/677; 2012-001338-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No