Safety and Tolerability of Everolimus as Second-line Treatment in Poorly Differentiated Neuroendocrine Carcinoma / Neuroendocrine Carcinoma G3 (WHO 2010) and Neuroendocrine Tumor G3 - an Investigator Initiated Phase II Study (EVINEC)
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|ClinicalTrials.gov Identifier: NCT02113800|
Recruitment Status : Recruiting
First Posted : April 15, 2014
Last Update Posted : January 23, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Poorly Differentiated Malignant Neuroendocrine Carcinoma Neuroendocrine Carcinoma, Grade 3 Neuroendocrine Carcinoma, Grade 1 [Well-differentiated Neuroendocrine Carcinoma] That Switched to G3 Neuroendocrine Carcinoma, Grade 2 [Moderately Differentiated Neuroendocrine Carcinoma] That Switched to G3 Neuroendocrine Tumor, Grade 3 and Disease Progression as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)||Drug: Everolimus (Afinitor®)||Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety and Tolerability of Everolimus as Second-line Treatment in Poorly Differentiated Neuroendocrine Carcinoma / Neuroendocrine Carcinoma G3 (WHO 2010) and Neuroendocrine Tumor G3 - an Investigator Initiated Phase II Study|
|Study Start Date :||August 2015|
|Estimated Primary Completion Date :||November 2018|
|Estimated Study Completion Date :||February 2019|
Experimental: Single Arm
Patients receive Everolimus orally, 10 mg/day.
The end of study will be performed when tumor progression has been observed for 28 patients. Patients who are still under treatment at that time may continue with chemotherapy at the discretion of the investigator, but will be excluded from the study.
Drug: Everolimus (Afinitor®)
Formulation: 10 mg/day Route: oral (tablet)
- Incidence of adverse events (AEs) [ Time Frame: approx. 18 month ]
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.
- Progression free survival (PFS) [ Time Frame: approx. 18 month ]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.)
- Objective response rate (ORR) [ Time Frame: approx. 18 month ]Objective response rate defined as the rate of best overall response (CR+PR), determined by RECIST V 1.1.
- Disease control rate (DCR) [ Time Frame: approx. 18 month ]Disease control rate defined as the rate of best overall response and stable disease (CR+PR+SD), determined by RECIST V 1.1.
- Duration of response (DR) [ Time Frame: approx. 18 month ]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.
- Overall Survival (OS) [ Time Frame: approx. 18 month ]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.
- Quality of life [ Time Frame: approx. 18 month ]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)
- chromogranin A & B [ Time Frame: approx. 12 month ]Percentage of patients showing normalization or a decrease of chromogranin A & B
- Time to Progression (TTP) [ Time Frame: approx. 18 month ]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.
- neuron-specific enolase [ Time Frame: approx. 12 month ]Percentage of patients showing normalization or a decrease of neuron-specific enolase
- progastrin releasing peptide [ Time Frame: approx. 12 month ]Percentage of patients showing normalization or a decrease of progastrin releasing peptide.
- Correlation mTOR pathway components in tumor tissue to tumor response [ Time Frame: approx. 18 month ]To explore expression of mTOR pathway components in tumor tissue (archive) in correlation to tumor response
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02113800
|Contact: Katrin Krause, B.Sc.||+49 30 8145 344 ext 32||Katrin.Krause@aio-studien-ggmbh.de|
|Charité-Universitätsmedizin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum||Recruiting|
|Berlin, Germany, 13353|
|Contact: Marianne Pavel, Prof. Dr. firstname.lastname@example.org|
|Principal Investigator: Marianne Pavel, Prof. Dr.|
|Principal Investigator:||Marianne Pavel, Prof. Dr.||Charité-Universitätsmedizin|