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
  Purpose

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 Intervention Phase
Pancreatic Neuroendocrine Tumors (pNET)
Drug: BEZ235 (Stage 1)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 31
Study Start Date: November 2012
Study Completion Date: July 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01658436

Locations
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
Austria
Novartis Investigative Site
Wien, Austria, A-1090
Belgium
Novartis Investigative Site
Leuven, Belgium, 3000
France
Novartis Investigative Site
Lyon, France, 69437
Novartis Investigative Site
Villejuif Cedex, France, 94805
Germany
Novartis Investigative Site
Essen, Germany, 45147
Italy
Novartis Investigative Site
Firenze, FI, Italy, 50134
Novartis Investigative Site
Milano, MI, Italy, 20141
Novartis Investigative Site
Milano, MI, Italy, 20133
Netherlands
Novartis Investigative Site
Rotterdam, Netherlands, 3015 CE
Spain
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
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01658436     History of Changes
Other Study ID Numbers: CBEZ235F2201  2012-000675-16 
Study First Received: July 6, 2012
Results First Received: March 11, 2016
Last Updated: April 19, 2016
Health Authority: United States: Food and Drug Administration
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
France: ANSM
Germany: BfarM
Italy: AIFA
Netherlands: Dutch Healthcare Authority (NZA)
Spain: Spanish Agency of Medicines (AEMPS)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
advanced pancreatic neuroendocrine tumor
BEZ235
pNET

Additional relevant MeSH terms:
Neuroendocrine Tumors
Carcinoid Tumor
Adenoma, Islet Cell
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Adenoma
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on July 28, 2016