89Zr-bevacizumab PET Imaging as Predictive Biomarker for Everolimus Efficacy in Patients With Neuroendocrine Tumors
Profound angiogenesis is an important characteristic of neuroendocrine tumors.
Antiangiogenic drugs including sunitinib, bevacizumab and everolimus have shown
antitumor activity in neuroendocrine tumors. The investigators participated in the
RAD001 studies for neuroendocrine tumors. From preclinical studies including studies
performed in our own lab the investigators know that everolimus downregulates VEGF.
Currently it is not possible to predict which individual patient will benefit from
treatment with an mTOR inhibitor. A predictive biomarker for efficacy of mTOR
inhibitors is urgently needed and would be helpful, as a predictive biomarker may
facilitate the development of combination therapies, of individual titration of the
dose, and it may facilitate early clinical studies. Furthermore, it may spare the
patients unnecessary side effects. mTOR inhibitors may fail in individual patients
because angiogenesis is not sufficiently inhibited. Non-invasive imaging of VEGF before
and early after start of treatment may have predictive value for treatment efficacy.
Within the UMCG the investigators have an active ongoing research line on molecular
imaging. The investigators have developed as part of this the 89Zr-bevacizumab PET
label for non-invasive measurement of VEGF levels in the tumor and its surrounding
microenvironment. This tracer can give insight in the tumors' dependency on
angiogenesis as the investigators have already proven for a VEGF-receptor tyrosine
kinase inhibitor. Currently this tracer is used in clinical trials. The investigators
would like to examine whether all neuroendocrine tumors produce VEGF and whether they
differ in their response to inhibition of VEGF by mTOR.
The primary objective is to evaluate the feasibility of 89Zr-bevacizumab-PET imaging as
predictive biomarker before and during treatment with everolimus in patients with
The secondary Objectives are the following:
- To explore if 89Zr-bevacizumab PET imaging can differentiate patients with progressive
neuroendocrine tumors from patients with non-progressive disease early during treatment
- To explore relationships between VEGF pathway related blood biomarkers and changes in
89Zr-bevacizumab tumor uptake.
Observational Model: Cohort, Time Perspective: Prospective
change in 89Zr-bevacizumab uptake
The change in 89Zr-bevacizumab uptake in tumor lesions between the baseline PET scan and the scans performed after 2 and 12 weeks of everolimus treatment in patients with neuroendocrine tumors. In addition, effect sizes and confidence intervals will be determined.
Elisabeth GE de Vries, MD, PHD
University Medical Centre Groningen
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)