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

April 19, 2016 updated by: Novartis Pharmaceuticals

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 Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Wien, Austria, A-1090
        • Novartis Investigative Site
  • Belgium
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
  • France
      • Lyon, France, 69437
        • Novartis Investigative Site
      • Villejuif Cedex, France, 94805
        • Novartis Investigative Site
  • Germany
      • Essen, Germany, 45147
        • Novartis Investigative Site
  • Italy
    • FI
      • Firenze, FI, Italy, 50134
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20133
        • Novartis Investigative Site
      • Milano, MI, Italy, 20141
        • Novartis Investigative Site
  • Netherlands
      • Rotterdam, Netherlands, 3015 CE
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28041
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Hospitalet de LLobregat, Catalunya, Spain, 08907
        • Novartis Investigative Site
  • United Kingdom
      • Manchester, United Kingdom, M20 4BX
        • Novartis Investigative Site
  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University SC
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute GastrointestionalCancer Clinic
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center SC-2
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State Comprehensive Cancer Center/James Cancer Hospital SC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Unresectable or metastatic, histologically confirmed low or intermediate grade pancreatic neuroendocrine tumor with radiological evidence of disease progression since last treatment
  • Refractory disease to treatment with mTOR inhibitor
  • Measurable disease per RECIST Version 1.1 using Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)
  • Prior or concurrent therapy with SSA is permitted; a stable dose at least 2 months prior to study start and must continue on the stable dose while receiving study treatment; SSA is not considered as a systemic treatment.
  • WHO PS ≤ 1
  • Adequate bone marrow function or organ function

Exclusion Criteria:

  • Previous treatment with any PI3K or AKT inhibitor
  • Discontinuation prior mTOR inhibitor therapy due to toxicity
  • Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma
  • Radiotherapy, or major surgery within 4 weeks prior to study treatment start
  • Hepatic artery embolization or cryoablation/ radiofrequency ablation of hepatic metastasis within 2 months of study treatment start.
  • More than 3 prior systemic treatment regimens (including cytotoxic chemotherapy, targeted therapy, immunotherapy)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: BEZ235 300 mg/400 mg bid (Stage 1)
Stage 1 consisted of a single arm where patients received BEZ235 300mg or 400mg bid. Initially the study started with a dose of 400mg bid. However, following an amendment after the preliminary safety and tolerability data from the first 3 patients treated at the 400mg dose, the dosage was changed to 300mg bid.
Drug: BEZ235 (Stage 1)
The investigational study drug used in this trial was BEZ235, which was supplied as 50mg, 200mg, 300mg, and 400mg solid dispersion sachets. Supply as 200mg and 50mg were provided for dose reduction. Patients were instructed to take the contents of one sachet of BEZ235 twice a day in the morning within 30 minutes after a light meal (breakfast).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
16 weeks after the first BEZ235 administration.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, every 8 weeks up to 31 months
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.
Baseline, every 8 weeks up to 31 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2012

Primary Completion (ACTUAL)

July 1, 2015

Study Completion (ACTUAL)

July 1, 2015

Study Registration Dates

First Submitted

July 6, 2012

First Submitted That Met QC Criteria

August 6, 2012

First Posted (ESTIMATE)

August 7, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

May 2, 2016

Last Update Submitted That Met QC Criteria

April 19, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CBEZ235F2201
  • 2012-000675-16 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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