Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01658436
First received: July 6, 2012
Last updated: October 29, 2014
Last verified: October 2014
  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.


Condition Intervention Phase
Advanced Pancreatic Neuroendocrine Tumors (pNET)
Drug: BEZ235
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
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) 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


Secondary Outcome Measures:
  • 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.


Enrollment: 31
Study Start Date: November 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BEZ235
The investigational study drug to be used in this trial is BEZ235, which is supplied as 300mg, 200mg and 50mg sachets. Supply as 200mg and 50mg are provided for dose reduction. Patients should be instructed to take the contents of one sachets of BEZ235 twice a day in the morning within 30 minutes after a light meal (breakfast).On stage 1-open label-30 patients will receive BEZ235 . On stage 2-double-blind setting with 99 patients additional patients-only patients randomized under BEZ arm will be treated with study medication.
Drug: BEZ235
Placebo Comparator: Placebo
Matching Placebo for stage 2.
Drug: BEZ235

  Eligibility

Ages Eligible for Study:   18 Years and older
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)

Other protocol defined inclusion/exclusion criteria may apply.

  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 SC
Boston, Massachusetts, United States, 02115
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, 20133
Novartis Investigative Site
Milano, MI, Italy, 20141
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
London, United Kingdom, W12 0HS
Novartis Investigative Site
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01658436     History of Changes
Other Study ID Numbers: CBEZ235F2201, 2012-000675-16
Study First Received: July 6, 2012
Last Updated: October 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
pancreatic
neuroendocrine tumor

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

ClinicalTrials.gov processed this record on November 25, 2014