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Effect op Sorafenib on ccRCC Uptake of Radiolabeled Bevacizumab or cG250

This study is currently recruiting participants.
Verified February 2012 by Radboud University
Sponsor:
Collaborator:
Dutch Cancer Society
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT00602862
First received: January 3, 2008
Last updated: February 22, 2012
Last verified: February 2012
History of Changes
  Purpose

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.


Condition Intervention
Clear Cell Renal Cell Carcinoma
 Drug: Sorafenib
Drug: 111Indium-bevacizumab
Drug: 111Indium-cG250

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Effect of Sorafenib (Nexavar®) on 111-Indium Labeled Chimeric Monoclonal Antibody G250 or 111-Indium Labeled Bevacizumab (Avastin®) Uptake in Patients With Clear Cell RCC (ccRCC)

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome Measures:
  • To determine the effect of sorafenib treatment on 111In-cG250 uptake of the tumor [ Time Frame: pre-surgery ] [ Designated as safety issue: No ]
  • To determine the effect of sorafenib treatment on 111In-bevacizumab uptake of the tumor [ Time Frame: pre-surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immunohistochemical analysis of CA-IX expression, (p)VHL status, HIF1-a, VEGF and PDGF expression, apoptosis and necrosis of surgical specimen [ Time Frame: within 6 months post-surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: July 2007
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
10 Patients planned to undergo (partial) nephrectomy or metastasectomy receive an iv injection of 100 MBq/1mg 111In-Bevacizumab. Patients are then treated with Sorafenib 200 mg 2dd2 po for 4 weeks. In the last week of treatment, the same injection is given to determine tumor accumulation of the radiolabeled mAb after Sorafenib treatment. Whole-body scintigraphic images are recorded 1 week after both injections to calculate tumor uptake. After Sorafenib treatment, patients will undergo surgery.
 Drug: Sorafenib
Sorafenib 200 mg 2dd2 po for 4 weeks before surgery
Other Names:
  • Bevacizumab
  • Avastin
  • Sorafenib
  • Nexavar
  • cG250
  • Rencarex
Drug: 111Indium-bevacizumab
100 MBq / 1 mg 111Indium/bevacizumab iv
Other Names:
  • avastin
  • indium
Experimental: 2
10 Patients planned to undergo (partial) nephrectomy or metastasectomy receive an iv injection of 100 MBq/10mg 111In-cG250. Patients are then treated with Sorafenib 200 mg 2dd2 po for 4 weeks. In the last week of treatment, the same injection is given to determine tumor accumulation of the radiolabeled mAb after Sorafenib treatment. Whole-body scintigraphic images are recorded 1 week after both injections to calculate tumor uptake. After Sorafenib treatment, patients will undergo surgery.
 Drug: Sorafenib
Sorafenib 200 mg 2dd2 po for 4 weeks before surgery
Other Names:
  • Bevacizumab
  • Avastin
  • Sorafenib
  • Nexavar
  • cG250
  • Rencarex
Drug: 111Indium-cG250
100 MBq / 10 mg 111Indium-cG250 iv
Other Names:
  • rencarex
  • indium
Active Comparator: 3
5 Patients planned to undergo (partial) nephrectomy or metastasectomy receive an iv injection of 100 MBq/1mg 111In-Bevacizumab. Whole-body scintigraphic images are recorded 1 week after the injection to calculate tumor uptake. Hereafter, patients will undergo surgery.
 Drug: 111Indium-bevacizumab
100 MBq / 1 mg 111Indium/bevacizumab iv
Other Names:
  • avastin
  • indium

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 anti-arrythmics (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 tranferase inhibitors
  • Prior use of Bevacizumab and all other drugs that target VEGF/ VEGF-receptors
  • Use of anti-epileptic drugs
  • Pregnancy and lactation
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00602862

Contacts
Contact: WJG Oyen, MD, PhD +31(24)3614048 w.oyen@nucmed.umcn.nl
Contact: PFA Mulders, MD, PhD +31(24)3614048 p.mulders@uro.umcn.nl

Locations
Netherlands
Radboud University Nijmegen Medical Center Recruiting
Nijmegen, Gelderland, Netherlands, 6500 HB
Principal Investigator: WJG Oyen, MD, PhD            
Principal Investigator: PFA Mulders, MD, PhD            
Sub-Investigator: OC Boerman, PhD            
Sub-Investigator: E Oosterwijk, PhD            
Sub-Investigator: AB Stillebroer, MD            
Sponsors and Collaborators
Radboud University
Dutch Cancer Society
Investigators
Principal Investigator: WJG Oyen, MD, PhD Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Principal Investigator: PFA Mulders, MD, PhD Department of Urology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
  More Information

No publications provided by Radboud University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT00602862     History of Changes
Other Study ID Numbers: Sorafenib-mAbs
Study First Received: January 3, 2008
Last Updated: February 22, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
Angiogenesis inhibitors

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Angiogenesis Inhibitors
 Bevacizumab
Sorafenib
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013