Effect of Sorafenib on ccRCC Uptake of Radiolabeled Bevacizumab or cG250
Clear Cell Renal Cell Carcinoma
About this trial
This is an interventional basic science trial for Clear Cell Renal Cell Carcinoma focused on measuring Angiogenesis inhibitors
Eligibility 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
Sites / Locations
- Radboud University Nijmegen Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
1
2
3
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.
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.
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.