Trial Information

89Zr-bevacizumab PET Imaging in Patients With Renal Cell Carcinoma Treated With Everolimus; a Pilot Study

Background of the study

The majority of renal cell carcinomas (RCC) is characterized by profound angiogenesis
because of inactivation of the Von Hippel Lindau gene. Angiogenesis inhibitors are
established first line treatment options in the metastatic setting. Patients with
progressive disease during or after treatment with angiogenesis inhibitors can benefit from
treatment with everolimus, an oral mTOR inhibitor that resulted in doubling of progression
free survival in a phase III study. Currently it is not possible to predict which patient
will benefit from treatment with mTOR inhibitors. A predictive biomarker for efficacy of
mTOR inhibitors is urgently needed as it may spare the patients unnecessary side effects,
safes costs for the society as mTOR inhibitors are are very expensive agents, and may speed
up research on new drugs, drug combinations and drug dosing. One of the actions of mTOR
inhibitors is blockage of production of vascular endothelial growth factor (VEGF), and this
is thought to be the primary mechanism that is responsible for antitumor activity in RCC.
The investigators hypothesize that non-invasive measurement of VEGF in the tumour and its
surroundings by 89Zr-bevacizumab PET imaging before and shortly after start of everolimus is
a good readout of efficacy of everolimus in patients with RCC.

Objective of the study

The primary objective of the study is to evaluate the feasibility of 89Zr-bevacizumab PET
imaging as a biomarker before and during treatment with everolimus in patients with
metastatic RCC. 89Zr-bevacizumab PET imaging will be regarded a promising biomarker if
uptake changes after institution of treatment.

Study design

This is a pilot study for evaluation of 89Zr-bevacizumab PET imaging as a biomarker during
treatment with everolimus in patients with mRCC.

89Zr-bevacizumab PET imaging will be performed before start of treatment and after 2 and 6
weeks of treatment.

Study population

14 patients who will start treatment with everolimus for metastatic RCC will be included in
this study.

Primary study parameters

The primary endpoint is change in 89Zr-bevacizumab uptake in tumor lesions between the
baseline scan and the scan during treatment.

Secondary study parameters The secondary endpoint is progressive disease according to
Response Evaluation Criteria in Solid Tumors (RECIST) criteria, after 3 months 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.

Nature and extent of the burden and risks associated with participation, benefit and group
relatedness

Patients will be intravenously injected at 3 time points with 37MBq resulting in a
cumulative radiation dose of 54 mSv. According to ICRP 62 this radiation dose falls in
category III (moderate risk).

Life expectancy of the patients is limited because of their incurable renal cell carcinoma,
making the risk of development of a secondary malignancy clinically likely not relevant.

Patients have to pay 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-bevacizumab 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.