Clinical Trial: Pasireotide Therapy in Patients With Nelson's Syndrome

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: An Open Label, Longitudinal Study of the Effects of Subcutaneous Acute and Chronic Pasireotide (som230) Therapy on Adrenocorticotrophic Hormone and Tumour Volume in Patients With

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.


Detailed Summary: As above
Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust

Current Primary Outcome: Serum ACTH levels in patients with Nelson's syndrome. [ Time Frame: 0, 2, 4, 8, 12, 16, 20, 24, 28 weeks ]

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



Original Primary Outcome: 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



Current Secondary Outcome:

  • Tumour volume in patients with Nelson's syndrome. [ Time Frame: 0 & 28 weeks ]

    Does Chronic Pasireotide Therapy Effect Tumour Volume?

    H0= Pasireotide will not reduce tumour volume in patients with Nelson's syndrome.

    H1= Pasireotide will reduce tumour volume in patients with Nelson's syndrome.

  • Is the Pasireotide Therapy Used in this Study Safe and Tolerable in Nelson's Patients? [ Time Frame: 0, 2, 4, 8, 12, 16, 20, 24, 28 weeks ]
    Overall outcome measure
  • Does tumour volume correlate with somatostatin receptor expression? [ Time Frame: 0 & 28 weeks ]
    Tumour volume from MRI scan


Original Secondary Outcome:

  • Tumour volume in patients with Nelson's syndrome.

    Does Chronic Pasireotide Therapy Effect Tumour Volume?

    H0= Pasireotide will not reduce tumour volume in patients with Nelson's syndrome.

    H1= Pasireotide will reduce tumour volume in patients with Nelson's syndrome.

  • Is the Pasireotide Therapy Used in this Study Safe and Tolerable in Nelson's Patients?
  • Does tumour volume correlate with somatostatin receptor expression?


Information By: Sheffield Teaching Hospitals NHS Foundation Trust

Dates:
Date Received: June 8, 2012
Date Started: March 2011
Date Completion:
Last Updated: November 1, 2016
Last Verified: November 2016