Primary objectivesDetermine the effect of Sorafenib (Bay 43-9006) on the uptake of In-111 labeled chimeric monoclonal antibody G250 (In-111-cG250) by RCC lesions.Determine the effect of Sorafenib (Bay 43-9006) on the uptake of In-111 labeled…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective
To determine the effect of sorafenib treatment on In-111-cG250 uptake of the
tumor
To determine the effect of sorafenib treatment on In-111-bevacizumab uptake of
the tumor
Secondary outcome
Secondary objective
Immunohistochemical analysis of CA-IX expression, (p)VHL status, HIF1-a, VEGF
and PDGF expression, apoptosis and necrosis of surgical specimen, to
investigate whether the clinical effect of sorafenib is based on angiogenesis,
or if other mechanisms play a role.
Background summary
Sorafenib is one the new drugs developed to interfere in the growth factor
signal transduction in tumors. It inhibites the ras/raf kinase pathway and VEGF
and PDGF receptors. In this way, it stops tumorcell proliferation as well as
angiogenesis.
Antiangiogenic compounds appear to be able to decrease the tumor microvascular
density (TMD) and interstitial fluid pressure (IFP), suggestive for
normalization of tumor vasculature. Normalization of tumor vasculature is
correlated with a reduction of hypoxia and IFP and as a result of this, higher
efficacy of radiotherapy and improved drug delivery to the tumor.
The monoclonal antibody cG250 has been extensively investigated in our
institute, it recognizes the HIF-inducible gene product CA-IX ubiquitously
expressed in clear cell Renal Cell Carcinoma (ccRCC). Multiple studies have
convincingly demonstrated the ability of radiolabeled cG250 to effectively
image tumors in vivo.
Bevacizumab is a humanized monoclonal anti-VEGF antibody. It depletes VEGF from
plasma, thereby inhibiting angiogenesis. Recently, radiolabeled bevacizumab has
been shown to visualise ccRCC in vivo.
Surgically excised tumor tissue will be analysed morphologically, molecularly,
(immuno)histochemically for different markers in ccRCC
This will be correlated to the radioimmunoscintigraphy.
Hypothesis:
We aim to explore the effect of sorafenib on tumor G250/CAIX and VEGF
expression, by determining the tumoral uptake of In-111 labeled G250, In-111
labeled bevacizumab. These images can be compared to the histologically
analysed surgical specimen and may lead to a better understanding of the mode
of action of sorafenib.
Study objective
Primary objectives
Determine the effect of Sorafenib (Bay 43-9006) on the uptake of In-111
labeled chimeric monoclonal antibody G250 (In-111-cG250) by RCC lesions.
Determine the effect of Sorafenib (Bay 43-9006) on the uptake of In-111
labeled bevacizumab (In-111-bevacizumab) by RCC lesions.
Secondary objectives
Increase the understanding in the mode of action of Sorafenib (Bay 43-9006) on
a histological level.
Study design
Pilot study, single center, with a sequential enrollment of patients: first 10
patients will recieve Indium labeled cG250 and the next 10 patients will
recieve Indium labeled bevacizumab.
Intervention
20 patients:
All patients will undergo two PET-scans and will take from week 2-5 every day
400mg sorafenib orally.
10 patients will recieve 200 MBq/10 mg 111In-cG250 in 50 ml isotonic saline/5 %
Human serum albumin (HAS) as a continuous intravenous (iv.) infusion in 10
minutes, after which on day 2-4 and on day 5-7 gammascans will be made.
This will happen in week 1 and in week 5.
10 patients will recieve 200 MBq/1 mg 111In-bevacizumab in 50 ml isotonic
saline/5 % Human serum albumin (HAS) as a continuous intravenous (iv.) infusion
in 10 minutes, after which on day 2-4 and on day 5-7 gammascans will be made.
This will happen in week 1 and in week 5.
Study burden and risks
Burden of the studie comprises of:
-Week 0: screening, extensive anamnesis en physical examination, EKG, blood test
-Week 1: Indium-cG250/bevacizumab injection (day 1), two scans (day 1 and day
5-7)
-Week 1: After last scan; consultation with investigator, start sorafenib
treatment
-Week 2-5: Daily use of 400mg sorafenib
-Week 4: screening side-effects sorafenib
-Week 5: Indium-cG250/bevacizumab injection (day 1), two scans (day 1 and day
5-7)
-Week 5: After last scan; stop sorafenib treatment
-Week 12: follow-up visit with investigator
Geert Grooteplein-Zuid 10
6525 GA Nijmegen
Nederland
Geert Grooteplein-Zuid 10
6525 GA Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
-Renal cell carcinoma patients planned for surgery (nephrectomy/metastectomy)
-Karnofsky > 60 %
-age over 18 years
-signed informed consent
Exclusion criteria
-Known subtype other than clear cell RCC
-Pre-exposure to murine/chimeric antibody therapy
-Chemotherapy, immunotherapy or radiation therapy within 4 weeks prior to start of study. Palliative limited field external radiation for fracture prevention is allowed
-Diabetes Mellitus
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 |
|---|---|
| Other | - |
| EudraCT | EUCTR2006-006833-42-NL |
| CCMO | NL14551.091.07 |