Clinical Trial: BEZ235 Phase II Trial in Patients With Advanced Pancreatic Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multicenter, Two Stage, Phase II Study, Evaluating the Efficacy of Oral BEZ235 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in the Treatment of Patients With Advanced Pancreatic Neuroendo

Brief Summary:

This is a Phase II study in 2 stages, evaluating BEZ235 plus best supportive care (BSC) versus placebo plus BSC in patients with advanced pancreatic neuroendocrine tumors (pNET) after failure of mTOR inhibitor therapy.

Study design: This was a Phase II, two-stage, multicenter study, where Stage 1 was a single arm, open label design and Stage 2 was planned to be a randomized, double-blind study.

However, at the end of Stage 1, the futility was met and hence the Stage 2 was not initiated.


Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Stage 1 - Progression Free Survival (PFS) Rate Analysis at 16 Weeks as Per Local Radiology Review [ Time Frame: 16 weeks after the first BEZ235 administration. ]

PFS rate at 16 weeks was defined as a binary variable. Patients were considered as 'progression free' after 16 weeks if they had an overall lesion response of complete response (CR) partial response ('PR) or stable disease (SD)' and "progressed" if they had an overall lesion response of 'Progressive disease (PD) at the scan which occurred on day 105 after start of treatment, or later. Patients whose 16 weeks tumor assessment was unknown, missing or outside the window was not considered as 'progression free' and was considered a "failure" and counted only in the denominator for the estimation of the 16 week progression free rate.


Original Primary Outcome:

  • Stage 1 - Progression Free Survival (PFS) at 16 weeks [ Time Frame: 16 weeks after the first BEZ235 administration. ]
    Stage 1 Progression Free Survival is defined as the number of progression free patients divided by the total number of patients in the full analysis set. PFS will be assessed according to local radiological assessment per modified RECIST v1.1
  • Stage 2 - Progression Free Survival (PFS) [ Time Frame: from the randomization date until the date of first documented progression or date of death from any cause which ever come first, assessed up to 30 months. ]
    Stage 2 Progression Free Survival is defined as the time from the randomization date until objective tumor progression or death from any cause. PFS will be assessed according to local radiological assessment per modified RECIST v1.1


Current Secondary Outcome:

  • Stage 1- Overall Response Rate (ORR) [ Time Frame: Baseline, every 8 weeks up to 31 months ]
    Overall Response rate was defined as the proportion of patients with a best overall response of complete response or partial response, based on investigator's assessment as per RECIST criteria version 1.1. Based on futility analysis conducted at the end of stage 1, stage 2 was not initiated.
  • Stage 1 - Disease Control Rate [ Time Frame: Baseline, every 8 weeks up to 31 months ]
    Disease control rate was defined as the proportion of patients with a best overall response of Complete Response, Partial response, or Stable disease, based on the investigator's assessment per RECIST version 1.1. Based on futility analysis conducted at the end of stage 1, stage 2 was not initiated.


Original Secondary Outcome:

  • Stage1&2 - Frequency and severity of Adverse Events (AEs) [ Time Frame: three times per month during first month of therapy, then twice a month and 30 days after study treatment termination. ]
    Measure the safety and tolerability of BEZ235 therapy by monitoring the concomitant medications, abnormal laboratory values, physical examination and other safety data as appropriate.
  • Stage 1&2- Evaluate Overall Response Rate [ Time Frame: Baseline, every 8 weeks. ]
    Overall Response rate is defined as the proportion of patients with a best overall response of complete response or partial response, based on investigator's assessment as per RECIST criteria version 1.1.
  • Stage 1&2- Disease Control rate [ Time Frame: Baseline, every 8 weeks ]
    Disease control rate is defined as the proportion of patients with a best overall response of Complete Response, Partial response, or Stable disease, based on the investigator's assessment per RECIST version 1.1.
  • Stage 1&2- Measure Duration of Response [ Time Frame: Baseline, evry 8 weeks. ]
    Duration of overall response is defined only for the responder subset: patients with confirmed complete response or partial response based on investigator's assessment. It is the elapsed time between the date of first documented response and the following date of event defined as the first documented progression or death due to underlying cancer, per RECIST version 1.1..
  • Stage 2- Overall survival [ Time Frame: up to approximately 28 months ]
    Time from randomisation to the date of death due to any cause.


Information By: Novartis

Dates:
Date Received: July 6, 2012
Date Started: November 2012
Date Completion:
Last Updated: April 19, 2016
Last Verified: April 2016