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Pasireotide Therapy in Patients With Nelson's Syndrome

Primary Purpose

Nelson Syndrome

Status

Terminated

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

Pasireotide

About this trial

This is an interventional treatment trial for Nelson Syndrome

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Barts and the London NHS Trust
The Christie Hospital NHS Foundation Trust
Oxford University Hospitals NHS Trust
Sheffield Teaching Hospitals NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pasireotide

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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?

Overall outcome measure

Does tumour volume correlate with somatostatin receptor expression?

Tumour volume from MRI scan

Full Information

NCT ID

NCT01617733

First Posted

June 8, 2012

Last Updated

November 1, 2016

Sponsor

Sheffield Teaching Hospitals NHS Foundation Trust

Collaborators

Novartis, The Christie NHS Foundation Trust, Oxford University Hospitals NHS Trust, Barts & The London NHS Trust

1. Study Identification

Unique Protocol Identification Number

NCT01617733

Brief Title

Pasireotide Therapy in Patients With Nelson's Syndrome

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Terminated

Why Stopped

Inadequate patient recruitment

Study Start Date

March 2011 (undefined)

Primary Completion Date

August 2015 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sheffield Teaching Hospitals NHS Foundation Trust

Collaborators

Novartis, The Christie NHS Foundation Trust, Oxford University Hospitals NHS Trust, Barts & The London NHS Trust

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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 Description

As above

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nelson Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pasireotide

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Pasireotide

Intervention Description

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

Primary Outcome Measure Information:

Title

Serum ACTH levels in patients with Nelson's syndrome.

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Tumour volume in patients with Nelson's syndrome.

Description

Time Frame

0 & 28 weeks

Title

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

Description

Overall outcome measure

Time Frame

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

Title

Does tumour volume correlate with somatostatin receptor expression?

Description

Tumour volume from MRI scan

Time Frame

0 & 28 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Newell-Price

Organizational Affiliation

Sheffield Teaching Hospitals NHS Foundation Trust

Official's Role

Principal Investigator

Facility Information:

Facility Name

Barts and the London NHS Trust

City

London

Country

United Kingdom

Facility Name

The Christie Hospital NHS Foundation Trust

City

Manchester

Country

United Kingdom

Facility Name

Oxford University Hospitals NHS Trust

City

Oxford

Country

United Kingdom

Facility Name

Sheffield Teaching Hospitals NHS Foundation Trust

City

Sheffield

ZIP/Postal Code

S10 2JF

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

29313180

Citation

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.

Results Reference

derived

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Pasireotide Therapy in Patients With Nelson's Syndrome

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