A Study of Pasireotide in People With Prolactinoma

Inclusion Criteria:

1. Age 18 or older

2. Male and female patients with prolactinomas with at least one of the followingcriteria:

• Clinical intolerance due to adverse events on DA treatment, preventingcontinued treatment.

• Contraindication to DA treatment (e.g., patients requiring dopamine antagonisttherapy or other therapy that is contraindicated).

• Tumor resistance to DA, defined as <50% decrease in longest diameter, orprogression in tumor size and/or lack of prolactin normalization with at least 2 mg per week, or maximally tolerated dose, of cabergoline or bromocriptine.Patients with a partial response to DA, including a prolactin reduction but notnormalization on treatment, will be included, and will continue DA during thestudy.

3. Patients are not considered candidates for surgery (e.g., poor surgical candidates,inoperable tumors, patients who refuse surgical treatment, or for whom surgery isdeemed not appropriate treatment).

4. For patients with a history of pituitary radiation, the following criteria must bepresent:

• At least 6 months must have elapsed from the time of the most recent radiationtreatment to the time of enrollment, and

• Stable or up trending serum prolactin levels and/or evidence of tumor growthsince completion of radiation.

5. At least 8 weeks washout of prior first-generation somatostatin receptor ligandtherapy (octreotide or lanreotide).

6. Patients on temozolomide will need a washout period of at least 3 weeks.

7. Patients on carboplatin, cisplatin or etoposide will need a washout period of atleast 4 weeks.

8. Patients on protein kinase inhibitors (e.g., everolimus, lapatinib) will need awashout period of at least 5 half-lives or 2 weeks, whichever in longer.

9. In general, at least 4 weeks must have elapsed from any other anticancer drugtherapy (e.g., bevacizumab).

10. Stable or lower dose of DA (cabergoline or bromocriptine) for at least one month forthose patients continuing DA treatment, i.e. DA dose may not be escalated duringtrial enrollment.

11. Screening laboratory values must meet the following criteria:

• WBC ≥ 2000/μL

• Neutrophils ≥ 1500/μL

• Platelets ≥ 100 x103/μL

• Hemoglobin > 9.0 g/dL

• AST/ALT ≤ 3 x ULN

• Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who canhave total bilirubin < 3.0 mg/dL)

• Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min usingthe Cockcroft-Gault formula

12. Karnofsky Performance Status (KPS) 70 or above

13. Measurable tumor by RECIST V1.1 criteria, ≥ 10 mm.

14. Women of childbearing potential (WOCBP) must use appropriate methods ofcontraception while participating in the trial until 30 days after the follow-upperiod.

• WOCBP is defined as any female who has experienced menarche and who has notundergone surgical sterilization (hysterectomy or bilateral oophorectomy) orwho is not postmenopausal. Menopause is defined clinically as 12 months ofamenorrhea in a woman over 45 in the absence of other biological orphysiological causes. Women who are not of childbearing potential are notrequired to use contraception.

• Women of childbearing potential must have a negative serum or urine pregnancytest upon study entry.

15. Men who are sexually active with women of childbearing potential must use adequatecontraception while participating in the trial. Men who are surgically sterile orazoospermia do not require contraception.

Exclusion Criteria:

1. Additional pituitary tumor directed therapy, including temozolomide, everolimus,lapatinib, or cytotoxic chemotherapy

2. Concurrent malignancy except non-melanoma skin cancer

3. Any pituitary surgery within 14 days of enrollment.

4. Patients with poorly controlled diabetes as defined by HBA1c >9% or not optimallytreated for diabetes mellitus as judged by the investigator

5. Patients who are not euthyroid as judged by the investigator

6. Patient with liver disease such as cirrhosis, chronic active hepatitis, or chronicpersistent hepatitis, or patients with serum ALT and/or AST >3x ULN, or totalbilirubin >1.5 x ULN

7. Patients with QTc > 500 ms

8. History of intolerance or resistance to pasireotide

9. Women who are pregnant or breast-feeding

10. Inability to undergo radiographic surveillance

11. Inability to provide informed consent