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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 )

Tracking Information
First Submitted Date  ICMJE June 25, 2012
First Posted Date  ICMJE June 27, 2012
Results First Submitted Date  ICMJE August 19, 2015
Results First Posted Date  ICMJE April 7, 2016
Last Update Posted Date April 7, 2016
Study Start Date  ICMJE October 2012
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 9, 2016)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 26, 2012)
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 8 weeks after randomisation
Change History Complete list of historical versions of study NCT01628913 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2016)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2012)
  • Type, frequency and severity of adverse events [ Time Frame: at minimum at each study visit and up to approx. 18 months ]
    Safety will be determined by type, frequency and severity of adverse events per CTCAEv4.03 and type, frequency and severity of laboratory toxicities per CTCAEv4.03. Patients will be followed up for the duration of the study
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of BEZ235 Compared to Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumors
Official Title  ICMJE Randomized Phase II Study of BEZ235 or Everolimus in Advanced Pancreatic Neuroendocrine Tumors
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Neuroendocrine Tumors (pNET)
Intervention  ICMJE
  • Drug: BEZ235
    BEZ235 400 mg bid p.o. (by mouth, twice daily)
  • Drug: Everolimus
    Everolimus 10 mg qd p.o. (by mouth, daily)
Study Arms  ICMJE
  • Experimental: BEZ235
    Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
    Intervention: Drug: BEZ235
  • Active Comparator: Everolimus
    Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
    Intervention: Drug: Everolimus
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 21, 2014)
62
Original Estimated Enrollment  ICMJE
 (submitted: June 26, 2012)
140
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Italy,   Netherlands,   Russian Federation,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries Australia,   Brazil,   India,   Poland
 
Administrative Information
NCT Number  ICMJE NCT01628913
Other Study ID Numbers  ICMJE CBEZ235Z2401
CBEZ235Z2401 ( Other Identifier: Novartis )
2012-000769-19
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP