advanced, metastatic high grade neuroendocrine carcinomas NEC G3 (WHO 2010)
Conditions
Interventions
Trade Name: Bavencio
Product Name: Avelumab
Product Code: MSB0010718C
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AVELUMAB
Other descriptive name: Bavencio
Concentr
Sponsors
University Medical Center of the Johannes Gutenberg-University Mainz
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female patient = 18 years - Histologically proven neuroendocrine neoplasia NEC G3 (WHO 2010) - One block or 20 slides (4 microns) of archival tumor tissue to perform central pathological review and biomarker assessment - No curative option available - Progressive disease within 9 months before study initiation and after prior at least one chemotherapy (platinum based chemotherapy or STZ/TEM/DTIC based chemotherapy in NET G3) - Presence of measurable disease as per RECIST1.1 criteria - ECOG Performance Status 0 – 2 - Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: - Merkel Cell carcinoma (MCC) or small cell lung cancer (SCLC) - Typical or Atypical Carcinoid of the lung with a Ki67 < 20% - Prior therapy with any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) - Neuroendocrine tumors that are potentially curable by surgery - Major surgery within 4 weeks of first dose of study medication. - TACE, TAE, SIRT or PRRT within 3 months of starting study treatment - Patients pretreated with Interferon as last treatment line prior to study entry - Concurrent anticancer treatment - active infection requiring systemic therapy including, HIV/AIDS, HBV or HCV - Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent - Pregnancy or lactation - Vaccination within 4 weeks of the first dose of avelumab and while on trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the clinical activity of avelumab as determined by the disease control rate (DCR) according to RECIST1.1 from start of study drug until documented disease progression (PD), assessed every 8 weeks for the first 6 month and every 12 weeks thereafter.;Secondary Objective: To assess disease control rate (DCR) on other assessments To assess the objective response rate (ORR) To assess the best overall response (BOR) To assess the duration of disease control. To assess the progression-free survival time (PFS). To assess the overall survival (OS). To assess the time to response (TTR) To assess the quality of life (QoL). To evaluate the safety and tolerability. Exploratory objectives include assessment of subclassification of the NEC according to histomorphological differentiation and proliferation rate Ki67 (20-55 % vs. > 55%), changes from baseline in Chromogranin A (CgA) and Neuron specific enolase (NSE) levels, and evaluation of PD-L1 expression and the potential association of these factors with response rate, evaluation of tumor growth rate (TGR), and evaluation of Tumor response according to irRECIST.;Primary end point(s): The primary endpoint is the disease control rate (CR, PR, SD according to RECIST1.1) after 16 weeks of study treatment;Timepoint(s) of evaluation of this end point: after 16 weeks of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are: - Disease control rate (DCR) on other assessments - Objective response rate (ORR) on every assessment according to RECIST1.1 - Best overall response (BOR) according to RECIST1.1 - Duration of disease control and time to response (TTR) according to RECIST1.1 - Median Progression-free survival time (PFS) - Overall survival (OS) and survival rate after 1 and 2 years - Quality of life (QoL) assessed by EORTC QLQ-C30 on every assessment - Number, severity, and duration of treatment-related AEs according to NCICTCAE v4.0 The exploratory efficacy endpoints are: - histomorphological subclassification into NET G3 (differentiated morphology, ki67 20-55%) versus NEC G3 (small cell or large cell undifferentiated morphology and/or Ki67 > 55%) - Chromogranin A (CgA) and Neuron specific enolase (NSE) serum levels - PD-L1 expression measured by IHC or other established techniques - Tumor growth rate (TGR) - Disease control rate (DCR) according irRECIST ;Timepoint(s) of evaluation of this end point: DCR, ORR: on every assessment BOR: after 16, 24 weeks and 1 year TTR: after 1 year PFS: after 1 year OS and survival rate: after 1 and 2 year QoL: assessed on every assessment | — |
Countries
Germany
Contacts
Public ContactUniv.-Prof. Dr. med. M. M. Weber
University Medical Center of the Johannes Gutenberg-University Mainz
Outcome results
None listed