A Biological Prospective Study in Patients With Metastatic Pancreatic NETs Treated With Everolimus
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.
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
|Eligible Ages||18 Years and Over|
Inclusion Criteria:1. Histological diagnosis of metastatic well/moderately differentiated pancreatic neuroendocrine tumor 2. Patient incoming to be treated with everolimus outside clinical trials or within a clinical trial that permits the concurrent inclusion in an ancillary trial 3. Written informed consent must be signed and dated by the patient and the investigator prior to inclusion.
Exclusion Criteria:1. Patients with poorly differentiated neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid, small cell carcinoma, Merkel cell carcinoma. 2. Patients with pancreatic NETs not eligible to be treated with everolimus 3. Patients with ongoing everolimus treatment 4. Prior therapy with mTOR inhibitors
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 0: Exploratory study involving very limited human exposure to the drug to determine whether a drug is modulating its target.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|European Institute of Oncology|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
The disease, disorder, syndrome, illness, or injury that is being studied.
|Pancreatic Neuroendocrine Tumour Metastatic|
• 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.
- - Material and Methods : 1.
- - Subtype 2 somatostatin receptor, - Phospho-AKT - Phospho-mTOR - Phospho-4E-BP1 - Phospho-p70-S6 kinase Rabbit anti-tuberous sclerosis complex 2 (TSC2) Cell Signaling Technology - Mouse anti-PTEN Cell Signaling Technology 3.
- - Study design Baseline, after 1 month of therapy, after three months of therapy and at progression: - Abdomen DWI-MRI - CEC, CEPs - Circulating VEGF, VEGFR-2, bFGF, TSP-1 Baseline biopsy of a metastatic site and possibly a new biopsy at the time of tumor progression Correlation of biological parameters with clinical outcome ( tumor response and progression free survival, Response Evaluation Criteria in Solid Tumors , RECIST 1.0 criteria) • Statistical analysis: This is an exploratory study on the potential predictive value of some biological factors (CECs, VEGF and bFGF among them) expressed in terms of reducing risk of progression in patients with advanced pancreatic NETs treated with Everolimus.
- - ≥ 2.2/uL vs.#46;< 2.2/uL for CEC at basal or - ≤ 65.6 vs.#46;> 65.6 for FGF levels after two months since start treatment or - ≤ 32.5 vs.#46;> 32.5 for VEGF levels after two months since start treatment The sample size is calculated to compensate for the power loss of the log-rank test assuming an average and uniform log-rank test drop-out of 10% and bearing in mind that the threshold values refer to the 25th, 75th and 50th percentile distributions of CEC, bFGF, and VEGF, respectively.
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European Institute of Oncology
Nicola Fazio, MD,PhD