Intervention: Pasireotide
Trial phase: Phase 2 | Phase 3
ATC code: H01CB05
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Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 12
Group description: For non-cured patients with resistant prolactinomas , MRI will be performed immediately before and six months after the onset of pasireotide . The efficacy will be evaluated by prolactin dosage every month.

For patients harboring a NFPA, treatment will be started at least 3 months after neurosurgery. In this case, the drug efficacy will be evaluated by MRI six months after pasireotide.

Pasireotide: The patients with NFPA will be randomized into two groups: (A) the first one will be treated with pasireotide at the dosage of 900 µg s.c. twice a day for 6 months; (B) the second one, with cabergoline 3 mg/week for six months.

The patients with resistant prolactinomas will be treated with pasireotide at the dosage of 600 µg s.c. twice a day. After four weeks of treatment, the patients who normalize serum prolactin level will be maintained at the same dosage, the others who do not achieve normal prolactin level will have their dosage raised to 900 µg s.c. twice a day for six months.
Eligibility criteria:
Inclusion Criteria

Male or female patients aged 18 years or greater
Patients with confirmed diagnosis of NFPA evidenced by: magnetic resonance imaging (MRI) confirmation of pituitary adenoma and No pituitary tumoral hormone hypersecretion
Patients with no previous medical treatment
Patients who had been submitted to surgery but not cured. Lack of cure is defined as presence of remnant tumor on MRI at least three months after surgery (without any possible misinterpretation of postsurgical changes)
Patients with confirmed diagnosis of resistant prolactinoma by lack of prolactin normalization with a tolerated cabergoline dosage during 12 weeks
Patients who had been submitted to surgery due to resistance to cabergoline and not cured. Lack of cure is defined as lack of serum prolactin normalization or complete removal of tumor load
Patients who signed the informed consent

Exclusion Criteria

Previous pituitary radiotherapy
High risk for transsphenoidal surgery
Patients with symptomatic cholelithiasis
Diabetic patients on antidiabetic medications those fasting blood glucose is poorly controlled as evidenced by HbA1C > 8%
Patients with abnormal coagulation (prothrombin time (PT) or partial thromboplastin time (PTT) elevated by 30% above normal limits);
Patients receiving anticoagulants that affect PT or PTT
Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, history of acute MI less than one year prior to study entry or clinically significant impairment in cardiovascular function
Patients with risk factors for torsade de pointes, i.e. patients with a baseline corrected QT interval (QTc) > 480 ms, hypokalemia, family history of long QT syndrome, and concomitant medications known to prolong QT interval
Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with (alanine aminotransferase) ALT/ (aspartate aminotransferase) AST more than 2 X upper limit of normal (ULN), serum creatinine > 2.0 X ULN, serum bilirubin > 2.0 X ULN, serum albumin < 0.67 X lower limit of normal (LLN)
Patients with white blood cell (WBC) < 3 X 109/L; Hgb < LLN; Platelet count (PLT) < 100 X 109/L
Patients who have any current or prior medical condition that can interfere with the conduct of the study or the evaluation of its results in the opinion of the investigator
Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method for birth control. Female patients must use barrier contraception with condoms. If oral contraception is used, the patient must have been practicing this method for at least two months prior to enrollment and must agree to continue the oral contraceptive throughout the course of the study and for one month after the last dose of study drug. Male patients who are sexually active are required to use condoms during the study and for 1 month afterwards
Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving pasireotide