Clinical Trial: A Biological Prospective Study in Patients With Metastatic Pancreatic NETs Treated With Everolimus
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: An Angiogenic Study in Patients With Well/Moderately Differentiated Metastatic Pancreatic Neuroendocrine Tumors Treated With Everolimus
Brief Summary: Everolimus represents an approved therapy for patients with advanced well/moderately differentiated pancreatic NETs. Although some patients could benefit from this drug in terms of long-term tumor growth control, others are resistant upfront or become resistant during treatment. Therefore, it is crucial to detect some biological factors which can help to identify the responsive tumors. Given that Everolimus is a biological agent and its mechanism of action can be partially directed towards angiogenesis its effects can be studied on different levels and with different methods. Upfront and early surrogate predictive markers of activity/efficacy can be studied on tumor tissue, tumor imaging, and peripheral blood. mTOR pathways alterations, circulating endothelial cells, and other circulating angoigenic factors will be correlated with clinical outcome. Tumor perfusion and circulating markers will be studied also as markers of response compared with the morphological imaging.
Detailed Summary:
• Background:: Everolimus has been reported to be effective compared with placebo in well/moderately differentiated pancreatic NETs in terms of progression-free survival (PFS) improvement. However, a number of patients are refractory upfront or become resistant after few months of therapy. Therefore, it is crucial to detect some biological factors which can help to identify the responsive tumors. Everolimus is a biological agent and its mechanism of action can be partially directed towards angiogenesis. This can be studied on different levels and with different methods. Upfront and early surrogate predictive markers of activity/efficacy can be studied on tumor tissue, on tumor imaging, and on the peripheral blood. Tumor study with diffusion-MRI and angiogenic circulating markers can be studied also as markers of response compared with the morphological imaging.
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Material and Methods :
- Circulating Endothelial Cells (CECs) and Circulating endothelial progenitors (CEPs) will be performed by flow cytometry. The monoclonal antibodies used for the search of CECs and CEPs include: cluster of differentiation antigen 45 (CD45), CD31, CD133, CD146, CD34, VEGFR-2, 7-amino-actinomycin D (7-AAD) and Syto1. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), VEGFR-2 and thrombospondin-1 (TSP-1) will be also detected on the peripheral blood.
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On the tumor tissue the following determinations will be performed, including:
- Subtype 2 somatostatin receptor,
- Phospho-AKT
- P
Sponsor: European Institute of Oncology
Current Primary Outcome: Circulating angiogenic factors, molecular imaging and tumor tissue factors changes during treatment with RAD001 at baseline, week 4, week 12 and at disease progression. [ Time Frame: Baseline, week 4, week 12 up to tumor progression ]
Angiogenic factors (circulating endothelial cells, CECs; serum VEGF, bFGF, VEGFR-2, TSP-1) determined by serum samples; tumor tissue mTOR pathway alterations determined by Immunohistochemical staining ; ADC (apparent diffusion coefficient) calculated by Magnetic Resonance Imaging (MRI)
Original Primary Outcome: Same as current
Current Secondary Outcome:
- OS (overall survival) [ Time Frame: Baseline to death ]
- RR (response rate) , including SD (stable disease) and PR (partial response) [ Time Frame: Baseline to best tumor response or unacceptable toxicity ]
- TTP, time to progression [ Time Frame: Baseline to tumor progression or unacceptable toxicity ]
Original Secondary Outcome: Same as current
Information By: European Institute of Oncology
Dates:
Date Received: June 17, 2014
Date Started: September 2013
Date Completion: December 2017
Last Updated: August 9, 2016
Last Verified: August 2016
