Advanced neuroendocrine neoplasias G3 (NEN G3) (excluding SCLC and Merkel cell carcinomas) MedDRA version: 20.0 Level: PT Classification code 10057270 Term: Neuroendocrine carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Bavencio 20 mg/ml Konzentrat
Product Name: Avelumab
Product Code: MSB0010718C
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AVELUMAB
Other descriptive nam
Sponsors
University Medical Center of the Johannes Gutenberg-University Mainz
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 18 years - Histologically proven neuroendocrine neoplasia NEN G3 (WHO 2010/2019) - One block or 20 slides (4 microns) of archival tumor tissue to perform central pathological review and biomarker assessment and for translational research - No curative option available - Progression after at least one chemotherapy (platinum based or STZ/TEM/DTIC based chemotherapy) - Presence of measurable disease as per RECIST1.1 criteria - Adequate organ and bone marrow function - ECOG Performance Status 0 – 1 - 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
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 TKI or immune therapy - Neuroendocrine tumors that are potentially curable by surgery - Major surgery within 4 weeks before first dose of study medication. Complete wound healing must be observed at least 10 days prior to enrollment. - Patients who are at increased risk for severe haemorrhage - TACE, TAE, SIRT or PRRT within 8 weeks before first dose of study medication - Patients pretreated with Interferon as last treatment line prior to study entry - Concurrent anticancer treatment - Active infection requiring systemic therapy including, HIV/AIDS, HBV, HCV, Covid 19 - Severe active autoimmune disease that requires immunomodulatory therapy - Uncontrolled hypertension - Congestive heart failure or symptomatic coronary artery disease - Pregnancy or lactation - Vaccination within 4 weeks before the first dose of avelumab and while on trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary study objective is to assess the clinical activity of the combination therapy of Cabozantinib with Avelumab in comparison to monotherapy with avelumab in the AveNEC trial (EudraCT No.: 2016-004373-40) in patients with progressive Neuroendocrine Neoplasias G3 (NEN G3) after standard chemotherapy. The primary end point is the disease control rate (DCR) according to iRECIST after 16 weeks from start of treatment until documented disease progression (PD). The tumor assessment is done every 8 weeks for the first 6 month and every 12 weeks thereafter.;Secondary Objective: Secondary study objectives include the objective response rate (ORR), the duration of disease control (DDC), best overall response (BOR), the progression-free survival time (PFS), the overall survival (OS), the quality of life (QoL) and the safety and tolerability. Exploratory study objectives include correlation of subclassification of the NEN G3 (NET G3 vs NEC) and tumor immune microenvironment (e.g. PD-L1 expression, tumor infiltrating lymphocytes (TIL)) with tumor response and (when tumor tissue on/after treatment is available) effect of treatment on tumor microenvironment. Comparison of the efficacy and tolerability of the combination of Cabozantinib and Avelumab to the monotherapy with avelumab in the AveNEC trial (EudraCT No.: 2016-004373-40) and evaluation of tumor growth rate (TGR).;Primary end point(s): The primary end point is the disease control rate (DCR: CR, PR, SD) according to iRECIST after 16 weeks from start of treatment until documented disease progression (PD).;Timepoint(s) of evaluation of this end point: 16 weeks from start of treatment until disease progression (PD) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Disease control rate (DCR) at week 8, week 24, week 48 - Objective response rate (ORR) - Best overall response (BOR) - Duration of disease control (DDC) - Time to response (TTR) - Progression-free survival time (PFS) - Evaluation of tumor response according to RECIST 1.1 - Overall survival (OS) - Quality of life (QoL) assessed by EORTC QLQ-C30 - Number, severity, and duration of treatment-emergent AEs according to NCI-CTCAE v5.0 - Dose reduction of study drugs - Treatment interruption or termination of study drugs due to adverse events;Timepoint(s) of evaluation of this end point: DCR at week 8, week 24, week 48 ORR, BOR, DDC, TTR, PFS, OS Quality of Life (QoL) assessed by EORTC QLQ-C30 | — |
Countries
Germany
Contacts
Public ContactUniv.-Prof. Dr. med. Matthias Weber
University Medical Center of the Johannes Gutenberg-University Mainz
Outcome results
None listed