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

Primary Purpose

Pancreatic Neuroendocrine Tumors (pNET)

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BEZ235
Everolimus
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Neuroendocrine Tumors (pNET) focused on measuring Pancreatic, Neuroendocrine tumors, PNET, BEZ235, Everolimus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cedars Sinai Medical Center SC-3
  • University of Colorado Univ Colorado
  • University of Kentucky Univ Kebtucky
  • Montefiore Medical Center SC
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

BEZ235

Everolimus

Arm Description

Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)

Patients received Everolimus 10 mg qd p.o. (by mouth, daily)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Overall Survival (OS)
Time from randomization to the date of death due to any cause
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

Full Information

First Posted
June 25, 2012
Last Updated
March 9, 2016
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01628913
Brief Title
Efficacy and Safety of BEZ235 Compared to Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumors
Official Title
Randomized Phase II Study of BEZ235 or Everolimus in Advanced Pancreatic Neuroendocrine Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Terminated
Why Stopped
This trial was terminated based on an interim analysis as BEZ235 did not demonstrate a progression free survival advantage to everolimus treatment.
Study Start Date
October 2012 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Neuroendocrine Tumors (pNET)
Keywords
Pancreatic, Neuroendocrine tumors, PNET, BEZ235, Everolimus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
62 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BEZ235
Arm Type
Experimental
Arm Description
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
Arm Title
Everolimus
Arm Type
Active Comparator
Arm Description
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
Intervention Type
Drug
Intervention Name(s)
BEZ235
Intervention Description
BEZ235 400 mg bid p.o. (by mouth, twice daily)
Intervention Type
Drug
Intervention Name(s)
Everolimus
Intervention Description
Everolimus 10 mg qd p.o. (by mouth, daily)
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
up to approx. 18 months
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
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.
Time Frame
up to approx. 18 months
Title
Overall Survival (OS)
Description
Time from randomization to the date of death due to any cause
Time Frame
up to approx. 30 months
Title
Time to Treatment Failure (TTF)
Description
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
Time Frame
up to approx. 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Cedars Sinai Medical Center SC-3
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
University of Colorado Univ Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Kentucky Univ Kebtucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0098
Country
United States
Facility Name
Montefiore Medical Center SC
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Novartis Investigative Site
City
Lyon
ZIP/Postal Code
69437
Country
France
Facility Name
Novartis Investigative Site
City
Montpellier Cedex 5
ZIP/Postal Code
34298
Country
France
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Novartis Investigative Site
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse Cedex 4
ZIP/Postal Code
31054
Country
France
Facility Name
Novartis Investigative Site
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Facility Name
Novartis Investigative Site
City
Pisa
State/Province
PI
ZIP/Postal Code
56126
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00189
Country
Italy
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Kazan
ZIP/Postal Code
420029
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41013
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Hospitalet de LLobregat
State/Province
Catalunya
ZIP/Postal Code
08907
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Novartis Investigative Site
City
Luzern
ZIP/Postal Code
6000
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Glasgow
ZIP/Postal Code
G11 6NT
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Manchester
ZIP/Postal Code
M20 9BX
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Sheffield
ZIP/Postal Code
S10 2SJ
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
29242283
Citation
Salazar R, Garcia-Carbonero R, Libutti SK, Hendifar AE, Custodio A, Guimbaud R, Lombard-Bohas C, Ricci S, Klumpen HJ, Capdevila J, Reed N, Walenkamp A, Grande E, Safina S, Meyer T, Kong O, Salomon H, Tavorath R, Yao JC. Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor-Naive Advanced Pancreatic Neuroendocrine Tumors. Oncologist. 2018 Jul;23(7):766-e90. doi: 10.1634/theoncologist.2017-0144. Epub 2017 Dec 14.
Results Reference
derived

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

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