Evaluation of Cabergoline in the Management of Non-Functioning Pituitary Adenomas: A Randomized Controlled Trial

The primary objective of this study is to evaluate the effect of medical treatment with **cabergoline** in patients with non-functioning pituitary adenomas (NFPAs). This is clinically relevant as NFPAs are common pituitary tumors that do not secrete hormones, and their management often involves surgical intervention. The potential use of cabergoline, a dopamine agonist, could offer a non-surgical treatment option, potentially reducing tumor size or halting progression, thereby improving patient outcomes and quality of life.

The clinical trial focuses on evaluating the effect of cabergoline in patients with **non-functioning pituitary adenomas**. The study population includes both male and female participants, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. The trial does not involve a vulnerable population. Participants are selected based on specific criteria, including those with a previously untreated non-functioning pituitary macroadenoma, characterized by a largest diameter of at least 10 mm with demonstrated growth on repeated MRI scans or proximity to the chiasma opticum. Additionally, individuals with a residual non-functioning pituitary adenoma post-surgery, with a largest diameter of at least 5 mm, that is either extrasellar or has documented growth after surgical treatment, are eligible. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the effect of **cabergoline** in patients with non-functioning pituitary adenomas. This study is a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is expected to span a duration of two years, with the estimated end date set for December 13, 2024. Participants will be involved in the study for a maximum treatment period of 24 months, during which they will receive **cabergoline** in the form of oral tablets, with a maximum daily dose of 0.29 mg and a total dose not exceeding 208 mg.

The sequence of study visits begins with an inclusion visit, where participants are screened based on specific criteria, including having a previously untreated non-functioning pituitary macroadenoma or a residual adenoma post-surgery. Follow-up visits will be conducted periodically to monitor the primary endpoint, which is the change in tumor volume, and secondary endpoints, such as the need for surgical or radiation treatment, changes in pituitary function, and visual field defects. The end-of-study visit will assess the overall outcomes and any adverse effects experienced by the participants.

Participants may be subject to early termination from the study if they experience significant adverse effects, fail to comply with the study protocol, or if the study is discontinued for any reason. The trial aims to provide valuable insights into the efficacy of **cabergoline** in managing non-functioning pituitary adenomas, potentially influencing future treatment protocols for this condition.

The clinical trial involves the administration of **cabergoline**, marketed under the name Dostinex 0.5 mg tabletter, as the experimental medication. Cabergoline is a dopamine agonist used in the treatment of non-functioning pituitary adenomas. The pharmaceutical form of the medication is a tablet, and it is administered orally. The maximum daily dose of cabergoline is 0.29 mg, with a total maximum dose of 208 mg over the course of the treatment. The treatment period is set to a maximum of 24 months. The medication is produced by Pfizer AS and is classified under the ATC code G02CB03. The active substance, cabergoline, is of chemical origin.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the effects of cabergoline in the specified patient population. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to assess the therapeutic impact of cabergoline on non-functioning pituitary adenomas, with no additional medications or interventions being utilized as part of the study protocol.

Efficacy in the clinical trial evaluating the effect of **cabergoline** in non-functioning pituitary adenomas will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the change in tumor volume over the two-year study period. This includes measuring the percentage and absolute change in tumor volume, as well as identifying the number of patients experiencing significant tumor shrinkage or growth, defined as a change of ≥ 10% or ≥ 2 mm in at least one dimension.

Secondary endpoints will include the need for surgical and/or radiation treatment during the study, the development of new pituitary failure or changes in pituitary function, and the emergence of new or altered visual field defects or other cranial nerve affections. Additionally, the change in the tumor's distance to the chiasma opticum will be measured in millimeters. The response of gonadotropins (FSH, LH) and/or their subunits, particularly the α-subunit, will also be evaluated. A possible correlation between tumor size response and hormone levels, as well as changes during treatment, will be explored.