A Study of Pasireotide in People With Prolactinoma

Pasireotide Treatment for Patients With Prolactinomas Who Need Treatment Beyond Dopamine Agonist Therapy

The researchers are doing this study to find out whether pasireotide is an effective treatment for people with prolactinoma who cannot receive dopamine agonist therapy. Another purpose of this study is to find out whether pasireotide is a safe treatment for people with prolactinoma.

Inclusion Criteria:

1. Age 18 or older

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

   • Clinical intolerance due to adverse events on DA treatment, preventing continued treatment.
   • Contraindication to DA treatment (e.g., patients requiring dopamine antagonist therapy or other therapy that is contraindicated).
   • Tumor resistance to DA, defined as <50% decrease in longest diameter, or progression 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 not normalization on treatment, will be included, and will continue DA during the study.

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

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

   • At least 6 months must have elapsed from the time of the most recent radiation treatment to the time of enrollment, and
   • Stable or up trending serum prolactin levels and/or evidence of tumor growth since completion of radiation.

5. At least 8 weeks washout of prior first-generation somatostatin receptor ligand therapy (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 at least 4 weeks.

8. Patients on protein kinase inhibitors (e.g., everolimus, lapatinib) will need a washout 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 drug therapy (e.g., bevacizumab).

10. Stable or lower dose of DA (cabergoline or bromocriptine) for at least one month for those patients continuing DA treatment, i.e. DA dose may not be escalated during trial 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 can have total bilirubin < 3.0 mg/dL)
    • Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min using the 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 of contraception while participating in the trial until 30 days after the follow-up period.

    • WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. Women who are not of childbearing potential are not required to use contraception.
    • Women of childbearing potential must have a negative serum or urine pregnancy test upon study entry.

15. Men who are sexually active with women of childbearing potential must use adequate contraception while participating in the trial. Men who are surgically sterile or azoospermia 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 optimally treated 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 chronic persistent hepatitis, or patients with serum ALT and/or AST >3x ULN, or total bilirubin >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