Pasireotide Therapy in Patients With Nelson's Syndrome

NCT01617733 | Terminated Phase 2 DMC

• 2 other identifiers: STH151642009-014457-33
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 4

Brief Summary

Nelson's syndrome, an expanding pituitary tumour, occurs in up to 30% of adults after bilateral adrenalectomy for Cushing's disease, for which no medical treatment exists. Plasma Adrenocorticotrophic hormone (ACTH) levels in these patients remain high, they are characteristically deeply pigmented, and may experience neurological effects as a consequence of the tumour. It is not known whether the tumour growth is due to the lack of cortisol feedback after adrenalectomy or whether the pituitary cells were preprogrammed to develop into a tumour. There is a real need for an effective medical management for Nelson's syndrome. This is especially true given the increasing data on the somewhat disappointing longterm outcome of transsphenoidal surgery, and the increasing use of aparoscopic bilateral adrenalectomy for failures of pituitary surgery or even as primary therapy for Cushing's disease. Therefore, it is likely that there will be increasing numbers of patients attending endocrine centres worldwide with Nelson's syndrome following bilateral adrenalectomy as part of their management for Cushing's disease. In view of this it is important to investigate all potential avenues for the treatment of Nelson's syndrome and translate any benefits to patients. This study, designed and initiated by the investigators, will assess if pasireotide reduces ACTH levels and tumour volume in patients with Nelson's syndrome. Patients will be recruited for a period of 32 weeks and receive 4 weeks of pasireotide twice daily and then 24 weeks of pasireotide long acting release therapy every 4 weeks. Over the 32 week protocol patients will make 12 visits for serial ACTH blood measurements and have 2 MRI scans to assess tumour volume.

Conditions

Nelson Syndrome

Outcome Measures

Primary Outcomes (1)

• Serum ACTH levels in patients with Nelson's syndrome.

  Early morning plasma ACTH sampled at 0, 1, 2, and 3 hours after morning hydrocortisone (HC) during 4 weeks of pasireotide 1200ug/day compared with levels at these respective time points found at baseline, and after chronic depot pasireotide 60mg i.m every 28 days: Complete success: Fall in pre-HC plasma ACTH \> 400ng/l, or 120 minutes after HC \>200ng/l Partial success: Fall in pre-HC plasma ACTH \< 399ng/l \>200ng/l, or 120 minutes after HC \<199ng/l \>100ng/l No success: Fall in pre-HC plasma ACTH \< 199ng/l, or 120 minutes after HC \<99ng/l

  0, 2, 4, 8, 12, 16, 20, 24, 28 weeks

Secondary Outcomes (3)

• Tumour volume in patients with Nelson's syndrome.

  0 & 28 weeks

• Is the Pasireotide Therapy Used in this Study Safe and Tolerable in Nelson's Patients?

  0, 2, 4, 8, 12, 16, 20, 24, 28 weeks

• Does tumour volume correlate with somatostatin receptor expression?

  0 & 28 weeks

Study Arms (1)

Pasireotide

EXPERIMENTAL

4 Weeks pasireotide 0.6mg s/c injections twice daily followed by 24 weeks treatment with pasireotide LAR 60mg every 28 days with dose reductions if poor tolerability is encountered

Drug: Pasireotide

Interventions

Pasireotide DRUG

4 Weeks pasireotide 0.6mg s/c injections twice daily followed by 24 weeks treatment with pasireotide LAR 60mg every 28 days with dose reductions if poor tolerability is encountered

Pasireotide

Eligibility Criteria

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

You may qualify if:

• To be verified at Visit one and confirmed at Visit two
• Male or female patients aged 18-80 years
• Signs and symptoms consistent with Nelson's Syndrome
• Biochemistry consistent with Nelsons syndrome: failure to suppress plasma ACTH to less than 200 pg/ml at 2 hours following morning dose of hydrocortisone
• Negative pregnancy test where applicable

You may not qualify if:

• Received any prior or current treatment with a pasireotide or other somatostatin analogue.
• Requires surgery for recent significant deterioration in visual fields or other neurological signs related to tumour mass.
• Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis, or persistent ALT, AST, alkaline phosphates 2X\> upper limit of normal, or total bilirubin 1.5X\> upper limit of normal.
• Patients with symptomatic cholelithiasis
• Abnormal clinical laboratory values considered by the Investigator to be clinically significant and which could affect the interpretation of the study results
• QTcF interval as measured by ECG \>480msecs
• Any current or prior medical condition that may, in the opinion of the Investigator, interfere with the conduct of the study or evaluation of the results.
• Female patients who are pregnant or lactating, or of childbearing potential and not practising a medically acceptable method of birth control. Medically acceptable methods include including the oral contraceptive pill, intrauterine devices, mechanical methods (e.g. vaginal diaphragm, vaginal sponge, or condom with permicidal jelly).
• History of alcohol or drug abuse in the sixmonth period prior to Visit 1, or who plan to take an investigational
• History of alcohol or drug abuse in the six month period prior to Visit 1, or who plan to take an investigational drug for another study during this study.
• History of noncompliance to medical regimes or who are considered potentially unreliable.
• Pituitary radiotherapy within the last 1 year prior to study entry.
• Unable to complete the entire study for any reason.

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• Novartis: collaborator
• The Christie NHS Foundation Trust: collaborator
• Oxford University Hospitals NHS Trust: collaborator
• Barts & The London NHS Trust: collaborator

Study Sites (4)

Barts and the London NHS Trust

London, United Kingdom

Location

The Christie Hospital NHS Foundation Trust

Manchester, United Kingdom

Location

Oxford University Hospitals NHS Trust

Oxford, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• Daniel E, Debono M, Caunt S, Girio-Fragkoulakis C, Walters SJ, Akker SA, Grossman AB, Trainer PJ, Newell-Price J. A prospective longitudinal study of Pasireotide in Nelson's syndrome. Pituitary. 2018 Jun;21(3):247-255. doi: 10.1007/s11102-017-0853-3.

  PMID: 29313180 DERIVED

MeSH Terms

Conditions

Nelson Syndrome

Interventions

pasireotide

Condition Hierarchy (Ancestors)

ACTH-Secreting Pituitary Adenoma; Pituitary Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Study Officials

• John Newell-Price

  Sheffield Teaching Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2012
• First Posted: June 12, 2012
• Study Start: March 1, 2011
• Primary Completion: August 1, 2015
• Study Completion: December 1, 2015
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

GB (4)