Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin

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

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

Conditions
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Pancreatic Neoplasm, Pituitary Neoplasm, Nelson Syndrome, Ectopic ACTH Syndrome

Intervention / Treatment
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* Drug: pasireotide LAR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and Female Patients at least 18 years old Patient who have rare tumors of neuroendocrine origin, such as tumors of the: pancreas pituitary glands Nelson syndrome ectopic-ACTH secreting tumor Patients who have failed standard of care treatment or for whom no standard of care treatment exist Signed Informed Consent Exclusion Criteria: Patients with active gallbladder disease Patients with any ongoing or planned anti-neoplastic or interferon therapy Poorly controlled diabetes mellitus Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pasireotide LAR 60mg<br>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. | Drug: pasireotide LAR<br>* 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.<br>* Other names: SOM230;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders at Month 6 - Pooled Pancreatic NETs (PNETs) | 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders at Month 6 - Individual NETs | 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. | 6 months | 
| Percentage of Responders With Probability of Success at Month 6 - Individual NETs | 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. | 6 months | 
| PNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | 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. | Baseline, month 6 | 
| PiNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | 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. | Baseline, month 6 | 
| Nelson's Syndrome: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | 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. | Baseline, month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rare tumors of neuroendocrine origin, NETs of the pancreatic, Pituitary NETs, EAS Tumors, Nelson's Syndrome, Pancreatic neoplasm, pituitary neoplasm, Nelson Syndrome, ectopic ACTH syndrome, pasireotide LAR, PNETs, PiNETS