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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01658436
First received: July 6, 2012
Last updated: April 19, 2016
Last verified: April 2016

July 6, 2012
April 19, 2016
November 2012
July 2015   (final data collection date for primary outcome measure)
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. ] [ Designated as safety issue: No ]
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.
  • Stage 1 - Progression Free Survival (PFS) at 16 weeks [ Time Frame: 16 weeks after the first BEZ235 administration. ] [ Designated as safety issue: No ]
    Stage 1 Progression Free Survival is defined as the number of progression free patients divided by the total number of patients in the full analysis set. PFS will be assessed according to local radiological assessment per modified RECIST v1.1
  • Stage 2 - Progression Free Survival (PFS) [ Time Frame: from the randomization date until the date of first documented progression or date of death from any cause which ever come first, assessed up to 30 months. ] [ Designated as safety issue: No ]
    Stage 2 Progression Free Survival is defined as the time from the randomization date until objective tumor progression or death from any cause. PFS will be assessed according to local radiological assessment per modified RECIST v1.1
Complete list of historical versions of study NCT01658436 on ClinicalTrials.gov Archive Site
  • Stage 1- Overall Response Rate (ORR) [ Time Frame: Baseline, every 8 weeks up to 31 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.
  • Stage1&2 - Frequency and severity of Adverse Events (AEs) [ Time Frame: three times per month during first month of therapy, then twice a month and 30 days after study treatment termination. ] [ Designated as safety issue: No ]
    Measure the safety and tolerability of BEZ235 therapy by monitoring the concomitant medications, abnormal laboratory values, physical examination and other safety data as appropriate.
  • Stage 1&2- Evaluate Overall Response Rate [ Time Frame: Baseline, every 8 weeks. ] [ Designated as safety issue: No ]
    Overall Response rate is 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.
  • Stage 1&2- Disease Control rate [ Time Frame: Baseline, every 8 weeks ] [ Designated as safety issue: No ]
    Disease control rate is 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.
  • Stage 1&2- Measure Duration of Response [ Time Frame: Baseline, evry 8 weeks. ] [ Designated as safety issue: No ]
    Duration of overall response is defined only for the responder subset: patients with confirmed complete response or partial response based on investigator's assessment. It is the elapsed time between the date of first documented response and the following date of event defined as the first documented progression or death due to underlying cancer, per RECIST version 1.1..
  • Stage 2- Overall survival [ Time Frame: up to approximately 28 months ] [ Designated as safety issue: No ]
    Time from randomisation to the date of death due to any cause.
Not Provided
Not Provided
 
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.

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.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Pancreatic Neuroendocrine Tumors (pNET)
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).
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.
Intervention: Drug: BEZ235 (Stage 1)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
31
July 2015
July 2015   (final data collection date for primary outcome measure)

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)
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Austria,   Belgium,   France,   Germany,   Italy,   Netherlands,   Spain,   United Kingdom
Poland,   Thailand,   Turkey
 
NCT01658436
CBEZ235F2201, 2012-000675-16
Yes
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP