Pasireotide LAR Therapy of Silent Corticotroph Pituitary Tumors

Stopped early · Phase 2

Conditions studied: Pituitary Tumor, ACTH-producing Pituitary Tumour

In brief

This is a phase II, open-label, 12-month pilot study in 10 patients with silent corticotroph pituitary tumors testing the hypotheses that Pasireotide long-acting release (LAR) treatment of patients with silent corticotroph pituitary tumors and elevated plasma Proopiomelanocortin (POMC) levels will reduce plasma POMC levels and this will be associated with a reduction in pituitary tumor size. Pasireotide LAR 40 mg will be administered monthly. Baseline and monthly visits on therapy will monitor plasma levels of POMC, other pituitary function, safety labs, glucose tolerance, physical examination, and visual fields. Pituitary magnetic resonance imaging (MRI) will be done at baseline, 6 months and 12 months of therapy. The eligible patient population will consist of adult patients with known silent corticotroph pituitary tumors and elevated plasma levels of POMC.

Key facts

Study ID

NCT02749227

Run by

Columbia University

People needed

4

Starts

2017-07-10

Expected to finish

2020-03-31

Last updated by the study team

2021-04-27

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
• Adults (males and females) with a diagnosis of a clinically nonfunctioning pituitary tumor of the silent corticotroph tumor type (i.e., positive adrenocorticotropin (ACTH) staining on immunohistochemical staining of the pituitary tumor obtained at surgery)
• Plasma POMC level > upper limit of normal
• Prior pituitary tumor surgery with residual or recurrent pituitary tumor visible on MRI scan that is ≥ 5 mm from the optic chiasm.
• Surgical resection of the pituitary adenoma must have occurred two or more months prior to enrollment
• If patients have undergone pituitary radiotherapy they must have completed their course of radiotherapy at least 2 months prior to study screening
• No prior somatostatin analog therapy
• No concurrent use of dopamine agonist therapy
• No active malignancy
• Stable pituitary hormone supplements (x 2 months) prior to baseline visit
• Sign and date an informed consent document indicating that the subject has been informed of and agrees to all pertinent aspects of the trial

You may not qualify if…

• Subjects must not meet any of the following exclusion criteria to be eligible for enrollment into the study:
• Patients with Cushing's disease (biochemical evidence of hypercortisolism)
• Patients with compression of the optic chiasm causing any visual field defect that requires surgical intervention
• Diabetic patients with poor glycemic control as evidenced by HbA1c >8%
• Patients who are hypothyroid or adrenally insufficient and not on adequate replacement therapy
• Patients with symptomatic cholelithiasis and acute or chronic pancreatitis
• Patients with risk factors for torsade de pointes, i.e., patients with a baseline QTcF (Fridericia's Correction Formula value) >450 ms in males, and >460 ms in females
• Hypokalaemia, hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT syndrome or concomitant medications with known risk of Torsades de pointes (TdP). Drugs with possible risk of TdP should be avoided whenever feasible
• 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 myocardial infarction (MI) less than one year prior to study entry or clinically significant impairment in cardiovascular function
• Concomitant disease(s) that could prolong the QT interval such as autonomic neuropathy (caused by diabetes or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure
• Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 2.0 X upper limit of normal (ULN), serum bilirubin >2.0 X ULN
• Presence of Hepatitis B surface antigen (HbsAg) or Hepatitis C antibody test (anti-HCV)
• Patients with serum creatinine >2.0 X ULN
• Patients with white blood cell (WBC) count <3 X 109/L; Hb 90% < lower limit of normal (LLN); platelet (PLT) count <100 X 109/L
• Patients with the presence of active or suspected acute or chronic uncontrolled infection
• Patients who have undergone major surgery/surgical therapy for any cause within 4 weeks prior screening
• Patients with abnormal coagulation (PT and/or activated partial thromboplastin time (APTT) elevated by 30% above normal limits) or patients receiving anticoagulants that affect PT (prothrombin time) or APTT (activated partial thromboplastin time)
• History of syncope or family history of idiopathic sudden death
• History of immunocompromise, including a positive HIV test result (ELISA and Western blot)
• Sexually active males unless they use a condom during intercourse while taking drug and for 3 months following last dose of pasireotide and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and 3 months following last dose of pasireotide. Highly effective contraception methods include:
• Total abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
• Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject

Where it is running

• Neuroendocrine Unit and Pituitary Center, Columbia University — New York, New York, United States

Full record on ClinicalTrials.gov

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