89Zr-bevacizumab PET Imaging as Predictive Biomarker for Everolimus Efficacy in Patients With Neuroendocrine Tumors
18 Years
80 Years
Both
Neuroendocrine Tumors
Trial Information
89Zr-bevacizumab PET Imaging as Predictive Biomarker for Everolimus Efficacy in Patients With Neuroendocrine Tumors
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.
Inclusion Criteria:
- adult patients with metastatic neuroendocrine tumors
- radiological documentation of progressive disease over the past year
- measurable disease according to RECIST criteria
- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x
109/L, Hb > 9 g/dL.
- Adequate liver function: serum bilirubin: ≤ 1.5 x ULN, ALT and AST ≤ 2.5x ULN.
Patients with known liver metastases: AST and ALT ≤ 5x ULN.
- Adequate renal function: serum creatinine ≤ 1.5 x ULN.
- Fasting serum cholesterol ≤300 mg/dL OR 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x
ULN. NOTE: In cases where one or both of these thresholds are exceeded, the patient
can only be included after initiation of appropriate lipid lowering medication
Exclusion Criteria:
- uncontrolled medical conditions (eg, unstable angina, symptomatic heart failure,
serious intercurrent infections)
- any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule of the study
- Patients with uncontrolled diabetes mellitus as defined by fast blood sugar > 1.5 x
ULN.
- Prior therapy with RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus).
- Concomitant medications known to inhibit, induce or be a substrate to isoenzyme CYP3A
are excluded unless the drugs are medically necessary and no substitutes are
available. If there are no acceptable substitutes, special precautions should be
taken in these patients
Type of Study:
Observational
Study Design:
Observational Model: Cohort, Time Perspective: Prospective
Outcome Measure:
change in 89Zr-bevacizumab uptake
Outcome Description:
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.
Outcome Time Frame:
12 weeks
Safety Issue:
No
Principal Investigator
Elisabeth GE de Vries, MD, PHD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University Medical Centre Groningen
Authority:
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Study ID:
20091104
NCT ID:
NCT01338090
Start Date:
April 2010
Completion Date:
March 2012
Related Keywords:
- Neuroendocrine Tumors
- VEGF imaging
- neuroendocrine tumors
- biomarker
- mTOR inhibition
- Neuroendocrine Tumors
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