BEZ235 Phase II Trial In Patients With Advanced Pancreatic Neuroendocrine Tumors (pNET) After Failure Of MTOR Inhibitor Therapy.

Study Overview

BEZ235 Phase II Trial in 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.

N/A

Pancreatic Neuroendocrine Tumors (pNET)

DRUG: BEZ235 (Stage 1)

CBEZ235F2201
2012-000675-16 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2012-07-06	Results First Submitted 2016-03-11	Last Update Submitted that met QC Criteria 2016-04-19
First Submitted that Met QC Criteria 2012-08-06	Results First Submitted that Met QC Criteria 2016-04-19	Last Update Posted (ESTIMATED) 2016-05-02
First Posted (ESTIMATED) 2012-08-07	Results First Posted 2016-05-02	Last Verified 2016-04

Study Plan

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

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	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 sac

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

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 sac

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Stage 1- Overall Response Rate (ORR)	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	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

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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)

Collaborators and Investigators

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

Investigators

STUDY_DIRECTOR: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications

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

General Publications

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.

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Clinical Trial Record