Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Syndrome

Nelson Syndrome

Adenoma

Pituitary Diseases

ACTH-Secreting Pituitary Adenoma

Pituitary Neoplasms

Endocrine Gland Neoplasms

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

ACTH-secreting Pituitary Adenoma

All Drugs and Chemicals

Hormones

Pasireotide

Adrenocorticotropic Hormone

Hormone Antagonists

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

John Newell-Price

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.

Pasireotide Therapy in Patients With Nelson's Syndrome

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

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

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.

Novartis

The Christie NHS Foundation Trust

Oxford University Hospitals NHS Trust

Barts & The London NHS Trust

Sheffield Teaching Hospitals NHS Foundation Trust

Digestive System Diseases

Heart and Blood Diseases

Pancreatic Neoplasms

Cushing Syndrome

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Cardiac Complexes, Premature

ACTH Syndrome, Ectopic

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Paraneoplastic Syndromes

Adrenocortical Hyperfunction

Adrenal Gland Diseases

Pancreatic Cancer

Cushing's Syndrome

Hyperadrenalism

Patients received pasireotide LAR at 60 mg approximately once every 28 days for 6 months during the core treatment period and additional treatment cycles up to a total of 48 months during the extension phase.

Investigational drug pasireotide LAR was supplied in vials with 20 mg or 40 mg powder and 2 mL vehicle was supplied in ampoules for reconstitution.

pasireotide LAR

Novartis Pharmaceuticals

This study will assess the effectiveness and safety of pasireotide long-acting release in patients who have rare tumors of neuroendocrine origin.

Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin

An Open Label, Multicenter, Single Arm Study of Pasireotide LAR in Patients With Rare Tumors of Neuroendocrine Origin

The primary efficacy endpoint was defined as the percentage of responders at Month 6 among pooled PNET patients (insulinoma, gastrinoma, VIPoma, and glucagonoma). A responder was defined as a patient who either attained normalization or had a greater than 50% reduction from baseline of the level of the primary biochemical tumor marker at Month 6 (M6). Four insulinoma pts were excluded from analysis because of unavailability of normal ranges for the associated primary biochemical tumor marker (insulin-to-glucose ratio). One patient with VIPoma with a normal baseline was also excluded. As a result, only 20 out of 25 patients with PNET were included in the assessment of the primary endpoint, which was less than the planned sample size of 34. Therefore, the primary objective could not be assessed with sufficient power. Patients with missing Month 6 assessment were considered as non-responders. Responder analyses are reported only for indications with minimum of 6 patients.

Percentage of responders for each of the 10 NET indications considered in the study. Responder analyses were performed for an indication only if there were at least 6 patients in the efficacy analyzable set. For all other individual indications, the numbers of patients in the efficacy analyzable sets were less than 6 and therefore no responder analyses were carried out for these indications.

Percentage of responders for each of the 10 NET indications considered in the study. Responder analyses were performed for an indication only if there were at least 6 patients in the efficacy analyzable set. For all other individual indications, the numbers of patients in the efficacy analyzable sets were less than 6 and therefore no responder analyses were carried out for these indications. The probability of success was a chance that the true responder rate was greater than 15%) for the indications gastrinoma, prolactinoma, and Nelson's syndrome.

Specific primary biochemical tumor markers were used to assess the efficacy of pasireotide in PNETs. A Month 6 responder was defined as the patients who either attained normalization or greater than 50% reduction from baseline in the level of the primary biochemical tumor marker at Month 6. One gastrinoma patient had a missing primary tumor marker value at Month 6, but had a Month 5 assessment done on Day 141, which fell within the allowed window period for Month 6.

Specific primary biochemical tumor markers were used to assess the efficacy of pasireotide in PNETs. A Month 6 responder was defined as the patients who either attained normalization or greater than 50% reduction from baseline in the level of the primary biochemical tumor marker at Month 6.

Six patients with Nelson's syndrome met the responder's criteria of attaining normalization or a reduction of more than 50% in primary tumor marker at Month 6.

Pancreatic NETs (PNETs)

Pituitary NETs (PiNETs)

Ectopic ACTH-secrting Tumors (EAS)

Nelson's syndrome is based on disease specific primary biochemical tumor markers. Patients received pasireotide LAR at 60 mg approximately once every 28 days for 6 months during the core treatment period and additional treatment cycles up to a total of 48.

Nelsons Syndrome

All patients received pasireotide LAR at 60 mg approximately once every 28 days for 6 months during the core treatment period and additional treatment cycles up to a total of 48 months during the extension phase. Patients included patients with pancreatic neuroendocrine tumors (PNETs), pituitary NETs (PiNETs), Ectopic ACTH-secreting tumor (EAS) \& Nelson's syndrome.

Pasireotide LAR 60mg

Age, Continuous

Sex: Female, Male

The full analysis set (FAS) consisted of all enrolled patients who received at least one dose of pasireotide LAR.

Study Director

Gastrinoma

VIpoma

Glucagonoma

The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN. Patients with baseline primary biochemical tumor marker levels either missing at baseline or missing ULN or baseline value ≤ ULN were excluded.

Percentage of Responders at Month 6 - Pooled Pancreatic NETs (PNETs)

Prolactinoma

based on disease specific primary biochemical tumor markers. Patients received pasireotide LAR at 60 mg approximately once every 28 days for 6 months during the core treatment period and additional treatment cycles up to a total of 48 months during the extension phase.

Nelson's Syndrome

The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN.

Percentage of Responders at Month 6 - Individual NETs

Percentage of Responders With Probability of Success at Month 6 - Individual NETs

Baseline

Month 6

All PNETS (Gastrinoma)

The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN. Responder analysis are reported only for indications with minimum of 6 patients. Patients with missing Month 6 assessment were considered as non-responders.

PNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker

All PiNETS (Prolactinoma)

PiNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker

Nelson's syndrome is associated with local tumor extension or invasion following a therapeutic bilateral adrenalectomy

Nelson's Syndrome: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pasireotide Therapy in Patients With Nelson's Syndrome	NCT01617733	Nelson Syndrome	Pasireotide	18 Years - 80 Years	Sheffield Teaching Hospitals NHS Foundation Trust
Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin	NCT00958841	Pancreatic Neop... Pituitary Neopl... Nelson Syndrome Ectopic ACTH Sy...	pasireotide LAR	18 Years -	Novartis
Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin	NCT00958841	Pancreatic Neop... Pituitary Neopl... Nelson Syndrome Ectopic ACTH Sy...	pasireotide LAR	18 Years -	Novartis

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