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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01658436
Recruitment Status : Completed
First Posted : August 7, 2012
Results First Posted : May 2, 2016
Last Update Posted : May 2, 2016
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Pancreatic Neuroendocrine Tumors (pNET) Drug: BEZ235 (Stage 1) Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.
Study Start Date : November 2012
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

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).

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

Information from the National Library of Medicine

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

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)

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 identifier (NCT number): NCT01658436

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

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals Identifier: NCT01658436    
Other Study ID Numbers: CBEZ235F2201
2012-000675-16 ( EudraCT Number )
First Posted: August 7, 2012    Key Record Dates
Results First Posted: May 2, 2016
Last Update Posted: May 2, 2016
Last Verified: April 2016
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
advanced pancreatic neuroendocrine tumor
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Adenoma, Islet Cell
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Glandular and Epithelial
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents