BEZ235 Phase II Trial in Patients With Advanced Pancreatic Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.
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.
2 other identifiers
interventional
31
9 countries
17
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Nov 2012
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 6, 2012
CompletedFirst Posted
Study publicly available on registry
August 7, 2012
CompletedStudy Start
First participant enrolled
November 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2015
CompletedResults Posted
Study results publicly available
May 2, 2016
CompletedMay 2, 2016
April 1, 2016
2.7 years
July 6, 2012
March 11, 2016
April 19, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Stage 1 - Progression Free Survival (PFS) Rate Analysis at 16 Weeks as Per Local Radiology Review
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 Outcomes (2)
Stage 1- Overall Response Rate (ORR)
Baseline, every 8 weeks up to 31 months
Stage 1 - Disease Control Rate
Baseline, every 8 weeks up to 31 months
Study Arms (1)
BEZ235 300 mg/400 mg bid (Stage 1)
EXPERIMENTALStage 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.
Interventions
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).
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
Indiana University SC
Indianapolis, Indiana, 46202, United States
Dana Farber Cancer Institute GastrointestionalCancer Clinic
Boston, Massachusetts, 02215, United States
Montefiore Medical Center SC-2
The Bronx, New York, 10467, United States
Ohio State Comprehensive Cancer Center/James Cancer Hospital SC
Columbus, Ohio, 43210, United States
Novartis Investigative Site
Vienna, A-1090, Austria
Novartis Investigative Site
Leuven, 3000, Belgium
Novartis Investigative Site
Lyon, 69437, France
Novartis Investigative Site
Villejuif, 94805, France
Novartis Investigative Site
Essen, 45147, Germany
Novartis Investigative Site
Florence, FI, 50134, Italy
Novartis Investigative Site
Milan, MI, 20133, Italy
Novartis Investigative Site
Milan, MI, 20141, Italy
Novartis Investigative Site
Rotterdam, 3015 CE, Netherlands
Novartis Investigative Site
Barcelona, Catalonia, 08035, Spain
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907, Spain
Novartis Investigative Site
Madrid, Madrid, 28041, Spain
Novartis Investigative Site
Manchester, M20 4BX, United Kingdom
Related Publications (1)
Fazio N, Buzzoni R, Baudin E, Antonuzzo L, Hubner RA, Lahner H, DE Herder WW, Raderer M, Teule A, Capdevila J, Libutti SK, Kulke MH, Shah M, Dey D, Turri S, Aimone P, Massacesi C, Verslype C. A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours. Anticancer Res. 2016 Feb;36(2):713-9.
PMID: 26851029DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Disclosure Office
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 6, 2012
First Posted
August 7, 2012
Study Start
November 1, 2012
Primary Completion
July 1, 2015
Study Completion
July 1, 2015
Last Updated
May 2, 2016
Results First Posted
May 2, 2016
Record last verified: 2016-04