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

Phase 2
Terminated
Conditions
Pancreatic Neuroendocrine Tumors (pNET)
Interventions
Registration Number
NCT01628913
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

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

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
62
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
BEZ235BEZ235Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
EverolimusEverolimusPatients received Everolimus 10 mg qd p.o. (by mouth, daily)
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS)up to approx. 18 months

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.

Secondary Outcome Measures
NameTimeMethod
Objective Response Rateup to approx. 18 months

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.

Overall Survival (OS)up to approx. 30 months

Time from randomization to the date of death due to any cause

Time to Treatment Failure (TTF)up to approx. 18 months

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

Trial Locations

Locations (5)

Cedars Sinai Medical Center SC-3

🇺🇸

Los Angeles, California, United States

Montefiore Medical Center SC

🇺🇸

Bronx, New York, United States

University of Colorado Univ Colorado

🇺🇸

Aurora, Colorado, United States

Novartis Investigative Site

🇬🇧

Sheffield, United Kingdom

University of Kentucky Univ Kebtucky

🇺🇸

Lexington, Kentucky, United States

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