89Zr-bevacizumab PET Imaging in Patients With Neuroendocrine Tumors
Condition: Neuroendocrine Tumors
MeSH terms: Neuroendocrine Tumors
Study type: Observational

Summary: 
      This is a pilot study for evaluation of 89Zr-bevacizumab PET imaging as predictive biomarker
      during treatment with everolimus in patients with neuroendocrine tumors.

      Patients with progressive disease during the last year will receive treatment with everolimus
      10 mg/day orally and 89Zr-bevacizumab PET imaging will be performed before start of treatment
      and after 2 and 12 weeks of treatment in the first three patients. If the scan after 2 weeks
      of treatment is already informative further patients will not undergo a scan at 12 weeks. A
      scan is considered already informative if both scans show at least 30% decrease in uptake in
      case of response, or at least 30% increase in uptake in case of disease progression.

      Four days before the scan patients will be injected intravenously 37 MBq, protein dose 5 mg
      89Zr-bevacizumab. At day 1, day 15 and day 99, PET images will be made for visualization and
      quantification of VEGF in the tumor lesions and blood will be drawn for determination of
      angiogenesis and mTOR pathway related biomarkers.
    

Detailed description: 
      1. Rationale:

           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.

        2. Objectives:

      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
      neuroendocrine tumors.

      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
           with everolimus.

        -  To explore relationships between VEGF pathway related blood biomarkers and changes in
           89Zr-bevacizumab tumor uptake.
    

Intervention name(s): 89Zr-bevacizumab; Everolimus
Intervention type(s): Drug; Drug
Intervention description(s): Intravenous injection 120 MBq; Oral use, 10 mg per day
Other intervention name(s): RAD001
Intervention MeSH terms: Bevacizumab; Everolimus; 89Zr-bevacizumab
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients with metastatic neuroendocrine tumors.
      
Keywords: VEGF imaging; neuroendocrine tumors; biomarker; mTOR inhibition