Advanced Pancreatic Neuroendocrine Tumors (pNET) Clinical Trial
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.
| Verified date | October 2015 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 31 |
| Est. completion date | July 2015 |
| Est. primary completion date | July 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Austria | Novartis Investigative Site | Wien | |
| Belgium | Novartis Investigative Site | Leuven | |
| France | Novartis Investigative Site | Lyon | |
| France | Novartis Investigative Site | Villejuif Cedex | |
| Germany | Novartis Investigative Site | Essen | |
| Italy | Novartis Investigative Site | Firenze | FI |
| Italy | Novartis Investigative Site | Milano | MI |
| Italy | Novartis Investigative Site | Milano | MI |
| Netherlands | Novartis Investigative Site | Rotterdam | |
| Spain | Novartis Investigative Site | Barcelona | Catalunya |
| Spain | Novartis Investigative Site | Hospitalet de LLobregat | Catalunya |
| Spain | Novartis Investigative Site | Madrid | |
| United Kingdom | Novartis Investigative Site | Manchester | |
| United States | Dana Farber Cancer Institute GastrointestionalCancer Clinic | Boston | Massachusetts |
| United States | Montefiore Medical Center SC-2 | Bronx | New York |
| United States | Ohio State Comprehensive Cancer Center/James Cancer Hospital SC | Columbus | Ohio |
| United States | Indiana University SC | Indianapolis | Indiana |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Austria, Belgium, France, Germany, Italy, Netherlands, Spain, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Stage 1 - Progression Free Survival (PFS) at 16 weeks | 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 | 16 weeks after the first BEZ235 administration. | No |
| Primary | Stage 2 - Progression Free Survival (PFS) | 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 | 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. | No |
| Secondary | Stage1&2 - Frequency and severity of Adverse Events (AEs) | Measure the safety and tolerability of BEZ235 therapy by monitoring the concomitant medications, abnormal laboratory values, physical examination and other safety data as appropriate. | three times per month during first month of therapy, then twice a month and 30 days after study treatment termination. | No |
| Secondary | Stage 1&2- Evaluate Overall Response Rate | 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. | Baseline, every 8 weeks. | No |
| Secondary | Stage 1&2- Disease Control rate | 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. | Baseline, every 8 weeks | No |
| Secondary | Stage 1&2- Measure Duration of Response | 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.. | Baseline, evry 8 weeks. | No |
| Secondary | Stage 2- Overall survival | Time from randomisation to the date of death due to any cause. | up to approximately 28 months | No |