The primary objective of the study is to evaluate the feasibility of 89Zr-bevacizumab PET imaging as a biomarker before and during treatment with sunitinib or bevacizumab plus interferon in patients with RCC.
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the change in SUVmax between baseline 89Zr-bevacizumab
PET scan and the scan performed after 2 and 6 weeks of treatment with sunitinib
or bevacizumab plus interferon in patients with RCC.
Secondary outcome
The secondary endpoint is progressive disease according to Response Evaluation
Criteria in Solid Tumors (RECIST) criteria, after 3 months of treatment.
Background summary
The majority of renal cell carcinomas is characterized by profound angiogenesis
because of inactivation of the Von Hippel Lindau gene. Treatment with
angiogenesis inhibitors results in doubling of progression free survival in the
metastatic setting.
Currently it is not possible to predict which individual patient will benefit
from anti-angiogenic therapy. A predictive biomarker for efficacy of
angiogenesis inhibitors is urgently needed as it may spare the patients
unnecessary side effects, safes costs for the society as angiogenesis
inhibitors are expensive agents and for research purposes, a predictive
biomarker may speed up development of combination therapies, of individual
titration of the dose, and save time and patients during early clinical studies
of new agents. Angiogenesis inhibitors may fail because 1) the target for the
drug is absent, 2) the drug does not reach the target or 3) angiogenesis is not
sufficiently inhibited. Serum VEGF increases abruptly after start sunitinib
while free serum VEGF decreases after start bevacizumab, a phenomenon that is
not understood and may not reflect tumour VEGF production. Non-invasive
measurement of VEGF in the tumour and its surroundings by 89Zr-bevacizumab
labelled PET imaging can potentially give insight in presence of the target for
bevacizumab and tumour dependency on angiogenesis. Change in 89Zr-bevacizumab
uptake early during treatment with angiogenesis inhibitors may be a predicitive
biomarker for clinical benefit.
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
sunitinib or bevacizumab plus interferon in patients with RCC.
Study design
This is a pilot study for evaluation of 89Zr-bevacizumab PET imaging as a
biomarker during treatment with sunitinib or bevacizumab plus interferon in
patients with RCC.
Patients who will start treatment with:
arm A: sunitinib 50 mg orally once daily for 28 days followed by 14 days rest,
or
arm B: bevacizumab intravenously (IV) 10 mg/kg q 14 days in combination with
IFNα2a subcutaneously (SC) 9MIU 3 times a week, are eligible for this study.
89Zr-bevacizumab PET imaging will be performed before start of treatment and
after 2 and 6 weeks of treatment.
The primary endpoint is change in SUVmax between the baseline scan and the scan
after 2 and after 6 weeks.
Patients will be injected intravenously with 37 MBq, protein dose 1-10 mg
89Zr-bevacizumab at day -4 or -3, at day 10 or 11 and at day 38 or 39.
Subsequently, images will be made at day 1, day 15 and day 43, on these days
blood will be drawn for determination of VEGF related biomarkers.
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 for female patients and 45 mSv
for male patients. 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 at 3 time points.
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
•locally advanced irresectable or metastatic renal cell cancer
•no untreated brain metastases (CT or MRI not necessary in the absence of symptoms)
•no uncontrolled hypertension
•no clinically significant cardiovascular events or disease during the last 12 months
•no surgery in the last 4 weeks
•no treatment with bevacizumab or another monoclonal antibody with anti-angiogenic properties in the last 4 months
•no treatment with a tyrosine kinase inhibitor during the last 4 weeks
•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
•clear cell histology component
•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 | EUCTR2008-005519-17-NL |
| ClinicalTrials.gov | NCT00831857 |
| CCMO | NL24452.042.08 |