Effect of Sorafenib on ccRCC Uptake of Radiolabeled Bevacizumab or cG250
Information source: Radboud University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Clear Cell Renal Cell Carcinoma
Intervention: Sorafenib (Drug); 111Indium-bevacizumab (Drug); 111Indium-cG250 (Drug)
Phase: N/A
Status: Completed
Sponsored by: Radboud University Official(s) and/or principal investigator(s): WJG Oyen, MD, PhD, Principal Investigator, Affiliation: Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands PFA Mulders, MD, PhD, Principal Investigator, Affiliation: Department of Urology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Summary
Sorafenib is a tyrosine kinase inhibitor that is registered for the treatment of
metastasized clear cell Renal Cell Carcinoma (ccRCC). It inhibits signal transduction of the
Vascular Endothelial Growth Factor Receptor (VEGFR) and the Platelet Derived Growth Factor
Receptor (PDGFR). In the tumorigenesis of ccRCC, VEGF and PDGF are upregulated due to the
defective Von-Hippel-Lindau (VHL) gene. CcRCC has a high Interstitial Fluid Pressure (IFP)
and Tumor Microvascular Density (TMD), hampering the delivery of chemotherapeutics and
monoclonal antibodies (mAbs). It was hypothesized that antiangiogenic compounds decrease
tumor IFP and TMD, thus normalizing tumor vasculature, before diminishing tumor vasculature.
Bevacizumab is an anti-VEGF mAb which depletes soluble VEGF from plasma, depriving VEGFR of
its ligand. Chimeric monoclonal antibody cG250 recognizes carbonic anhydrase IX (CAIX), an
antigen that is abundantly expressed in Renal Cell Carcinoma (RCC) and has limited
expression in normal tissue. The aim of this study was to investigate the effect of
Sorafenib on ccRCC physiology, by determining tumor uptake of 111In labeled cG250 or 111In
labeled Bevacizumab.
Clinical Details
Official title: The Effect of Sorafenib (NexavarŽ) on 111-Indium Labeled Chimeric Monoclonal Antibody G250 or 111-Indium Labeled Bevacizumab (AvastinŽ) Uptake in Patients With Clear Cell RCC (ccRCC)
Study design: Allocation: Non-Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: To determine the effect of sorafenib treatment on 111In-cG250 uptake of the tumorTo determine the effect of sorafenib treatment on 111In-bevacizumab uptake of the tumor
Secondary outcome: Immunohistochemical analysis of CA-IX expression, (p)VHL status, HIF1-a, VEGF and PDGF expression, apoptosis and necrosis of surgical specimen
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Renal cell carcinoma patients planned for surgery (nephrectomy/metastasectomy)
- Karnofsky > 70 %
- Laboratory values within 14 days prior to start:
- White blood cells (WBC) > 3. 5 x 109/L
- Platelets > 100 x 109/L
- Hemoglobin > 6 mmol/L
- Total bilirubin < 1. 5 upper limit of normal (ULN)
- ASAT, ALAT < 2. 5 x ULN (<5 x in case of liver metastases)
- Lactate dehydrogenase (LDH) > 1. 5. ULN
- Serum creatinine < 2 x ULN
- Amylase and Lipase < 1. 5 ULN
- Negative pregnancy test in premenopausal women
- Age over 18 years
- Signed informed consent
- Life expectancy > 24 weeks
- PT/APTT/ INR < 1. 5 ULN
- No current use of coumarin derivatives
Exclusion Criteria:
- Known subtype other than clear cell RCC
- Pre-exposure to murine/chimeric antibody therapy
- Known brain metastases
- Untreated hypercalcemia
- Uncontrolled hypertension
- Concurrent therapeutic anticoagulation
- Chemotherapy, immunotherapy or radiation therapy within 4 weeks prior to start of
study. Palliative limited field external radiation for fracture prevention is allowed
- Cardiac arrhythmias requiring antiarrhythmics (beta-blockers, digoxin), symptomatic
coronary artery disease and congestive heart failure New York Heart Association III
or IV.
- Previous malignancy < 2 years prior to the study (except for cervical carcinoma in
situ, basal cell carcinoma, or superficial bladder tumours (Ta, Tis, T1)
- Any medical condition present that in the opinion of the investigator will affect
patients' clinical status. No other concurrent malignancy except nonmetastatic
nonmelanoma skin cancer or carcinoma in situ of the cervix.
- Active clinically serious bacterial or fungal infections (< grade 2 NCI-CTC version
3)
- Known history of Human Immunodeficiency virus (HIV) infection or chronic hepatitis
B/C.
- Prior use of Raf-kinase inhibitors, MEK and Farnesyl transferase inhibitors
- Prior use of Bevacizumab and all other drugs that target VEGF/ VEGF-receptors
- Use of antiepileptic drugs
- Pregnancy and lactation
Locations and Contacts
Radboud University Nijmegen Medical Center, Nijmegen, Gelderland 6500 HB, Netherlands
Additional Information
Starting date: July 2007
Last updated: November 29, 2013
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