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

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ClinicalTrials.gov Identifier: NCT01628913

Recruitment Status : Terminated (This trial was terminated based on an interim analysis as BEZ235 did not demonstrate a progression free survival advantage to everolimus treatment.)

First Posted : June 27, 2012

Results First Posted : April 7, 2016

Last Update Posted : April 7, 2016

Sponsor:

Information provided by (Responsible Party):

Novartis ( Novartis Pharmaceuticals )

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).

Condition or disease	Intervention/treatment	Phase
Pancreatic Neuroendocrine Tumors (pNET)	Drug: BEZ235 Drug: Everolimus	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	62 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Randomized Phase II Study of BEZ235 or Everolimus in Advanced Pancreatic Neuroendocrine Tumors
Study Start Date :	October 2012
Actual Primary Completion Date :	September 2014
Actual Study Completion Date :	September 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Everolimus

Genetic and Rare Diseases Information Center resources: Neuroendocrine Tumor Pancreatic Neuroendocrine Tumor Neuroepithelioma Pancreatic Cancer

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: BEZ235 Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)	Drug: BEZ235 BEZ235 400 mg bid p.o. (by mouth, twice daily)
Active Comparator: Everolimus Patients received Everolimus 10 mg qd p.o. (by mouth, daily)	Drug: Everolimus Everolimus 10 mg qd p.o. (by mouth, daily)

Outcome Measures

Primary Outcome Measures :

Progression Free Survival (PFS) [ Time Frame: 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 :

Objective Response Rate [ Time Frame: up 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) [ Time Frame: up to approx. 30 months ]
Time from randomization to the date of death due to any cause
Time to Treatment Failure (TTF) [ Time Frame: 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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01628913

Locations

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United States, California
Cedars Sinai Medical Center SC-3
Los Angeles, California, United States, 90048
United States, Colorado
University of Colorado Univ Colorado
Aurora, Colorado, United States, 80045
United States, Kentucky
University of Kentucky Univ Kebtucky
Lexington, Kentucky, United States, 40536-0098
United States, New York
Montefiore Medical Center SC
Bronx, New York, United States, 10467
France
Novartis Investigative Site
Lyon, France, 69437
Novartis Investigative Site
Montpellier Cedex 5, France, 34298
Novartis Investigative Site
Paris, France, 75015
Novartis Investigative Site
Reims, France, 51092
Novartis Investigative Site
Toulouse Cedex 4, France, 31054
Italy
Novartis Investigative Site
Bologna, BO, Italy, 40138
Novartis Investigative Site
Pisa, PI, Italy, 56126
Novartis Investigative Site
Roma, RM, Italy, 00189
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1105 AZ
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Russian Federation
Novartis Investigative Site
Kazan, Russian Federation, 420029
Spain
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Hospitalet de LLobregat, Catalunya, Spain, 08907
Novartis Investigative Site
Madrid, Spain, 28034
Novartis Investigative Site
Madrid, Spain, 28046
Switzerland
Novartis Investigative Site
Luzern, Switzerland, 6000
United Kingdom
Novartis Investigative Site
Glasgow, United Kingdom, G11 6NT
Novartis Investigative Site
London, United Kingdom, NW3 2QG
Novartis Investigative Site
London, United Kingdom, SE1 9RT
Novartis Investigative Site
Manchester, United Kingdom, M20 9BX
Novartis Investigative Site
Sheffield, United Kingdom, S10 2SJ

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

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Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Salazar R, Garcia-Carbonero R, Libutti SK, Hendifar AE, Custodio A, Guimbaud R, Lombard-Bohas C, Ricci S, Klümpen 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-Naïve Advanced Pancreatic Neuroendocrine Tumors. Oncologist. 2018 Jul;23(7):766-e90. doi: 10.1634/theoncologist.2017-0144. Epub 2017 Dec 14.

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Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01628913
Other Study ID Numbers:	CBEZ235Z2401 CBEZ235Z2401 ( Other Identifier: Novartis ) 2012-000769-19
First Posted:	June 27, 2012 Key Record Dates
Results First Posted:	April 7, 2016
Last Update Posted:	April 7, 2016
Last Verified:	March 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):


Pancreatic Neuroendocrine tumors PNET BEZ235 Everolimus

Additional relevant MeSH terms:

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Neuroendocrine Tumors Adenoma, Islet Cell Neoplasms Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Nerve Tissue Adenoma Neoplasms, Glandular and Epithelial Pancreatic Neoplasms Digestive System Neoplasms	Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Everolimus Dactolisib Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs

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