Dose Escalation Study of Pasireotide (SOM230) in Patients With Advanced Neuroendocrine Tumors (NETs)

Study Overview
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Brief Summary
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This study designed to determine the Maximum Tolerated Dose (MTD) for patients with advanced Neuroendocrine Tumors (NETs) and to characterize the safety, tolerability, Pharmacokinetics and preliminary efficacy of pasireotide LAR administered i.m. once every 28 days.

Official Title
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A Phase I, Multi-center, Open-label, Dose Escalation Study of Pasireotide (SOM230) LAR in Patients With Advanced Neuroendocrine Tumors (NETs)

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Drug: Pasireotide LAR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 yrs old, histologically confirmed advanced well or moderately differentiated neuroendocrine tumor/carcinoma unresectable metastatic NET tumor with measurable disease life expectancy ≥ 12 weeks Exclusion Criteria: Patients with CNS metastases who are neurologically unstable or requiring increasing doses of steroids to control their CNS disease patients with known hypersensitivity to somatostatin analogs patients with symptomatic cholelithiasis in the past 2 months patients with history of another known primary malignancy with exception of non-melanoma skin cancer or carcinoma in situ of uterine cervix patients with known history of hepatitis C or chronic active hepatitis B patients with diagnosis of HIV. 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<br> | Drug: Pasireotide LAR<br> <br> * Other names: SOM230;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the MTD/RP2D of pasireotide LAR when administered i.m. q28 days to patients with advanced NETs | Frequency of dose-limiting toxicities (DLTs) at each dose level associated with q28 days administration of pasireotide LAR during the first 2 treatment cycles. | Sequentiona 56 day cohorts until the MTD is determined | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assess the safety and tolerability of pasireotide LAR | Incidence of adverse drug events, overall and by severity and incidence of serious adverse events and laboratory abnormalities. Also, changes in laboratory assessments, electrocardiograms, Holter monitor, imaging for gallstones, and assessment of physical examinations such as vital signs | minimum of twelve 28 day cycles to approximately eighteen 28 day cycles | 
| assess the pharmacokinetics (PK) of pasireotide LAR | Pasireotide Cmax and Ctrough | minimum of twelve 28 day cycles to approximately eighteen 28 day cycles | 
| assess the pharmacodynamics (PD) of pasireotide LAR | Changes from baseline values in IGF-1, chromogranin A and neuron-specific enolase | minimum of twelve 28 day cycles to approximately eighteen 28 day cycles | 
| assess the preliminary efficacy (anti-tumor activity) of pasireotide LAR. | Disease control rate (CR+PR+SD as assessed by RECIST 1.0). Also measure progression free survival (PFS). | minimum of twelve 28 day cycles to approximately eighteen 28 day cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MTD, pasireotide, LAR, NETs, advanced neuroendocrine tumors