Clinical trial NCT03271918: Cabergoline in Nonfunctioning Pituitary Adenomas
Official title: Dopamine Agonist Cabergoline in Residual Clinically Nonfunctioning Pituitary Adenoma After Transphenoidal Surgery: A Single Center, Open Label and Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pituitary Adenoma
Nonfunctioning Pituitary Adenoma
Keywords: Pituitary Adenoma
Dopaminergic Agonist
Nonfunctioning Pituitary Adenoma
Cabergoline
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2017-09-05
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Single Center, Open Label and Randomized Clinical Trial.
Primary purpose: TREATMENT

Brief summary: Clinically nonfunctioning pituitary adenoma remains the only pituitary tumor subtype for which no effective medical therapy is available or recommended. We will evaluate the use of cabergoline in a clinical trial, in order to define the efficacy of this treatment in nonfunctioning pituitary adenoma.

Detailed description: Nonfunctioning pituitary adenomas (NFPA) are common tumors of sellar region characterized by the absence of clinically hormonal pituitary secretion. These adenomas are typically not diagnosed until they become very large and cause compressive neurologic symptons (e.g. visual impairment or cranial nerve palsy). Most of them are able to synthesized gonadotropins but not secreted it.

Transsphenoidal surgical resection is the first-choice therapy in NFPA. However, complete removal is difficult and tumor rest is very common. In these cases, the pragmatic use of radiotherapy is effective to reduce residual tumor growth or recurrence, but it is related with severe side effects. Another possibility is the clinical observation, or wait-to-see approach, but it is associated with tumor progression: 40% in 5-10 years. The efficacy of some medical treatment are not defined yet.

Since the identification of dopaminergic and somatostatinergic receptors in NFPA, the pharmacological treatment of the NFPA has been considered as a possibility for treatment. To date, clinical use of dopamine agonist (DA) in NFPA patients has been evaluated in some studies. However, these studies present modest and inconclusive results and the DA role in the NPFA management remains undefined.

In this study, the investigators plan a clinical trial designed to investigate the efficacy of cabergoline in NFPA individuals with remaining tumor after primary neurosurgery. These results could help to define the efficacy of DA in NFPA management.

Eligibility criteria: Inclusion Criteria:

* presence of pituitary tumor rest at 6 months after neurosurgery
* absence of previous hormonal pituitary hypersecretion
* absence of previous radiotherapy and/or radiosurgery
* Histopathological exam showing pituitary adenoma

Exclusion Criteria:

* ACTH immunoexpression at histopathological exam
* presence of previous radiotherapy and/or radio surgery
* psychotic psychiatric disease
* moderate or severe alterations in cardiac valves

Primary outcomes:
measure: tumor shrinkage
timeFrame: 24 months
Secondary outcomes:
measure: Tumor rest stabilization
timeFrame: 24 months
Other outcomes:
measure: Cardiovascular Safety
timeFrame: 24 months
Locations:
city: São Paulo
country: Brazil
facility: Laboratorio de Investigacoes Medicas 25
state: SP
Study officials:
affiliation: Instituto do Coracao
name: Rafael L Batista, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vieira Neto L, Wildemberg LE, Moraes AB, Colli LM, Kasuki L, Marques NV, Gasparetto EL, de Castro M, Takiya CM, Gadelha MR. Dopamine receptor subtype 2 expression profile in nonfunctioning pituitary adenomas and in vivo response to cabergoline therapy. Clin Endocrinol (Oxf). 2015 May;82(5):739-46. doi: 10.1111/cen.12684. Epub 2015 Jan 8.
citation: Greenman Y, Cooper O, Yaish I, Robenshtok E, Sagiv N, Jonas-Kimchi T, Yuan X, Gertych A, Shimon I, Ram Z, Melmed S, Stern N. Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists. Eur J Endocrinol. 2016 Jul;175(1):63-72. doi: 10.1530/EJE-16-0206. Epub 2016 May 5.
citation: Batista RL, Musolino NRC, Cescato VAS, da Silva GO, Medeiros RSS, Herkenhoff CGB, Trarbach EB, Cunha-Neto MB. Cabergoline in the Management of Residual Nonfunctioning Pituitary Adenoma: A Single-Center, Open-Label, 2-Year Randomized Clinical Trial. Am J Clin Oncol. 2019 Feb;42(2):221-227. doi: 10.1097/COC.0000000000000505.