Efficacy and Safety of BEZ235 Compared to Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumors

Study Overview
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Brief Summary
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This was a multicenter, open label, randomized phase II study to evaluate the efficacy and safety of BEZ235 as compared to everolimus in patients with advanced, low to intermediate grade pancreatic neuroendocrine tumor (pNET).

Detailed Description
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Patients with advanced (unresectable or metastatic), low to intermediate grade (histologically confirmed well and moderately differentiated) pancreatic neuroendocrine tumor (pNET) were randomized to either BEZ235 or everolimus. The study was planned to include 140 patients, with 70 patients in the BEZ235 treatment group and 70 patients in the everolimus treatment group. An interim analysis was conducted on 62 randomized patients. The study was terminated as the BEZ235 treatment did not demonstrate a progression free survival advantage to everolimus treatment.

Official Title
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Randomized Phase II Study of BEZ235 or Everolimus in Advanced Pancreatic Neuroendocrine Tumors

Conditions
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Pancreatic Neuroendocrine Tumors (pNET)

Intervention / Treatment
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* Drug: BEZ235
* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced histologically confirmed well differentiated pancreatic neuroendocrine tumor Progressive disease within the last 12 months Measurable disease per RECIST Version 1.0 determined by multiphase MRI or triphasic CT Exclusion Criteria: Prior treatment with mTOR or PI3K inhibitors Patients with more than 2 prior systemic treatment regimens Previous cytotoxic chemotherapy, targeted therapy, or biotherapy within the last 4 weeks 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEZ235<br>Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily) | Drug: BEZ235<br>* BEZ235 400 mg bid p.o. (by mouth, twice daily)<br>|
| Active Comparator: Everolimus<br>Patients received Everolimus 10 mg qd p.o. (by mouth, daily) | Drug: Everolimus<br>* Everolimus 10 mg qd p.o. (by mouth, daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as the time from the date of randomization until the date of the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment. Patients will be followed up for the duration of the study and for an expected average of every 12 weeks after randomization. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of all target lesions, or unequivocal progression of non-target lesions, or the appearance of new lesions. | up to approx. 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Proportion of patients with a best overall response during the study of complete response (CR) or partial response (PR), based on the investigator assessment. 2. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for all target and non-target lesions, as well as new lesions as assessed by CT or MRI: Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of all target lesions; Overall Response (OR) = CR + PR. | up to approx. 18 months | 
| Overall Survival (OS) | Time from randomization to the date of death due to any cause | up to approx. 30 months | 
| Time to Treatment Failure (TTF) | Time from randomization to the date of the first of the following events:death due to any cause or progressive disease, treatment discontinuation due to toxicity or treatment discontinuation due to patient preference | up to approx. 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic, Neuroendocrine tumors, PNET, BEZ235, Everolimus