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…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms benign
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is change in 89Zr-bevacizumab uptake in tumor lesions
between the baseline scan and the scan during treatment.
Secondary outcome
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.
Background summary
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.
We 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.
Study objective
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 burden and risks
Patients will be intravenously injected at 3 time points with 37MBq, this
results in a cumulative radiation dose of 54 mSv . Some patients will have
their scans with a PET/CT camera, this results in an additional radiation dose
of 1.5 mSv per scan (total dose 58.5 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.
Postbus 30.001
9700 RB Groningen
NL
Postbus 30.001
9700 RB Groningen
NL
Listed location countries
Age
Inclusion criteria
•metastatic renal cell cancer with
•Intention to start treatment with everolimus
•WHO performance score <= 2
•measurable disease with x-ray or CT scan, at least one site of disease must be unidimensionally measurable as follows:
X-ray > 20 mm
Spiral CT scan > 10 mm
Non-spiral CT scan > 20 mm
•>= 18 years
•not pregnant or nursing
•women of childbearing potential must use effective contraception
•absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
•before patient randomization, written informed consent must be given according to GCP, and local regulations
Exclusion criteria
Are formulated as "no existence of"in inclusion criteria
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 | EUCTR2009-014257-32-NL |
| ClinicalTrials.gov | NCT01028638 |
| CCMO | NL28799.042.09 |