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.

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Key information

Conditions

Pancreatic Neuroendocrine Tumors (pNET) Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors Neuroectodermal Tumors, Primitive

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Vienna, Austria

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

BEZ235 (Stage 1)

Drug

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 outcomes

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 outcomes

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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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.

Important dates

Study start: 2012
Primary completion: 2015
Study completion: 2015
First posted: Aug 7, 2012
Registry last updated: May 2, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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