Trial record 4 of 4 for:    PITUITARY ADENOMA, ACTH-SECRETING

Pasireotide Therapy in Patients With Nelson's Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Sheffield Teaching Hospitals NHS Foundation Trust
Sponsor:
Collaborators:
Novartis
Christie Hospital NHS Foundation Trust
Oxford University Hospitals NHS Trust
Barts & The London NHS Trust
Information provided by (Responsible Party):
Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01617733
First received: June 8, 2012
Last updated: August 23, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Nelson Syndrome
Drug: Pasireotide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Nelson's Syndrome

Resource links provided by NLM:


Further study details as provided by Sheffield Teaching Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • Serum ACTH levels in patients with Nelson's syndrome. [ Time Frame: 0, 2, 4, 8, 12, 16, 20, 24, 28 weeks ] [ Designated as safety issue: No ]

    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



Secondary Outcome Measures:
  • Tumour volume in patients with Nelson's syndrome. [ Time Frame: 0 & 28 weeks ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: Yes ]
    Overall outcome measure

  • Does tumour volume correlate with somatostatin receptor expression? [ Time Frame: 0 & 28 weeks ] [ Designated as safety issue: No ]
    Tumour volume from MRI scan


Estimated Enrollment: 17
Study Start Date: March 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pasireotide
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
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

Detailed Description:

As above

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01617733

Locations
United Kingdom
Barts and the London NHS Trust Recruiting
London, United Kingdom
Contact: Scott Akker       s.a.akker@qmul.ac.uk   
Principal Investigator: Scott Akker         
The Christie Hospital NHS Foundation Trust Recruiting
Manchester, United Kingdom
Contact: Peter Trainer       peter.trainer@manchester.ac.uk   
Principal Investigator: Peter Trainer         
Oxford University Hospitals NHS Trust Not yet recruiting
Oxford, United Kingdom
Contact: Ashley Grossman       ashley.grossman@ocdem.ox.ac.uk   
Principal Investigator: Ashley Grossman         
Sheffield Teaching Hospitals NHS Foundation Trust Recruiting
Sheffield, United Kingdom, S10 2JF
Contact: John Newell-Price       j.newellprice@sheffield.ac.uk   
Principal Investigator: John Newell-Price         
Sponsors and Collaborators
Sheffield Teaching Hospitals NHS Foundation Trust
Novartis
Christie Hospital NHS Foundation Trust
Oxford University Hospitals NHS Trust
Barts & The London NHS Trust
Investigators
Principal Investigator: John Newell-Price Sheffield Teaching Hospitals NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01617733     History of Changes
Other Study ID Numbers: STH15164, 2009-014457-33
Study First Received: June 8, 2012
Last Updated: August 23, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
ACTH-Secreting Pituitary Adenoma
Pituitary Neoplasms
Pituitary Diseases
Nelson Syndrome
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Adrenocorticotropic Hormone
Beta-Endorphin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014