Pasireotide LAR Therapy of Silent Corticotroph Pituitary Tumors

NCT02749227 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: AAAQ6255CSOM230GUS44T
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pituitary Tumor; ACTH-producing Pituitary Tumour

Keywords

Clinically non-functioning pituitary adenomas (CNFAs); silent corticotroph adenomas

Outcome Measures

Primary Outcomes (1)

• Change in Plasma Proopiomelanocortin (POMC) Levels

  This is to measure the effect of Pasireotide LAR (long-acting release) treatment.

  Baseline, 12 months

Secondary Outcomes (1)

• Change in Pituitary Tumor Volume

  Baseline, 12 months

Study Arms (1)

Pasireotide LAR Therapy

EXPERIMENTAL

Subjects will receive Pasireotide LAR monthly. Safety labs and Pituitary MRI will be performed.

Drug: Pasireotide LAR

Interventions

Pasireotide LAR DRUG

Pasireotide LAR (SIGNIFOR® LAR) is a somatostatin analog indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option. It is a long acting release injectable suspension for intramuscular use. The starting dose is Pasireotide LAR 40 mg/month intramuscular (IM), this will be increased to 60 mg/month at 6 months if a fall in POMC levels and/or tumor shrinkage are not attained.

Also known as: Signifor LAR

Pasireotide LAR Therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

• 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

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Neuroendocrine Unit and Pituitary Center, Columbia University

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Pituitary Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Pituitary Diseases; Endocrine System Diseases

Limitations and Caveats

The study was terminated due to poor enrollment.

Results Point of Contact

• Title: Pamela U. Freda, MD
• Organization: Columbia University

puf1@cumc.columbia.edu

212-305-2254

Study Officials

• Pamela Freda, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine at the Columbia University Medical Center, Dept of Medicine Endocrinology

Study Record Dates

• First Submitted: April 20, 2016
• First Posted: April 22, 2016
• Study Start: July 10, 2017
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: April 27, 2021
• Results First Posted: April 27, 2021

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)