Safety and Tolerability of Pasireotide LAR in Combination With Everolimus in Advanced Metastatic NETs

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of pasireotide LAR in combination with everolimus in advanced metastatic gastroenteropancreatic or pulmonary neuroendocrine Tumors (NET).

Official Title
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An Open-label Phase I Study Evaluating the Safety and Tolerability of Pasireotide LAR in Combination With Everolimus in Advanced Metastatic NETs - The COOPERATE-1 Study

Conditions
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Gastroenteropancreatic Neuroendocrine Tumor of the Pulmonary ot Gastroenteropancreatic System

Intervention / Treatment
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* Drug: Pasireotide LAR followed by Pasireotide LAR + Everolimus
* Drug: Everolimus followed by Pasireotide LAR + Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of grade 1/2 advanced pulmonary or gastroenteropancreatic neuroendocrine tumor Progressive disease within last 12 months (only patients with nonfunctional tumors) Documented liver metastasis Measurable disease per RECIST determined by multiphase MRI or triphasic CT Exclusion Criteria: Previous treatment with radiolabeled somatostatin analogs within 12 months prior to reporting baseline symptoms Previous treatment with mTOR inhibitors or pasireotide Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study Women who are pregnant or lactating 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Functional tumors, pre-treated<br> | Drug: Pasireotide LAR followed by Pasireotide LAR + Everolimus<br> <br> |
| Experimental: Functional tumors, treatment naïve<br> | Drug: Pasireotide LAR followed by Pasireotide LAR + Everolimus<br> <br> |
| Experimental: Nonfunctional tumors, pretreated 1<br> | Drug: Pasireotide LAR followed by Pasireotide LAR + Everolimus<br> <br> |
| Experimental: Nonfunctional tumors, pretreated 2<br> | Drug: Everolimus followed by Pasireotide LAR + Everolimus<br> <br> |
| Experimental: Nonfunctional tumors, treatment-naïve 1<br> | Drug: Pasireotide LAR followed by Pasireotide LAR + Everolimus<br> <br> |
| Experimental: Nonfunctional tumors, treatment-naïve 2<br> | Drug: Everolimus followed by Pasireotide LAR + Everolimus<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety and tolerability profile of pasireotide LAR in combination with everolimus in patients with advanced metastatic NET |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety and tolerability of pasireotide LAR and/or everolimus in patients with advanced metastatic NET |  | 15 months | 
| To assess pharmacokinetic exposures of pasireotide LAR and everolimus during monotherapy and in combination therapy |  | 15 months | 
| To assess potential drug-drug interactions between pasireotide and everolimus during combination therapy |  | 12 months | 
| To assess symptom control (bowel movements and flushing episodes) with pasireotide LAR in combination with everolimus in patients with functioning tumors |  | 15 months | 
| To assess the biochemical response (chromograninA, CgA) to pasireotide LAR in combination with everolimus |  | 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoid tumor,, Gastroenteropancreatic Neuroendocrine Tumors,, Pulmonary Neuroendocrine Tumors,, pasireotide LAR,, SOM230 LAR,, everolimus,, RAD001,, Advanced Neuroendocrine Tumor,, Gastroenteropancreatic System