Clinical trial NCT01658436: BEZ235 Phase II Trial in Patients With Advanced Pancreatic Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Neuroendocrine Tumors (pNET)
Keywords: advanced pancreatic neuroendocrine tumor
BEZ235
pNET
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-08-07
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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)

Primary outcomes:
measure: Stage 1 - Progression Free Survival (PFS) Rate Analysis at 16 Weeks as Per Local Radiology Review
timeFrame: 16 weeks after the first BEZ235 administration.
Secondary outcomes:
measure: Stage 1- Overall Response Rate (ORR)
timeFrame: Baseline, every 8 weeks up to 31 months
measure: Stage 1 - Disease Control Rate
timeFrame: Baseline, every 8 weeks up to 31 months
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University SC
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute GastrointestionalCancer Clinic
state: Massachusetts
city: Bronx
country: United States
facility: Montefiore Medical Center SC-2
state: New York
city: Columbus
country: United States
facility: Ohio State Comprehensive Cancer Center/James Cancer Hospital SC
state: Ohio
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.