To evaluate the feasibility of 89Zr-bevacizumab-PET imaging as predictive biomarker before and during treatment with everolimus in patients with neuroendocrine tumors.
ID
Source
Brief title
Condition
- Endocrine neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is 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.
Secondary outcome
The secondary endpoint is progressive disease according to Response Evaluation
Criteria in Solid Tumors (RECIST) criteria on CT after 12 weeks of treatment.
Progression is defined as the appearance of new disease or an increase of 20%
in the sum of the longest diameters of the target lesions.
Background summary
Profound angiogenesis is an important characteristic of neuroendocrine tumors.
Antiangiogenic drugs including sunitinib, bevacizumab and everolimus have shown
antitumor activity in neuroendocrine tumors. We participated in the RAD001
studies for neuroendocrine tumors. From preclinical studies including studies
performed in our own lab we 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 we have eveloped 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 we have already proven for a VEGF-receptor tyrosine kinase
inhibitor. Currently this tracer is used in clinical trials. We would like to
investigate whether all neuroendocrine tumors produce VEGF and whether they
differ in their response to inhibition of VEGF by mTOR.
Study objective
To evaluate the feasibility of 89Zr-bevacizumab-PET imaging as predictive
biomarker before and during treatment with everolimus in patients with
neuroendocrine tumors.
Study design
This is a pilot study for evaluation of 89Zr-bevacizumab PET imaging as
predictive biomarker during treatment with everolimus in patients with
neuroendocrine tumors.
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.
Study burden and risks
The first 3 patients will be intravenously injected at 3 times points with 37
MBq, subsequent patients will recieve 2 or 3 injections with 37 MBq
89Zr-becizumab. This results in a cumulative radiation dose of 54 mSv
respectively 36 mSv. Some patients will have their scnas with a PET/CT camera,
this results in an additional radiation dose of 1.5 mSV pers can (total dose
58.5 mSv for 3 scanas and 39 mSv for 2 scans). According to ICRP 62 this
radiation dose falls in category III (moderate risk).
Patients have to pay 2 or 3 extra visits to the hospital for tracer injection.
PET scans will be performed on regular visit days. Blood samples for biomarkers
will be drawn during routine blood investigations. There is no direct benefit
for the patients in this study. If 89Zr-bevcizumab PET imaging however is a
predictive biomarker for angiogenesis inhibitors, many patients can be spared
unnecessary side effects and society can be spared costs of futile treatment in
the future.
Hanzeplein 1
9713 GZ Groningen
NL
Hanzeplein 1
9713 GZ Groningen
NL
Listed location countries
Age
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, uncontrolled diabetes)
• any psychological, familial, sociological condition potentially hampering compliance with the study protocol and follow-up schedule of the study
• Prior therapy with RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-017195-24-NL |
| CCMO | NL30950.042.09 |