The study is designed as an open-label, prospective, single arm, multicenter study of everolimus in histologically confirmed, neuroendocrine carcinoma G3 /neuroendocrine tumor G3 after failure of first-line platin-based chemotherapy (open-label pilot study). The aim of this study is to provide a second line therapy to patients with any type of platinum based first line chemotherapy, to gather data on disease control rate and progression free survival.
As more efficient drugs are urgently needed for the treatment of neuroendocrine tumors the investigator evaluated phosphorylated Mammalian target of rapamycin (mTOR) and effectors in a series of NEC G3 at the Charité Center. Everolimus showed antiproliferative effects in bronchial NET. In a second approach the data of this study should be the basis to generate another study to further explore everolimus as maintenance therapy in NEC G3/ NET G3.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Formulation: 10 mg/day Route: oral (tablet)
Charité-Universitätsmedizin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum
Berlin, Germany
Incidence of adverse events (AEs)
Incidence of adverse events (AEs) overall and by severity, and serious adverse events (SAEs). Severity will be assessed using the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) for Adverse Events, version 4.03 (CTCAEv4.03). To evaluate tolerability and safety of everolimus in second-line treatment of poorly differentiated neuroendocrine carcinoma / neuroendocrine carcinoma G3 according to WHO 2010 and neuroendocrine tumors G3.
Time frame: approx. 18 month
Progression free survival (PFS)
Progression free survival (PFS) as the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse as per local radiology assessment using Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)
Time frame: approx. 18 month
Objective response rate (ORR)
Objective response rate defined as the rate of best overall response (CR+PR), determined by RECIST V 1.1.
Time frame: approx. 18 month
Disease control rate (DCR)
Disease control rate defined as the rate of best overall response and stable disease (CR+PR+SD), determined by RECIST V 1.1.
Time frame: approx. 18 month
Duration of response (DR)
Duration of response is defined as the time from onset of the first objective tumor response (CR/PR) to objective tumor progression or death from any cause.
Time frame: approx. 18 month
Overall Survival (OS)
OS is defined as the time from date of randomization to the date of death from any cause. If a patient is not known to have died at the date of analysis cut-off, the OS will be censored at the last date of contact.
Time frame: approx. 18 month
Quality of life
Quality of life (HRQoL) will be evaluated using the European Organisation for Research and Treatment of Cancer (EORTC), to assess the quality of life of cancer patients questionnaire (QLQ-C30)
Time frame: approx. 18 month
chromogranin A & B
Percentage of patients showing normalization or a decrease of chromogranin A \& B
Time frame: approx. 12 month
Time to Progression (TTP)
Time to progression (TTP) is the time from date of start of treatment to the date of event defined as the first documented progression due to underlying cancer.
Time frame: approx. 18 month
neuron-specific enolase
Percentage of patients showing normalization or a decrease of neuron-specific enolase
Time frame: approx. 12 month
progastrin releasing peptide
Percentage of patients showing normalization or a decrease of progastrin releasing peptide.
Time frame: approx. 12 month
Correlation mTOR pathway components in tumor tissue to tumor response
To explore expression of mTOR pathway components in tumor tissue (archive) in correlation to tumor response
Time frame: approx. 18 month
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