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NCT Number: NCT00602862

Effect of Sorafenib on ccRCC Uptake of Radiolabeled Bevacizumab or cG250

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.

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Key information

Conditions

Clear Cell Renal Cell Carcinoma Adenocarcinoma Carcinoma Carcinoma, Renal Cell Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Radboud University Nijmegen Medical Center

Nijmegen, Gelderland, 6500 HB, Netherlands

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sorafenib

Drug

Sorafenib 200 mg 2dd2 po for 4 weeks before surgery

Other names: Bevacizumab, Avastin, Nexavar, cG250, Rencarex

111Indium-bevacizumab

Drug

100 MBq / 1 mg 111Indium/bevacizumab iv

Other names: avastin, indium

111Indium-cG250

Drug

100 MBq / 10 mg 111Indium-cG250 iv

Other names: rencarex, indium

Primary outcomes

  1. To determine the effect of sorafenib treatment on 111In-cG250 uptake of the tumor

    Time frame: pre-surgery

  2. To determine the effect of sorafenib treatment on 111In-bevacizumab uptake of the tumor

    Time frame: pre-surgery

Secondary outcomes

  1. 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

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Collaborators

  • Dutch Cancer Society

Registry information

Official study 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)

Important dates

Study start
2007
Primary completion
2012
Study completion
2012
First posted
Jan 28, 2008
Registry last updated
Dec 2, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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